Metformin and/or Clomiphene Do Not Adversely Affect Liver or Renal Function in Women with Polycystic Ovary Syndrome

PubMed Central

Aubuchon, Mira; Kunselman, Allen R.; Schlaff, William D.; Diamond, Michael P.; Coutifaris, Christos; Carson, Sandra A.; Steinkampf, Michael P.; Carr, Bruce R.; McGovern, Peter G.; Cataldo, Nicholas A.; Gosman, Gabriella G.; Nestler, John E.; Myers, Evan R.

2011-01-01

Context: Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function. Objective: We sought to determine the effects of MET on serum hepatic parameters in PCOS patients. Design: This was a secondary analysis of a randomized, doubled-blind trial from 2002–2004. Setting: This multi-center clinical trial was conducted in academic centers. Patients: Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included. Interventions: Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months. Main Outcome Measure: The percent change from baseline in renal and liver function between- and within-treatment arms was assessed. Results: Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, −14.7 to −21.3%) as well as creatinine (−4.2 to −6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (−10% in bilirubin, −9 to −11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm. Conclusion: Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function. PMID:21832111

Comparative effectiveness of liver transplant strategies for end-stage liver disease patients on renal replacement therapy.

PubMed

Chang, Yaojen; Gallon, Lorenzo; Jay, Colleen; Shetty, Kirti; Ho, Bing; Levitsky, Josh; Baker, Talia; Ladner, Daniela; Friedewald, John; Abecassis, Michael; Hazen, Gordon; Skaro, Anton I

2014-09-01

There are complex risk-benefit tradeoffs with different transplantation strategies for end-stage liver disease patients on renal support. Using a Markov discrete-time state transition model, we compared survival for this group with 3 strategies: simultaneous liver-kidney (SLK) transplantation, liver transplantation alone (LTA) followed by immediate kidney transplantation if renal function did not recover, and LTA followed by placement on the kidney transplant wait list. Patients were followed for 30 years from the age of 50 years. The probabilities of events were synthesized from population data and clinical trials according to Model for End-Stage Liver Disease (MELD) scores (21-30 and >30) to estimate input parameters. Sensitivity analyses tested the impact of uncertainty on survival. Overall, the highest survival rates were seen with SLK transplantation for both MELD score groups (82.8% for MELD scores of 21-30 and 82.5% for MELD scores > 30 at 1 year), albeit at the cost of using kidneys that might not be needed. Liver transplantation followed by kidney transplantation led to higher survival rates (77.3% and 76.4%, respectively, at 1 year) than placement on the kidney transplant wait list (75.1% and 74.3%, respectively, at 1 year). When uncertainty was considered, the results indicated that the waiting time and renal recovery affected conclusions about survival after SLK transplantation and liver transplantation, respectively. The subgroups with the longest durations of pretransplant renal replacement therapy and highest MELD scores had the largest absolute increases in survival with SLK transplantation versus sequential transplantation. In conclusion, the findings demonstrate the inherent tension in choices about the use of available kidneys and suggest that performing liver transplantation and using renal transplantation only for those who fail to recover their native renal function could free up available donor kidneys. These results could inform discussions about transplantation policy. © 2014 American Association for the Study of Liver Diseases.

Successful treatment of donor-derived hepatitis C viral infection in three transplant recipients from a donor at increased risk for bloodborne pathogens.

PubMed

Shah, Ashesh P; Cameron, Andrew; Singh, Pooja; Frank, Adam M; Fenkel, Jonathan M

2017-04-01

We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)-negative donor to three HCV-negative recipients-two renal transplants and one liver. Both renal recipients underwent standard deceased-donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39-year-old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV-infected male partner. Recipient 1 was a 45-year-old man with a history of end-stage renal disease from systemic lupus erythematosus. Recipient 2 was a 62-year-old woman with a history of end-stage renal disease caused by hypertension and insulin-dependent diabetes. Recipient 3 was a 42-year-old man with acute liver failure from acetaminophen ingestion. All recipients became HCV polymerase chain reaction positive on post-transplant follow-up. Both kidney recipients were treated with ledipasvir/sofosbuvir combination therapy for 12 weeks without side effects or rejection episodes. Recipient 3 was treated with ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks without side effects. All patients achieved a sustained viral response at 12 weeks and are considered cured of HCV. The kidney recipients maintained good allograft function with a serum creatinine of 1.4 mg/dL and 1.0 mg/dL, respectively. Both renal recipients maintained normal liver function post treatment and did not develop any evidence of fibrosis. The liver recipient's liver function tests returned to normal without further incident. This case report provides evidence for the successful treatment of donor-derived HCV in transplant recipients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hepatic steatosis and non-alcoholic fatty liver disease are not associated with decline in renal function in people with Type 2 diabetes.

PubMed

Jenks, S J; Conway, B R; Hor, T J; Williamson, R M; McLachlan, S; Robertson, C; Morling, J R; Strachan, M W J; Price, J F

2014-09-01

We aimed to determine whether the presence of hepatic steatosis and/or non-alcoholic fatty liver disease was associated with decline in renal function or onset of microalbuminuria in a cohort of people with Type 2 diabetes, including those managed in both primary and secondary care. Nine hundred and thirty-three patients from the Edinburgh Type 2 Diabetes Study, a cohort of Scottish men and women aged 60-74 years with Type 2 diabetes, underwent assessment for hepatic steatosis by liver ultrasonography 1 year after recruitment. Non-alcoholic fatty liver disease was defined as the presence of steatosis following exclusion of secondary causes of liver disease. Patients were followed for 4 years and decline in renal function was assessed by the change in estimated glomerular filtration rate over time. Of the 933 subjects, 530 had hepatic steatosis and, of those with hepatic steatosis, 388 had non-alcoholic fatty liver disease. Neither hepatic steatosis nor non-alcoholic fatty liver disease were significantly associated with rate of decline in renal function, with the mean rate of decline in estimated glomerular filtration rate being -1.55 ml min(-1) 1.73 m(-2) per year for participants with hepatic steatosis compared with -1.84 ml min(-1) 1.73 m(-2) for those without steatosis (P = 0.19). Similar results were obtained when the analysis was restricted to participants with and without non-alcoholic fatty liver disease (-1.44 vs. -1.64 ml min(-1) 1.73 m(-2) per year, respectively; P = 0.44). Additionally, neither hepatic steatosis nor non-alcoholic fatty liver disease were associated with the onset or regression of albuminuria during follow-up (all P ≥ 0.05). The presence of hepatic steatosis/non-alcoholic fatty liver disease was not associated with decline in renal function during a 4-year follow-up in our cohort of older people with Type 2 diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Assessing renal function with daclizumab induction and delayed tacrolimus introduction in liver transplant recipients.

PubMed

Calmus, Yvon; Kamar, Nassim; Gugenheim, Jean; Duvoux, Christophe; Ducerf, Christian; Wolf, Philippe; Samuel, Didier; Vanlemmens, Claire; Neau-Cransac, Martine; Salamé, Ephrem; Chazouillères, Olivier; Declerck, Nicole; Pageaux, Georges-Philippe; Dubel, Laurence; Rostaing, Lionel

2010-06-27

Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection. This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 micromol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 micrommol/L at 6 months. The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (100 micromol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 micromol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time. Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline.

Acute kidney injury in acute liver failure: a review.

PubMed

Moore, Joanna K; Love, Eleanor; Craig, Darren G; Hayes, Peter C; Simpson, Kenneth J

2013-11-01

Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.

Renal dysfunction in liver cirrhosis and its correlation with Child-Pugh score and MELD score

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Gurning, M.

2018-03-01

Renal dysfunction (RD) is a serious and common complication in a patient with liver cirrhosis. It provides a poor prognosis. The aim of our study was to evaluate the renal function in liver cirrhosis, also to determine the correlation with the graduation of liver disease assessed by Child-Pugh Score (CPS) and MELD score. This was a cross-sectional study included patients with liver cirrhosis admitted to Adam Malik Hospital Medan in June - August 2016. We divided them into two groups as not having renal dysfunction (serum creatinine < 1.5 mg/dL) and having renal dysfunction (serum creatinine ≤ 1.5 mg/dL). For the processing of data, SPSS 22.0 was used. Statistical methods used: Chi-square, Fisher exact, one way ANOVA, Kruskal Wallis test and Pearson coefficient of correlation. The level of significance was p<0.05. 55 patients with presented with renal dysfunction were 16 (29.1 %). There was statistically significant inverse correlation between GFR and CPS (r = -0.308), GFR and MELD score (r = -0.278). There was a statistically significant correlation between creatinine and MELD score (r = 0.359), creatinine and CPS (r = 0.382). The increase of the degree of liver damage is related to the increase of renal dysfunction.

Kidney allocation to liver transplant candidates with renal failure of undetermined etiology: role of percutaneous renal biopsy.

PubMed

Wadei, H M; Geiger, X J; Cortese, C; Mai, M L; Kramer, D J; Rosser, B G; Keaveny, A P; Willingham, D L; Ahsan, N; Gonwa, T A

2008-12-01

The feasibility, value and risk of percutaneous renal biopsy (PRB) in liver transplant candidates with renal failure are unknown. PRB was performed on 44 liver transplant candidates with renal failure of undetermined etiology and glomerular filtration rate (GFR) <40 mL/min/1.73 m(2) (n = 37) or on renal replacement therapy (RRT) (n = 7). Patients with >or=30% interstitial fibrosis (IF), >or=40% global glomerulosclerosis (gGS) and/or diffuse glomerulonephritis were approved for simultaneous-liver-kidney (SLK) transplantation. Prebiopsy GFR, urinary sodium indices, dependency on RRT and kidney size were comparable between 27 liver-transplant-alone (LTA) and 17 SLK candidates and did not relate to the biopsy diagnosis. The interobserver agreement for the degree of IF or gGS was moderate-to-excellent. After a mean of 78 +/- 67 days, 16 and 8 patients received LTA and SLK transplants. All five LTA recipients on RRT recovered kidney function after transplantation and serum creatinine was comparable between LTA and SLK recipients at last follow-up. Biopsy complications developed in 13, of these, five required intervention. PRB is feasible in liver transplant candidates with renal failure and provides reproducible histological information that does not relate to the pretransplant clinical data. Randomized studies are needed to determine if PRB can direct kidney allocation in this challenging group of liver transplant candidates.

Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes

PubMed Central

Chen, Chee Keong; Mohamad, Wan Mohd Zahiruddin Wan; Ooi, Foong Kiew; Ismail, Shaiful Bahari; Abdullah, Mohamad Rusli; George, Annie

2014-01-01

Background: Eurycoma longifolia Jack (ElJ) has been shown to elevate serum testosterone and increased muscle strength in humans. This study investigated the effects of Physta® a standardized water extract of ElJ (400 mg/day for 6 weeks) on testosterone: epitestosterone (T:E) ratio, liver and renal functions in male recreational athletes. Methods: A total of 13 healthy male recreational athletes were recruited in this double blind, placebo-controlled, cross-over study. The participants were required to consume either 400 mg of ElJ or placebo daily for 6 weeks in the first supplementation regimen. Following a 3 week wash-out period, the participants were requested to consume the other supplement for another 6 weeks. Mid-stream urine samples and blood samples were collected prior to and after 6 weeks of supplementation with either ElJ or placebo. The urine samples were subsequently analyzed for T:E ratio while the blood samples were analyzed for liver and renal functions. Results: T:E ratio was not significantly different following 6 weeks supplementation of either ElJ or placebo compared with their respective baseline values. Similarly, there were no significant changes in both the liver and renal functions tests following the supplementation of ElJ. Conclusions: Supplementation of ElJ i.e. Physta® at a dosage of 400 mg/day for 6 weeks did not affect the urinary T:E ratio and hence will not breach any doping policies of the International Olympic Committee for administration of exogenous testosterone or its precursor. In addition, the supplementation of ElJ at this dosage and duration was safe as it did adversely affect the liver and renal functions. PMID:25013692

New Developments in Hepatorenal Syndrome.

PubMed

Mindikoglu, Ayse L; Pappas, Stephen C

2018-02-01

Hepatorenal syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis, leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain because of the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal dysfunction. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to estimate measured GFR more accurately. A major change in the diagnostic criteria for HRS based on dynamic serial changes in serum Cr that regard HRS type 1 as a special form of acute kidney injury promises the possibility of earlier identification of renal dysfunction in patients with cirrhosis. The diagnostic criteria of HRS still include the exclusion of other causes of kidney injury. Renal biomarkers have been disappointing in assisting with the differentiation of HRS from prerenal azotemia and other kidney disorders. Serum metabolomic profiling may be a more powerful tool to assess renal dysfunction, although the practical clinical significance of this remains unclear. As a result of the difficulties of assessing renal function in cirrhosis and the varying HRS diagnostic criteria and the rigor with which they are applied, the precise incidence and prevalence of HRS is unknown, but it is likely that HRS occurs more commonly than expected. The pathophysiology of HRS is rooted firmly in the setting of progressive reduction in renal blood flow as a result of portal hypertension and splanchnic vasodilation. Progressive marked renal cortical ischemia in patients with cirrhosis parallels the evolution of diuretic-sensitive ascites to diuretic-refractory ascites and HRS, a recognized continuum of renal dysfunction in cirrhosis. Alterations in nitrous oxide production, both increased and decreased, may play a major role in the pathophysiology of this evolution. The inflammatory cascade, triggered by bacterial translocation and endotoxemia, increasingly recognized as important in the manifestation of acute-on-chronic liver failure, also may play a significant role in the pathophysiology of HRS. The mainstay of treatment remains vasopressor therapy with albumin in an attempt to reverse splanchnic vasodilation and improve renal blood flow. Several meta-analyses have confirmed the value of vasopressors, chiefly terlipressin and noradrenaline, in improving renal function and reversing HRS type 1. Other interventions such as renal replacement therapy, transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Liver transplantation remains the definitive treatment for HRS. The frequency of simultaneous liver-kidney transplantation has increased dramatically in the Model for End-stage Liver Disease era, with changes in organ allocation policies. This has resulted in a more urgent need to predict native kidney recovery from HRS after liver transplantation alone, to avoid unnecessary simultaneous liver-kidney transplantation. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence

PubMed Central

Klintmalm, Goran B.; Nashan, Björn

2014-01-01

Despite the success of liver transplantation, long-term complications remain, including de novo malignancies, metabolic syndrome, and the recurrence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). The current mainstay of treatment, calcineurin inhibitors (CNIs), can also worsen posttransplant renal dysfunction, neurotoxicity, and diabetes. Clearly there is a need for better immunosuppressive agents that maintain similar rates of efficacy and renal function whilst minimizing adverse effects. The mammalian target of rapamycin (mTOR) inhibitors with a mechanism of action that is different from other immunosuppressive agents has the potential to address some of these issues. In this review we surveyed the literature for reports of the use of mTOR inhibitors in adult liver transplantation with respect to renal function, efficacy, safety, neurological symptoms, de novo tumors, and the recurrence of HCC and HCV. The results of our review indicate that mTOR inhibitors are associated with efficacy comparable to CNIs while having benefits on renal function in liver transplantation. We also consider newer dosing schedules that may limit side effects. Finally, we discuss evidence that mTOR inhibitors may have benefits in the oncology setting and in relation to HCV-related allograft fibrosis, metabolic syndrome, and neurotoxicity. PMID:24719752

Temporary Intraoperative Porto-Caval Shunts in Piggy-Back Liver Transplantation Reduce Intraoperative Blood Loss and Improve Postoperative Transaminases and Renal Function: A Meta-Analysis.

PubMed

Pratschke, Sebastian; Rauch, Alexandra; Albertsmeier, Markus; Rentsch, Markus; Kirschneck, Michaela; Andrassy, Joachim; Thomas, Michael; Hartwig, Werner; Figueras, Joan; Del Rio Martin, Juan; De Ruvo, Nicola; Werner, Jens; Guba, Markus; Weniger, Maximilian; Angele, Martin K

2016-12-01

The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation. A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2 ) were also utilized. Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery. This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

Effect and Outcome of Intraoperative Fluid Restriction in Living Liver Donor Hepatectomy.

PubMed

Wang, Chih-Hsien; Cheng, Kwok-Wai; Chen, Chao-Long; Wu, Shao-Chun; Shih, Tsung-Hsiao; Yang, Sheng-Chun; Lee, Ying-En; Jawan, Bruno; Huang, Chiu-En; Juang, Sin-Ei; Huang, Chia-Jung

2017-11-10

BACKGROUND The purpose of this study was to evaluate the effect and outcome of intraoperative fluid restriction in living liver donor hepatectomy, regarding changes in intraoperative CVP levels, blood loss, and postoperative renal function. MATERIAL AND METHODS The charts of 167 patients were reviewed and analyzed retrospectively. Intraoperative central venous pressure levels, blood loss, fluids infused, and urine output per hour, before and after the liver allograft procurement, were calculated. Perioperative renal functions were also analyzed. RESULTS Fluid infused before and after liver allograft procurement was 3.21±1.5 and 9.0±3.9 mL/Kg/h and urine output was 1.5±0.7 and 1.8±1.4 mL/Kg/h, respectively. Intraoperative estimated blood loss was 91.3±78.9 mL. No patients required blood transfusion. Their preoperative and postoperative hemoglobin were 12.3±2.7 and 11.7±1.7 g/dL. CVP levels decreased gradually from 10.4±3.0 to a low of 8.1±1.9 mmHg at the time of transection of the liver parenchyma. Renal functions were not significantly affected based on the determination of BUN and creatinine levels. CONCLUSIONS The methods used to lower CVP are moderate and slow, with 2 main goals achieved: minimal blood loss (91.3±78.9 ml) and no blood transfusion. Furthermore, it did not have any negative effect on renal function.

A Case of Left Renal Vein Ligation in a Patient with Solitary Left Kidney Undergoing Liver Transplantation to Control Splenorenal Shunt and Improve Portal Venous Flow.

PubMed

Martino, Rodrigo B; Júnior, Eserval Rocha; Manuel, Valdano; Rocha-Santos, Vinicius; D'Albuquerque, Luis Augusto C; Andraus, Wellington

2017-10-11

BACKGROUND Adequate portal venous flow is required for successful liver transplantation. Reduced venous flow and blood flow 'steal' by collateral vessels are a concern, and when there is a prominent splenorenal shunt present, ligation of the left renal vein has been recommended to improve portal venous blood flow. CASE REPORT A 51-year-old man who had undergone right nephrectomy in childhood required liver transplantation for liver cirrhosis and hepatocellular carcinoma due to hepatitis C virus (HCV) infection. The patient had no other comorbidity and no history of hepatorenal syndrome. At transplantation surgery, portal venous flow was poor and did not improve with ligation of shunt veins, but ligation of the left renal vein improved portal venous flow. On the first and fifth postoperative days, the patient was treated with basiliximab, a chimeric monoclonal antibody to the IL-2 receptor, and methylprednisolone. The calcineurin inhibitor, tacrolimus, was introduced on the fifth postoperative day. On the sixteenth postoperative day, renal color Doppler ultrasound showed normal left renal parenchyma; hepatic Doppler ultrasound showed good portal vein flow and preserved hepatic parenchyma in the liver transplant. CONCLUSIONS This case report has shown that in a patient with a single left kidney, left renal vein ligation is feasible and safe in a patient with no other risk factors for renal impairment following liver transplantation. Modification of postoperative immunosuppression to avoid calcineurin inhibitors in the very early postoperative phase may be important in promoting good recovery of renal function and to avoid the need for postoperative renal dialysis.

Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

PubMed

Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

2015-08-28

A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

Influence of Donor and Recipient CYP3A4, CYP3A5, and ABCB1 Genotypes on Clinical Outcomes and Nephrotoxicity in Liver Transplant Recipients.

PubMed

Debette-Gratien, Marilyne; Woillard, Jean-Baptiste; Picard, Nicolas; Sebagh, Mylène; Loustaud-Ratti, Véronique; Sautereau, Denis; Samuel, Didier; Marquet, Pierre

2016-10-01

This study investigated the influence of the CYP3A4*22, CYP3A5*3, and ABCB1 exons 12, 21, and 26 polymorphisms in donors and recipients on clinical outcomes and renal function in 170 liver transplant patients on cyclosporin A (CsA) or tacrolimus (Tac). Allelic discrimination assays were used for genotyping. Multivariate time-dependent Cox proportional hazard models, multiple linear regression using the generalized estimating equation and linear mixed-effect models were used for statistical analysis. Expression of CYP3A5 by either or both the donor and the recipient was significantly associated with lower Tac, but not CsA, dose-normalized trough levels. In the whole population, graft loss was only significantly associated with longer exposure to high calcineurin inhibitor (CNI) concentrations (hazard ratio, 6.93; 95% confidence interval, 2.13-22.55), P = 0.00129), whereas in the Tac subgroup, the risk of graft loss was significantly higher in recipient CYP3A5*1 expressers (hazard ratio, 3.39; 95% confidence interval, 1.52-7.58; P = 0.0028). Renal function was significantly associated with: (1) baseline modification of diet in renal disease (β = 0.51 ± 0.05; P < 0.0001); (2) duration of patient follow-up (per visit, β = -0.98 ± 0.22; P < 0.0001); and (3) CNI exposure (per quantile increase, β = -2.42 ± 0.59; P < 0.0001). No genetic factor was associated with patient survival, acute rejection, liver function test results, recurrence of viral or other initial liver disease, or renal function. This study confirms the effect of CYP3A5*3 on tacrolimus dose requirement in liver transplantation and shows unexpected associations between the type of, and exposure to, CNI and either chronic rejection or graft loss. None of the genetic polymorphisms studied had a noticeable impact on renal function degradation at 10 years.

Acute kidney injury after liver, heart, and lung transplants: dialysis modality, predictors of renal function recovery, and impact on survival.

PubMed

Pham, Phuong-Thu T; Slavov, Carmen; Pham, Phuong-Chi T

2009-07-01

Recipients of nonrenal organ transplants including the liver, heart, and lung are at risk for developing acute kidney injury (AKI) and chronic kidney disease (CKD). Underlying hepatic or cardiopulmonary failure, prolonged intraoperative hemodynamic instability, and the use of calcineurin inhibitors and nephrotoxic medications have all been suggested to be contributory. The incidence of perioperative AKI has been reported to occur in 17% to 95% in liver transplant recipients, 5% to 30% in heart transplant recipients, and 5% to 60% in recipients of lung transplants. Among those who develop AKI, renal replacement therapy is required in 5% to 35%, 5% to 15%, and 8% to 10% in liver, heart, and lung transplant recipients, respectively. The current article presents an overview of the literature on the choice of dialysis modality and its associated advantages and disadvantages in the management of AKI after liver, heart, and lung transplants. Predictive factors for renal function recovery and the impact of AKI and CKD on survival will also be discussed.

Urinary Liver Type Fatty Acid Binding Protein Is Negatively Associated With Estimated Glomerular Filtration Rate in Renal Transplant Recipients With Graft Loss.

PubMed

Huang, Y-C; Chang, Y-S; Chen, C-C; Tsai, S-F; Yu, T-M; Wu, M-J; Chen, C-H

2018-05-01

Liver type fatty acid binding protein (L-FABP) is abundant not only in the liver but also in the kidney and is excreted in urine. Its primary function is to facilitate intracellular long chain fatty acid transport and it might also act as an endogenous antioxidant molecular. The purpose of this study was to investigate whether plasma or urinary L-FABP levels were associated with graft function in renal transplant recipients. Sixty-seven renal transplant recipients with a mean age of 48.8 years were recruited. The mean duration of renal transplantation was 4131 days. Recipients were divided into 2 groups based on their estimated glomerular filtration rate (eGFR) values: moderate graft function (eGFR ≥60 mL/min/1.73 m 2 ) and low graft function (eGFR <60 mL/min/1.73 m 2 ). Fasting plasma and urinary L-FABP levels were measured. There was no significant difference in plasma L-FABP level between the 2 groups, although recipients in the low graft function group had significantly lower urinary L-FABP level when compared with recipients in the moderate graft function group. Plasma and urinary L-FABP levels were not associated with eGFR in the 67 recipients; however, urinary L-FABP level (β = -1.24, P = .037) and level adjusted by urinary creatinine (β = -0.75, P = .046) were significantly negatively associated with eGFR in recipients with low graft function after adjusting for potential confounders. Increased urinary L-FABP level seems to be a significant indicator of decreased graft function in renal transplant recipients with loss of graft function. Copyright © 2018 Elsevier Inc. All rights reserved.

Protective effects of a natural herbal compound quercetin against snake venom-induced hepatic and renal toxicities in rats.

PubMed

Al-Asmari, Abdulrahman K; Khan, Haseeb A; Manthiri, Rajamohamed A; Al-Khlaiwi, Ahmad A; Al-Asmari, Bayan A; Ibrahim, Khalid E

2018-05-08

Echis pyramidum is a highly poisonous viper snake. Previous studies have shown acute phase hepatic and renal toxicities of Echis pyramidum venom (EPV) in rats. This study reports the protective effects of a natural herbal compound quercetin (QRC) on EPV-induced hepatic and renal toxicities in rats. A singly injection of EPV (4.76 mg/kg) caused significant increase in serum biomarkers of liver and kidney function. Pre-treatment of QRC (10 mg/kg) significantly reduced the toxic effects of EPV on functional impairment in liver and kidneys of rats. Administration of QRC also reversed EPV-induced increase in lipid peroxidation and decrease in total thiols. The histopathology of liver showed fat accumulation, focal degeneration and cytoplasmic vacuolation of hepatocytes in EPV treated rats. EPV also caused renal tubular dilation and focal atrophy of glomerular tufts in rat kidneys. Administration of QRC prevented EPV-induced structural tissue damage in liver and kidneys of rats. In conclusion, QRC significantly inhibited the acute phase toxic effects of EPV on liver and kidneys of rats by preventing the oxidative stress in these organs. QRC is also known for its anti-inflammatory, anti-edema, anti-hemorrhagic and PLA2-inhibitory properties and therefore may be regarded as a multi-action antidote against snake venom toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Early detection, prevention and management of renal failure in liver transplantation].

PubMed

Castells, Lluís; Baliellas, Carme; Bilbao, Itxarone; Cantarell, Carme; Cruzado, Josep Maria; Esforzado, Núria; García-Valdecasas, Juan Carlos; Lladó, Laura; Rimola, Antoni; Serón, Daniel; Oppenheimer, Federico

2014-10-01

Renal failure is a frequent complication in liver transplant recipients and is associated with increased morbidity and mortality. A variety of risk factors for the development of renal failure in the pre- and post-transplantation periods have been described, as well as at the time of surgery. To reduce the negative impact of renal failure in this population, an active approach is required for the identification of those patients with risk factors, the implementation of preventive strategies, and the early detection of progressive deterioration of renal function. Based on published evidence and on clinical experience, this document presents a series of recommendations on monitoring RF in LT recipients, as well as on the prevention and management of acute and chronic renal failure after LT and referral of these patients to the nephrologist. In addition, this document also provides an update of the various immunosuppressive regimens tested in this population for the prevention and control of post-transplantation deterioration of renal function. Copyright © 2013 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial.

PubMed

Nashan, Bjorn; Schemmer, Peter; Braun, Felix; Dworak, Markus; Wimmer, Peter; Schlitt, Hans

2015-03-26

Introduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients. However, long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure, neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV) infection and hepatocellular carcinoma. Several studies have shown that everolimus has the potential to provide protection against viral replication, malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy. The Hephaistos study evaluates the beneficial effects of early initiation of everolimus in de novo liver transplant recipients. Hephaistos is an ongoing 12-month, multi-center, open-label, controlled study aiming to enroll 330 de novo liver transplant recipients from 15 centers across Germany. Patients are randomized in a 1:1 ratio (7-21 days post-transplantation) to receive everolimus (trough levels 3-8 ng/mL) with reduced tacrolimus (trough levels <5 ng/mL), or standard tacrolimus (trough levels 6-10 ng/mL) after entering a run-in period (3-5 days post-transplantation). In the run-in period, patients are treated with induction therapy, mycophenolate mofetil, tacrolimus, and corticosteroids according to local practice. Randomization is stratified by HCV status and model of end-stage liver disease scores at transplantation. The primary objective of the study is to exhibit superior renal function (estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease (MDRD)-4 formula) with everolimus plus reduced tacrolimus compared to standard tacrolimus at Month 12. Other objectives are: to assess the incidence of treated biopsy-proven acute rejection, graft loss, or death; the incidences of components of the composite efficacy endpoint; renal function via estimated glomerular filtration rate using various formulae (MDRD-4, Nankivell, Cockcroft-Gault, chronic kidney disease epidemiology collaboration and Hoek formulae); the incidence of proteinuria; the incidence of adverse events and serious adverse events; the incidence and severity of cytomegalovirus and HCV infections and HCV-related fibrosis. This study aims to demonstrate superior renal function, comparable efficacy, and safety in de novo liver transplant recipients receiving everolimus with reduced tacrolimus compared with standard tacrolimus. This study also evaluates the antiviral benefit by early initiation of everolimus. NCT01551212 .

Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

PubMed

Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

2016-12-20

The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation.

PubMed

Andreoli, Maria Claudia Cruz; Souza, Nádia Karina Guimarães de; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Coelho, Maria Paula Vilela; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; Almeida, Marcio Dias de; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; Santos, Oscar Pavão Dos; Santos, Bento Cardoso Dos

2017-01-01

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less than 90 days. Therefore, a high proportion of OLT patients showed improved renal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability of recovery.

Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation

PubMed Central

de Souza, Nádia Karina Guimarães; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; de Almeida, Marcio Dias; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; dos Santos, Oscar Pavão

2017-01-01

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27–39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less than 90 days. Therefore, a high proportion of OLT patients showed improved renal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability of recovery. PMID:28574999

[Simultaneous Hepatorenal Transplantation from a Brain-Dead Donor for Graft Dysfunction and Renal Insufficiency in a Liver Transplant Recipient : A Case Report].

PubMed

Takada, Hideaki; Kobayashi, Takashi; Ogawa, Kohei; Miyata, Hitomi; Sawada, Atsuro; Akamatsu, Shusuke; Negoro, Hiromitsu; Saito, Ryoichi; Terada, Naoki; Yamasaki, Toshinari; Inoue, Takahiro; Teramoto, Yuki; Shibuya, Shinsuke; Haga, Hironori; Kaido, Toshimi; Uemoto, Shinji; Ogawa, Osamu

2017-08-01

We report a case of lethal hepatorenal insufficiency in a 52-year-old man who received successful simultaneous hepatorenal transplantation from a deceased donor. The patient had undergone live-donor liver transplantation for type-C hepatitis and liver cirrhosis 11 years before he developed graft liver dysfunction due to recurrent viral hepatitis and cirrhosis. At that instance, he also developed end-stage renal dysfunction due to calcineurin inhibitor nephropathy and hepatorenal syndrome. Although he needed three open hemostases and abundant blood transfusion, he was withdrawn from continuous hemodiafiltration on the 55th day and discharged from the hospital on the 272nd day postoperatively. Simultaneous hepatorenal transplantation was reported to be associated with more favorable outcomes of graft function, lower rejection rates, but higher perioperative complication rates compared with liver transplantation alone in patients on hemodialysis. Particularly, close attention should be paid for hemostasis since patients have a hemorrhagic tendency until the recovery of graft liver function.

Management of Renal Artery Occlusion Related to Multiple Trauma in Children: Two Case Reports.

PubMed

Xu, Guofeng; He, Lei; Fang, Xiaoliang; Jiang, Dapeng; Jin, Longhu; Lin, Houwei; Xu, Maosheng; Wu, Yeming; Geng, Hongquan

2017-03-01

We report 2 successful treatment cases of renal artery occlusion (RAO) related to multiple trauma. A 4-year-old boy was diagnosed with right RAO and liver laceration after a traffic accident. Surgical thrombectomy and revascularization were performed, but the lacerated liver was not sutured. The lacerated liver was surgically repaired 6 days post operation because of delayed bleeding. Thirteen percent of the patient's right kidney function was conserved. Another 7-year-old boy was compressed by an agitator. Renal scintigraphy showed that the right kidney was nonfunctional. The patient underwent conservative observation without any complication. In stable patients with multiple trauma, RAO should be diagnosed as soon as possible. Copyright © 2016 Elsevier Inc. All rights reserved.

Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD.

PubMed

Udi, Shiran; Hinden, Liad; Earley, Brian; Drori, Adi; Reuveni, Noa; Hadar, Rivka; Cinar, Resat; Nemirovski, Alina; Tam, Joseph

2017-12-01

Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB 1 R) induces nephropathy, whereas CB 1 R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB 1 R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β -oxidation. Collectively, these findings indicate that renal proximal tubule cell CB 1 R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway. Copyright © 2017 by the American Society of Nephrology.

Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain.

PubMed

Bilbao, Itxarone; Salcedo, Magdalena; Gómez, Miguel Angel; Jimenez, Carlos; Castroagudín, Javier; Fabregat, Joan; Almohalla, Carolina; Herrero, Ignacio; Cuervas-Mons, Valentín; Otero, Alejandra; Rubín, Angel; Miras, Manuel; Rodrigo, Juan; Serrano, Trinidad; Crespo, Gonzalo; De la Mata, Manuel; Bustamante, Javier; Gonzalez-Dieguez, M Luisa; Moreno, Antonia; Narvaez, Isidoro; Guilera, Magda

2015-08-01

A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy. © 2015 American Association for the Study of Liver Diseases.

Chlorogenic acid protects D-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice.

PubMed

Feng, Yan; Yu, Ying-Hua; Wang, Shu-Ting; Ren, Jing; Camer, Danielle; Hua, Yu-Zhou; Zhang, Qian; Huang, Jie; Xue, Dan-Lu; Zhang, Xiao-Fei; Huang, Xu-Feng; Liu, Yi

2016-01-01

Oxidative stress and inflammation are implicated in the aging process and its related hepatic and renal function decline. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the human diet. Recently, CGA has shown in vivo and in vitro antioxidant properties. The current study investigates the effects of protective effects of chlorogenic acid (CGA) on D-galactose-induced liver and kidney injury. Hepatic and renal injuries were induced in a mouse model by subcutaneously injection of D-galactose (D-gal; 100 mg/kg) once a day for 8 consecutive weeks and orally administered simultaneously with CGA included in the food (200 mg/kg of diet). The liver and renal functions were examined. Histological analyses of liver and kidney were done by haematoxylin and eosin staining. The oxidative stress markers and pro-inflammatory cytokines in the liver and the kidney were measured. Results CGA significantly reduced the serum aminotransferase, serum creatinine (SCr) and blood urea nitrogen (BUN) levels in D-gal mice (p <0.05). CGA also restored superoxide dismutase, catalase, and malondialdehyde levels and decreased glutathione content in the liver and kidney in D-gal mice (p <0.05). Improvements in liver and kidney were also noted in histopathological studies. CGA reduced tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) protein levels in the liver and kidney in D-gal mice (p <0.05). These findings suggest that CGA attenuates D-gal-induced chronic liver and kidney injury and that this protection may be due to its antioxidative and anti-inflammatory activities.

Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease

PubMed Central

Mainzer, Barbara; Lahrssen-Wiederholt, Monika; Schafft, Helmut; Palavinskas, Richard; Breithaupt, Angele; Zentek, Jürgen

2015-01-01

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations. PMID:25234328

Ascites, a New Cause for Bilateral Hydronephrosis: Case Report

PubMed Central

Jain, Deepika; Dorairajan, Smrita; Misra, Madhukar

2009-01-01

Bilateral hydronephrosis secondary to urinary obstruction leads to a buildup of back pressure in the urinary tract and may lead to impairment of renal function. We present a case of a 57-year-old male with a history of alcoholic liver cirrhosis, who presented with tense ascites and acute renal failure. Bilateral hydronephrosis was seen on abdominal ultrasound. Multiple large-volume paracenteses resulted in resolution of hydronephrosis and prompt improvement in renal function. PMID:19802498

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis.

PubMed

Facciorusso, Antonio; Amoruso, Annabianca; Neve, Viviana; Antonino, Matteo; Prete, Valentina Del; Barone, Michele

2014-11-27

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.

Serum Lipoprotein (a) Levels in Chronic Renal Failure and Liver Cirrhosis Patients. Relationship with Atherosclerosis

PubMed Central

Mady, Essam; Wissa, Gehane; Khalifa, Ali; El-Sabbagh, Mahmoud

1999-01-01

This study was carried out to investigate the relationship between lipoprotein (a) levels and the development of atherosclerosis in chronic renal failure (CRF) patients with the possible role of the liver. Serum Lp (a) levels were measured in samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (transaminases (ALT and AST), alkaline phosphatase (ALP) and total bilirubin) investigations and serum cholesterol were carried out for all the subjects enrolled in this study. Serum Lp (a) concentration in CRF patients without LC was 87.25 ± 6.17 mg/dl, which was significantly higher than all the investigated groups (P < 0.001). Lp(a) concentration in patients with both CRF and LC was 24.65 ± 1.98 mg/dl, which was not significantly different from the controls, but was significantly higher than that in the subjects with LC only (P < 0.001) where the latter group had significantly low Lp (a) values (11.1 ± 0.99) relative to all the other groups (P < 0.001). Lp (a) correlated positively with cholesterol in all groups except the LC subjects, but did not correlate with age, or renal function in both CRF groups. PMID:10689547

Exaggerated Liver Injury Induced by Renal Ischemia Reperfusion in Diabetes: Effect of Exenatide

PubMed Central

Vaghasiya, Jitendra D.; Sheth, Navin R.; Bhalodia, Yagnik S.; Jivani, Nurudin P.

2010-01-01

Background/Aim: This study was designed to investigate the possible effect of exenatide (Glucagon like Peptide-1 receptor agonist) on liver injury (distant organ) induced by renal ischemia reperfusion (IR) in diabetic rats. Materials and Methods: In vivo renal IR was performed in both type 2 diabetic and normal rats. Each protocol comprised ischemia for 30 minutes followed by reperfusion for 24 hours and a treatment period of 14 days before induction of ischemia. Results: Lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity and nitric oxide level in liver tissue were significantly increased (P < 0.01, P < 0.001, P < 0.001, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Antioxidant enzymes like glutathione, superoxide dismutase, catalase and glutathione peroxidase were significantly reduced (P < 0.05, P < 0.05, P < 0.01, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Exenatide treatment significantly normalized (P < 0.01), these biochemical parameters in treated rats compared to diabetic IR rats. Serum creatinine phosphokinase activity and liver function enzymes were also significantly normalized (P < 0.001, P < 0.001, respectively), after administration of exenatide. Conclusion: Exenatide exerted protective effect on exaggerated remote organ (liver) injury induced by renal IR in diabetes. PMID:20616412

Isolated heart and liver transplant recipients are at low risk for polyomavirus BKV nephropathy.

PubMed

Puliyanda, Dechu P; Amet, Nurmamet; Dhawan, Archana; Hilo, Lara; Radha, Raju K; Bunnapradist, Suphamai; Czer, Lawrence; Martin, Paul; Jordan, Stanley; Toyoda, Mieko

2006-01-01

BKV infection and nephropathy is a significant cause of allograft dysfunction in kidney transplantation. BKV viremia, rather than viruria, corresponds to BKV nephropathy. The prevalence of BKV viremia in non-renal solid organ transplants has not been systematically evaluated. We determined prevalence of BKV viremia in kidney, combined kidney-heart, kidney-liver, kidney-pancreas, kidney-heart-liver, and heart and liver transplant recipients using BKV-PCR. Seven out of 173 (4%) kidney transplant recipients had BKV viremia, with BKV>2 x 10(5) copies/mL in 6/7 and 1.9 x 10(3) in the remaining one patient. BKV viremia was not found in 24 heart transplant recipients, whereas 1/37 (2.7%) liver transplants showed low copy numbers (< or =10(3)). BKV-PCR< or =10(3) copies/mL were also found in one of each combined kidney-heart and kidney-liver transplant recipients. BKV nephropathy was proven by biopsy in 4/6 patients with high BKV viral loads. All six patients showed renal dysfunction, requiring reduction in immunosuppression and antiviral therapy. All four patients with low BKV viral loads (1.9 x 10(3) or < or =10(3)) showed stable renal function after reduction of immunosuppression or no treatment, respectively. Higher BKV levels in plasma are associated with renal dysfunction. Kidney transplant recipients are at high risk compared with recipients of isolated heart or liver allografts, for development of BKV nephropathy.

Renal outcomes of simultaneous liver-kidney transplantation compared to liver transplant alone for candidates with renal dysfunction.

PubMed

Brennan, Todd V; Lunsford, Keri E; Vagefi, Parsia A; Bostrom, Alan; Ma, Michael; Feng, Sandy

2015-01-01

It is unclear whether a concomitant kidney transplant grants survival benefit to liver transplant (LT) candidates with renal dysfunction (RD). We retrospectively studied LT candidates without RD (n = 714) and LT candidates with RD who underwent either liver transplant alone (RD-LTA; n = 103) or simultaneous liver-kidney transplant (RD-SLKT; n = 68). RD was defined as renal replacement therapy (RRT) requirement or modification of diet in renal disease (MDRD)-glomerular filtration rate (GFR) <25 mL/min/1.73 m(2) . RD-LTAs had worse one-yr post-transplant survival compared to RD-SLKTs (79.6% vs. 91.2%, p = 0.05). However, RD-LTA recipients more often had hepatitis C (60.2% vs. 41.2%, p = 0.004) and more severe liver disease (MELD 37.9 ± 8.1 vs. 32.7 ± 9.1, p = 0.0001). Twenty RD-LTA recipients died in the first post-transplant year. Evaluation of the cause and timing of death relative to native renal recovery revealed that only four RD-LTA recipients might have derived survival benefit from RD-SLKT. Overall, 87% of RD-LTA patients recovered renal function within one month of transplant. One yr after RD-LTA or RD-SLKT, serum creatinine (1.5 ± 1.2 mg/dL vs. 1.4 ± 0.5 mg/dL, p = 0.63) and prevalence of stage 4 or 5 chronic kidney disease (CKD; 5.9% vs. 6.8%, p = 0.11) were comparable. Our series provides little evidence that RD-SLKT would have yielded substantial short-term survival benefit to RD-LTA recipients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Renal uptake of radioactive mercury (/sup 197/HgCl/sub 2/): method for testing the functional value of each kidney. Technique--results--and clinical application in urology and nephrology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raynaud, C.

The first three chapters consider measurement of mercury renal uptake by external counting, by quantitative scintigraphy, and by the gamma camera. Some topics discussed in the remaining 14 chapters are as follows: renal depth; phantoms; precautions regarding the liver, spleen, and intestine; stability of /sup 197/HgCl/sub 2/ solutions; use of mercury renal uptake in pediatric and adult urology; indications for mercury renal uptake in renal transplants; and appraisal of the radiological and chemical toxicity of /sup 197/HgCl/sub 2/. It was concluded that mercury renal uptake is an accurate and nontraumatizing method of measuring the functional value of each kidney. Itmore » makes it possible to determine whether a kidney is normal or pathological and to what extent its function is diminished or increased. (HLW)« less

Hepatorenal syndrome.

PubMed

Papper, S

1980-01-01

Renal failure without apparent cause (the hepatorenal syndrome) may develop in the course of cirrhosis of the liver. While the development of renal failure bears a poor prognosis, spontaneous recovery can occur. The data suggest that for the most part patients die in rather than of renal failure. The latter seems to be only part of a broader more fundamental disturbance. The pathogenesis of HRS is unknown, but the evidence supports an impairment of effective renal perfusion. The two major hypotheses concerning the nature of the impaired perfusion are that it is a physiologic response to alterations in the extrarenal circulation, and that there is an unidentified humoral agent(s) produced by or inadequately inactivated by or bypassing the diseased liver and causing circulatory changes in the kidney as well as in other organs. It is possible that both mechanisms are operative. Treatment is unsatisfactory and emphasis is presently best placed upon searching for more treatable causes of renal functional impairment in individual patients.

Extracorporeal shock wave lithotripsy (ESWL) of a renal calculus in a liver transplant recipient: report of a severe complication--a case report.

PubMed

Friedersdorff, F; Buckendahl, J; Fuller, T F; Cash, H

2010-11-01

Extracorporeal shock wave lithotripsy (ESWL) has evolved as a standard treatment modality for calculi of the upper urinary tract. Noninvasive ESWL shows rare life-threatening complications. Herein we have reported the case of a liver transplant recipient who developed severe renal hemorrhage after ESWL of a renal calculus. Transfusion of erythrocytes and platelets led to anaphylactic shock with acute renal failure requiring intensive care. The patient fully recovered shortly thereafter and was discharged home with a residual left kidney stone measuring 8 mm. A 55-year-old man with a single left kidney underwent ESWL due to symptomatic left nephrolithiasis. He had undergone successful liver transplantation 11 years earlier. At the time of ESWL his liver functions were normal and his serum creatinine level was 1.3 mg/dL. Two weeks before the treatment a double pigtail ureteral stent was inserted because of a symptomatic left hydronephrosis. Several hours after ESWL treatment the patient complained of left-sided flank pain. An ultrasound revealed a large subcapsular hematoma of the left kidney, which was confirmed using abdominal computed tomography (CT). With the patient being hemodynamically stable, we opted for conservative management. Despite postinterventional complications, the patient made a fast recovery. ESWL is a noninvasive, safe, and efficient method to treat renal calculi. Patients who are at risk for hemorrhage should undergo close postinterventional monitoring, including red blood cell count and renal ultrasound. Copyright © 2010 Elsevier Inc. All rights reserved.

The first Polish liver transplantation after Roux-en-Y gastric bypass surgery for morbid obesity: a case report and literature review.

PubMed

Marszałek, Rafał; Ziemiański, Paweł; Łągiewska, Beata; Pacholczyk, Marek; Domienik-Karłowicz, Justyna; Trzebicki, Janusz; Wierzbicki, Zbigniew; Jankowski, Krzysztof; Kosieradzki, Maciej; Wasiak, Dariusz; Jonas, Maurycy; Pruszczyk, Piotr; Durlik, Magdalena; Lisik, Wojciech; Chmura, Andrzej

2015-02-25

Morbid obesity is associated with liver pathology, most commonly non-alcoholic steatohepatitis (NASH) leading to cirrhosis. However, the morbid obesity impedes qualification for organ transplantation. We present a case report of a 56-year-old woman who underwent bariatric procedure followed by liver transplantation (LTx). Her initial weight was 130.2 kg (BMI 50.9 kg/m2). The patient had a history of arterial hypertension, diabetes, gonarthrosis, and obstructive sleep apnea syndrome and no history of alcohol abuse. She underwent Roux-en-Y gastric bypass (RYGB) procedure. The routine intraoperative liver biopsy revealed fibrosis (III°), steatosis (II°), and intra-acinar inflammation. The operation led to a substantial loss of weight. Two years after the surgery the patient was referred to the Transplantation Clinic of Department of General Surgery and Transplantology with suspicion of liver failure due to advanced cirrhosis, which could be a result of previously diagnosed NASH and, probably, excessive alcohol use after bariatric surgery. The patient was qualified for elective LTx, which was performed 3 years after the RYGB. Immediately before LTx, the patient's weight was 65 kg (BMI 25.4 kg/m²). The postoperative period was complicated by bleeding into the peritoneal cavity, which required reoperation. She also had renal failure, requiring renal replacement therapy. One year after LTx, she showed stable liver function with normal transaminases activity and bilirubin concentration, remission of diabetes, and good renal function. Steatohepatitis in morbidly obese patients may lead to cirrhosis. Bariatric procedure can be a bridge to liver transplantation for morbidly obese patients with advanced liver fibrosis.

Primary Hyperoxaluria

PubMed Central

Harambat, Jérôme; Fargue, Sonia; Bacchetta, Justine; Acquaviva, Cécile; Cochat, Pierre

2011-01-01

Primary hyperoxalurias (PH) are inborn errors in the metabolism of glyoxylate and oxalate. PH type 1, the most common form, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine, glyoxylate aminotransferase (AGT) resulting in overproduction and excessive urinary excretion of oxalate. Recurrent urolithiasis and nephrocalcinosis are the hallmarks of the disease. As glomerular filtration rate decreases due to progressive renal damage, oxalate accumulates leading to systemic oxalosis. Diagnosis is often delayed and is based on clinical and sonographic findings, urinary oxalate assessment, DNA analysis, and, if necessary, direct AGT activity measurement in liver biopsy tissue. Early initiation of conservative treatment, including high fluid intake, inhibitors of calcium oxalate crystallization, and pyridoxine in responsive cases, can help to maintain renal function in compliant subjects. In end-stage renal disease patients, the best outcomes have been achieved with combined liver-kidney transplantation which corrects the enzyme defect. PMID:21748001

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis

PubMed Central

Facciorusso, Antonio; Amoruso, Annabianca; Neve, Viviana; Antonino, Matteo; Prete, Valentina Del; Barone, Michele

2014-01-01

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2 (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients. PMID:25429317

Renal effects of the novel selective adenosine A1 receptor blocker SLV329 in experimental liver cirrhosis in rats.

PubMed

Hocher, Berthold; Heiden, Susi; von Websky, Karoline; Arafat, Ayman M; Rahnenführer, Jan; Alter, Markus; Kalk, Philipp; Ziegler, Dieter; Fischer, Yvan; Pfab, Thiemo

2011-03-10

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A(1) receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A(1) receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (-36.5%, p<0.05), especially in those receiving furosemide (-41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A(1) receptor antagonists are clinically beneficial at different stages of liver cirrhosis.

Complications of cirrhosis. A 50 years flashback.

PubMed

Møller, Søren; Bendtsen, Flemming

2015-06-01

In patients with cirrhosis and portal hypertension, it is largely the frequency and severity of complications relating to the diseased liver, degree of portal hypertension and hemodynamic derangement that determine the prognosis. It can be considered as a multiple organ failure that apart from the liver involves the heart, lungs, kidneys, the immune systems and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. With the progression of the disease development of portal hypertension leads to formation of esophageal varices and ascites. The circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitating the hepatorenal syndrome. Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation.

CAN ULTRASOUND ABDOMEN HELP IN EARLY DIAGNOSIS OF DIABETES MELLITUS? AN OBSERVATIONAL STUDY.

PubMed

Anwar, Javed; Aamir, Muhammad Omer; Sanaullah; Imdad, Zeeshan ul Hasnain; Parveen, Ishrat; Yousaf, Nasreen

2015-01-01

Diabetes mellitus is a common disease. Similarly, ultrasound findings of fatty change and renal crystals are commonly seen on ultrasound. In the personal observation of the main author over the past so many years it was noticed that Diabetes Mellitus, Fatty liver and renal crystals all sit well together. This study tries to establish a relationship between diabetes mellitus renal echogenic foci and fatty liver. This study is first of its kind, as nobody has ever before investigated an association between the renal echogenic foci and fatty liver in relation to diabetes mellitus. This cross-sectional, observational study was conducted at Radiology Department Combined Military Hospital, Kohat From 2nd June 2013 to 30th May 2014. Three hundred patients were collected on the basis of having fatty liver and renal echogenic foci on ultrasound and three hundred more patients were collected who had no fatty liver or renal echogenic foci on ultrasound. Their labs were done for diabetes mellitus. The patients having renal echogenic foci together with fatty liver had 83% positive rate of being diabetics, while patients with no fatty liver and no echogenic foci on ultrasonography had only 0.6% Positive rate of being diabetics. Our results provided the first demonstration of an association between renal echogenic foci together with fatty liver with the diabetes mellitus. Thus ultrasound examination of abdomen can be helpful in its early diagnosis if we make a protocol of doing fasting and random blood sugars in all those patients who have positive renal echogenic foci and fatty liver on their ultrasound examination.

Early outcomes of liver transplants in patients receiving organs from hypernatremic donors.

PubMed

Khosravi, Mohammad Bagher; Firoozifar, Mohammad; Ghaffaripour, Sina; Sahmeddini, Mohammad Ali; Eghbal, Mohammad Hossien

2013-12-01

Uncorrected hypernatremia in organ donors has been associated with poor graft or patient survival during liver transplants. However, recent studies have found no association between the donor serum sodium and transplant outcome. This study sought to show the negative effect donor hypernatremia has on initial liver allograft function. This is the first study to investigate international normalized ratio and renal factors of patients with normal and those with hypernatremic donor livers. This study was conducted at the Shiraz Transplant Research Center in Shiraz, Iran, between May 2009, and July 2011. Four hundred seven consecutive adult orthotopic liver transplants were performed at the University of Shiraz Medical Center. There were 93 donors in the group with hypernatremia with terminal serum sodium of 155 mEq/L or greater (group 1), and 314 with terminal serum sodium less than 155 mEq/L (group 2). Posttransplant data after 5 days showed that aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and kidney function did not differ between the groups. Hypernatremia is the most important complication after brain death. Previous studies have suggested donor hypernatremia results in a greater incidence of early postoperative graft dysfunction in liver transplant and is considered one of the extended criteria donor. However, in recent years, this hypothesis has been questioned. Our study shows no difference between patients' initial results of liver and kidney functioning with normal and hypernatremic donor livers. This is the first study to investigate international normalized ratio as a fundamental factor in defining early allograft dysfunction and renal factors between patients with normal and hypernatremic donor's livers.

Incidence and Patient Outcomes in Renal Replacement Therapy After Orthotopic Liver Transplant.

PubMed

Ayhan, Asude; Ersoy, Zeynep; Ulas, Aydin; Zeyneloglu, Pinar; Pirat, Arash; Haberal, Mehmet

2017-02-01

Our objective was to evaluate the incidence of renal replacement therapy after orthotopic liver transplant and to evaluate and analyze patient outcomes. We performed a retrospective analysis of 177 consecutive patients at a tertiary care unit who underwent orthotopic liver transplant between January 2010 and June 2016. Patients who were admitted to the intensive care unit after orthotopic liver transplant and who required renal replacement therapy were included. A total of 177 (79 adult, 98 pediatric) orthotopic liver transplants were performed during the study period. Of these, 35 patients (19%) required renal replacement therapy during the early posttransplantation period. After excluding 5 patients with previous chronic renal failure, 30 patients (17%; 20 adult [25% ], 10 pediatric [10% ]) with acute kidney injury required renal replacement therapy. The mean patient age was 31.1 ± 20.0 years, with a mean Model for End-stage Liver Disease score of 16.7 ± 12.3. Of the patients with acute kidney injury who underwent renal replacement therapy, in-hospital mortality was 23.3% (7 of 30 patients), and 40% remained on dialysis. No significant difference was seen in mortality between early versus delayed initiation of renal replacement therapy in patients with stage 3 acute kidney injury (P = .17). Of liver transplant recipients who present with acute kidney injury, 19% require renal replacement therapy, and in-hospital mortality is 20% in the early postoperative period.

Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis

PubMed Central

Gedaly, Roberto; Jeon, Hoonbae; Johnston, Thomas D; McHugh, Patrick P; Rowland, Randall G; Ranjan, Dinesh

2008-01-01

Background Carcinoid tumors are characteristically low grade malignant neoplasms with neuroendocrine differentiation that arise in various body sites, most commonly the lung and gastrointestinal tract, but less frequently the kidneys, breasts, ovaries, testes, prostate and other locations. We report a case of a carcinoid of renal origin with synchronous single liver metastases on radiological studies. Case presentation A 45 year-old patient who presented with abdominal pain was found on CT scan to have lesions in the right ovary, right kidney, and left hepatic lobe. CA-125, CEA, and CA 19-9 were within normal limits, as were preoperative liver function tests and renal function. Biopsy of the liver mass demonstrated metastatic neuroendocrine tumor. At laparotomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, radical right nephrectomy with lymphadenectomy, and left hepatectomy. Pathology evaluation reported a right ovarian borderline serous tumor, well-differentiated neuroendocrine carcinoma of the kidney (carcinoid) with 2 positive retroperitoneal lymph nodes, and a single liver metastasis. Immunohistochemistry revealed that this lesion was positive for synaptophysin and CD56, but negative for chromogranin as well as CD10, CD7, and CD20, consistent with a well-differentiated neuroendocrine tumor. She is doing well one year after her initial surgery, with no evidence of tumor recurrence. Conclusion Early surgical intervention, together with careful surveillance and follow-up, can achieve successful long-term outcomes in patients with this rare malignancy. PMID:18430248

Acute Kidney Injury in Patients with Cirrhosis

PubMed Central

Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.

2015-01-01

Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266

MRI to assess renal structure and function.

PubMed

Artunc, Ferruh; Rossi, Cristina; Boss, Andreas

2011-11-01

In addition to excellent anatomical depiction, MRI techniques have expanded to study functional aspects of renal physiology, such as renal perfusion, glomerular filtration rate (GFR) or tissue oxygenation. This review will focus on current developments with an emphasis on clinical applicability. The method of GFR determination is largely heterogeneous and still has weaknesses. However, the technique of employing liver disappearance curves has been shown to be accurate in healthy persons and patients with chronic kidney disease. In potential kidney donors, complete evaluation of kidney anatomy and function can be accomplished in a single-stop investigation. Techniques without contrast media can be utilized to measure renal tissue oxygenation (blood oxygen level-dependent MRI) or perfusion (arterial spin labeling) and could aid in the diagnosis and treatment of ischemic renal diseases, such as renal artery stenosis. Diffusion imaging techniques may provide information on spatially restricted water diffusion and tumor cellularity. Functional MRI opens new horizons in studying renal physiology and pathophysiology in vivo. Although extensively utilized in research, labor-intensive postprocessing and lack of standardization currently limit the clinical applicability of functional MRI. Further studies are necessary to evaluate the clinical value of functional magnetic resonance techniques for early discovery and characterization of kidney disease.

[Acetaminophen (paracetamol) causing renal failure: report on 3 pediatric cases].

PubMed

Le Vaillant, J; Pellerin, L; Brouard, J; Eckart, P

2013-06-01

Renal failure secondary to acetaminophen poisoning is rare and occurs in approximately 1-2 % of patients with acetaminophen overdose. The pathophysiology is still being debated, and renal acetaminophen toxicity consists of acute tubular necrosis, without complication if treated promptly. Renal involvement can sometimes occur without prior liver disease, and early renal manifestations usually occur between the 2nd and 7th day after the acute acetaminophen poisoning. While therapy is exclusively symptomatic, sometimes serious metabolic complications can be observed. The monitoring of renal function should therefore be considered as an integral part of the management of children with acute, severe acetaminophen intoxication. We report 3 cases of adolescents who presented with acute renal failure as a result of voluntary drug intoxication with acetaminophen. One of these 3 girls developed severe renal injury without elevated hepatic transaminases. None of the 3 girls' renal function required hemodialysis, but one of the 3 patients had metabolic complications after her acetaminophen poisoning. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Fluid and electrolyte disturbances in cirrhosis.

PubMed

Papper, S

1976-01-01

Glomerular filtration rate and renal plasma flow may be normal, reduced or increased in cirrhosis. The mechanism of departures from normal is not known. Other renal functional changes in cirrhosis include avid sodium reabsorption, impaired concentrating and diluting abilities, and partial renal tubular acidosis. Fluid and electrolyte disorders are common. Sodium retention with edema and ascites should generally be treated conservatively because they tend to disappear as the liver heals and because forced diuresis has hazards. The indications for diuretics are (1) incipient or overt atelectasis; (2) abdominal distress; and (3) possibility of skin breakdown. Hyponatremia is common and its mechanism and treatment must be assessed in each patient. Hypokalemia occurs and requires treatment. Respiratory alkalosis and renal tubular acidosis seldom need therapy. The hepatorenal syndrome is defined as functional renal failure in the absence of other known causes of renal functional impairment. The prognosis is terrible and therapy is unsatisfactory. The best approach is not to equate the occurrence of renal failure in cirrhosis with the hepatorenal syndrome. Rather the physician should first explore all treatable causes of renal failure, eg, dehydration, obstruction, infection, heart failure, potassium depletion, and others.

Pretransplantation Cystatin C, but not Creatinine, Predicts 30-day Cardiovascular Events and Mortality in Liver Transplant Recipients With Normal Serum Creatinine Levels.

PubMed

Kwon, H-M; Moon, Y-J; Jung, K-W; Jun, I-G; Song, J-G; Hwang, G-S

2018-05-01

The connection between renal dysfunction and cardiovascular dysfunction has been consistently shown. In patients with liver cirrhosis, renal dysfunction shows a tight correlation with prognosis after liver transplantation (LT); therefore, precise renal assessment is mandatory. Cystatin C, a sensitive biomarker for assessing renal function, has shown superiority in detecting mild renal dysfunction compared to classical biomarker creatinine. In this study, we aimed to compare cystatin C and creatinine in predicting 30-day major cardiovascular events (MACE) and all-cause mortality in LT recipients with normal serum creatinine levels. Between May 2010 and October 2015, 1181 LT recipients (mean Model for End-stage Liver Disease score 12.1) with pretransplantation creatinine level ≤1.4 mg/dL were divided into tertiles according to each renal biomarker. The 30-day MACE was a composite of troponin I >0.2 ng/mL, arrhythmia, congestive heart failure, death, and cerebrovascular events. The highest tertile of cystatin C (≥0.95 mg/L) was associated with a higher risk for a 30-day MACE event (odds ratio: 1.62; 95% confidence interval: 1.07 to 2.48) and higher risk of death (hazard ratio: 1.96; 95% confidence interval: 1.04 to 3.67) than the lowest tertile (<0.74 mg/L) after multivariate adjustments. However, the highest tertile of creatinine level showed neither increasing MACE event rate nor worse survival rate compared with the lowest tertile (both insignificant after multivariate adjustment). Pretransplantation cystatin C is superior in risk prediction of MACE and all-cause mortality in LT recipients with normal creatinine, compared to creatinine. It would assist further risk stratification which may not be detected with creatinine. Copyright © 2018 Elsevier Inc. All rights reserved.

Venovenous Bypass Is Associated With a Lower Incidence of Acute Kidney Injury After Liver Transplantation in Patients With Compromised Pretransplant Renal Function.

PubMed

Sun, Kai; Hong, Fu; Wang, Yun; Agopian, Vatche G; Yan, Min; Busuttil, Ronald W; Steadman, Randolph H; Xia, Victor W

2017-11-01

Although the hemodynamic benefits of venovenous bypass (VVB) during liver transplantation (LT) are well appreciated, the impact of VVB on posttransplant renal function is uncertain. The aim of this study was to determine if VVB was associated with a lower incidence of posttransplant acute kidney injury (AKI). Medical records of adult (≥18 years) patients who underwent primary LT between 2004 and 2014 at a tertiary hospital were reviewed. Patients who required pretransplant renal replacement therapy and intraoperative piggyback technique were excluded. Patients were divided into 2 groups, VVB and non-VVB. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups. Propensity match was used to control selection bias that occurred before VVB and multivariable logistic regression was used to control confounding factors during and after VVB. Of 1037 adult patients who met the study inclusion criteria, 247 (23.8%) received VVB. A total of 442 patients (221 patients in each group) were matched. Aftermatch patients were further divided according to a predicted probability AKI model using preoperative creatinine (Cr), VVB, and intraoperative variables into 2 subgroups: normal and compromised pretransplant renal functions. In patients with compromised pretransplant renal function (Cr ≥1.2 mg/dL), the incidence of AKI was significantly lower in the VVB group compared with the non-VVB group (37.2% vs 50.8%; P = .033). VVB was an independent risk factor negatively associated with AKI (odds ratio, 0.1; 95% confidence interval, 0.1-0.4; P = .001). Renal replacement in 30 days and 1-year recipient mortality were not significantly different between the 2 groups. The incidence of posttransplant AKI was not significantly different between the 2 groups in patients with normal pretransplant renal function (Cr <1.2 mg/dL). In this large retrospective study, we demonstrated that utilization of intraoperative VVB was associated with a significantly lower incidence of posttransplant AKI in patients with compromised pretransplant renal function. Further studies to assess the role of intraoperative VVB in posttransplant AKI are warranted.

Fast simultaneous assessment of renal and liver function using polymethine dyes in animal models of chronic and acute organ injury.

PubMed

Press, A T; Butans, M J; Haider, T P; Weber, C; Neugebauer, S; Kiehntopf, M; Schubert, U S; Clemens, M G; Bauer, M; Kortgen, A

2017-11-13

Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.

Albumin in chronic liver disease: structure, functions and therapeutic implications.

PubMed

Spinella, Rosaria; Sawhney, Rohit; Jalan, Rajiv

2016-01-01

Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.

Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity of Liver Damage at the Time of Transplantation

PubMed Central

Habib, Shahid; Khan, Khalid; Hsu, Chiu-Hsieh; Meister, Edward; Rana, Abbas; Boyer, Thomas

2017-01-01

Background We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. Methods Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) ≤ 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. Results Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. Conclusions SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated. PMID:28496531

Multiphoton imaging for assessing renal disposition in acute kidney injury

NASA Astrophysics Data System (ADS)

Liu, Xin; Liang, Xiaowen; Wang, Haolu; Roberts, Darren M.; Roberts, Michael S.

2016-11-01

Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients.

PubMed

Chen, W-Y; Lee, C-Y; Lin, P-Y; Hsieh, C-E; Ko, C-J; Lin, K-H; Lin, C-C; Ming, Y-Z; Chen, Y-L

2017-03-01

Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients. In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach. Dose-adjusted blood trough levels of tacrolimus tended to be significantly (P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval [CI] = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups. Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

PubMed

Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

2011-01-01

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

Radon inhalation protects mice from carbon-tetrachloride-induced hepatic and renal damage.

PubMed

Kataoka, Takahiro; Nishiyama, Yuichi; Toyota, Teruaki; Yoshimoto, Masaaki; Sakoda, Akihiro; Ishimori, Yuu; Aoyama, Yutaka; Taguchi, Takehito; Yamaoka, Kiyonori

2011-12-01

We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl4)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 18 kBq/m3 radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl4 was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl4 injection, suggesting that radon inhalation alleviates CCl4-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl(4)-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl4-induced hepatic and renal damage in mice.

Simultaneous Liver-Kidney Allocation Policy: A Proposal to Optimize Appropriate Utilization of Scarce Resources.

PubMed

Formica, R N; Aeder, M; Boyle, G; Kucheryavaya, A; Stewart, D; Hirose, R; Mulligan, D

2016-03-01

The introduction of the Mayo End-Stage Liver Disease score into the Organ Procurement and Transplantation Network (OPTN) deceased donor liver allocation policy in 2002 has led to a significant increase in the number of simultaneous liver-kidney transplants in the United States. Despite multiple attempts, clinical science has not been able to reliably predict which liver candidates with renal insufficiency will recover renal function or need a concurrent kidney transplant. The problem facing the transplant community is that currently there are almost no medical criteria for candidacy for simultaneous liver-kidney allocation in the United States, and this lack of standardized rules and medical eligibility criteria for kidney allocation with a liver is counter to OPTN's Final Rule. Moreover, almost 50% of simultaneous liver-kidney organs come from a donor with a kidney donor profile index of ≤0.35. The kidneys from these donors could otherwise be allocated to pediatric recipients, young adults or prior organ donors. This paper presents the new OPTN and United Network of Organ Sharing simultaneous liver-kidney allocation policy, provides the supporting evidence and explains the rationale on which the policy was based. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Germanium in ginseng is low and causes no sodium and water retention or renal toxicity in the diuretic-resistant rats

PubMed Central

Tan, Chunjiang; Xiao, Lu; Chen, Wenlie

2015-01-01

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes. PMID:25711879

Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression.

PubMed

Costa, Elísio; Fernandes, João; Ribeiro, Sandra; Sereno, José; Garrido, Patrícia; Rocha-Pereira, Petronila; Coimbra, Susana; Catarino, Cristina; Belo, Luís; Bronze-da-Rocha, Elsa; Vala, Helena; Alves, Rui; Reis, Flávio; Santos-Silva, Alice

2014-12-01

Our aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, iron metabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher urea, creatinine, interferon (INF)-gamma, ferritin and soluble transferrin receptor serum levels, as well as increased counts of reticulocytes and RDW. In addition, these rats showed significant lower erythropoietin (EPO) and iron serum levels. Concerning gene expression of iron regulatory proteins, old rats presented significantly higher mRNA levels of hepcidin (Hamp), transferrin (TF), transferrin receptor 2 (TfR2) and hemojuvelin (HJV); divalent metal transporter 1 (DMT1) mRNA levels were significantly higher in duodenal tissue; EPO gene expression was significantly higher in liver and lower in kidney, and the expression of the EPOR was significantly higher in both liver and kidney. Our results showed that aging is associated with impaired renal function, which could be in turn related with the inflammatory process and with a decline in EPO renal production. Moreover, we also propose that aging may be associated with INF-gamma-induced inflammation and with alterations upon iron regulatory proteins gene expression.

Impact of liver volume and liver function on posthepatectomy liver failure after portal vein embolization- A multivariable cohort analysis.

PubMed

Alizai, Patrick H; Haelsig, Annabel; Bruners, Philipp; Ulmer, Florian; Klink, Christian D; Dejong, Cornelis H C; Neumann, Ulf P; Schmeding, Maximilian

2018-01-01

Liver failure remains a life-threatening complication after liver resection, and is difficult to predict preoperatively. This retrospective cohort study evaluated different preoperative factors in regard to their impact on posthepatectomy liver failure (PHLF) after extended liver resection and previous portal vein embolization (PVE). Patient characteristics, liver function and liver volumes of patients undergoing PVE and subsequent liver resection were analyzed. Liver function was determined by the LiMAx test (enzymatic capacity of cytochrome P450 1A2). Factors associated with the primary end point PHLF (according to ISGLS definition) were identified through multivariable analysis. Secondary end points were 30-day mortality and morbidity. 95 patients received PVE, of which 64 patients underwent major liver resection. PHLF occurred in 7 patients (11%). Calculated postoperative liver function was significantly lower in patients with PHLF than in patients without PHLF (67 vs. 109 μg/kg/h; p = 0.01). Other factors associated with PHLF by univariable analysis were age, future liver remnant, MELD score, ASA score, renal insufficiency and heart insufficiency. By multivariable analysis, future liver remnant was the only factor significantly associated with PHLF (p = 0.03). Mortality and morbidity rates were 4.7% and 29.7% respectively. Future liver remnant is the only preoperative factor with a significant impact on PHLF. Assessment of preoperative liver function may additionally help identify patients at risk for PHLF.

Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang Cheng; Behr, Melissa; Xie Fang

2008-02-15

Chloroform causes hepatic and renal toxicity in a number of species. In vitro studies have indicated that chloroform can be metabolized by P450 enzymes in the kidney to nephrotoxic intermediate, although direct in vivo evidence for the role of renal P450 in the nephrotoxicity has not been reported. This study was to determine whether chloroform renal toxicity persists in a mouse model with a liver-specific deletion of the P450 reductase (Cpr) gene (liver-Cpr-null). Chloroform-induced renal toxicity and chloroform tissue levels were compared between the liver-Cpr-null and wild-type mice at 24 h following differing doses of chloroform. At a chloroform dosemore » of 150 mg/kg, the levels of blood urea nitrogen (BUN) were five times higher in the exposed group than in the vehicle-treated one for the liver-Cpr-null mice, but they were only slightly higher in the exposed group than in the vehicle-treated group for the wild-type mice. Severe lesions were found in the kidney of the liver-Cpr-null mice, while only mild lesions were found in the wild-type mice. At a chloroform dose of 300 mg/kg, severe kidney lesions were observed in both strains, yet the BUN levels were still higher in the liver-Cpr-null than in the wild-type mice. Higher chloroform levels were found in the tissues of the liver-Cpr-null mice. These findings indicated that loss of hepatic P450-dependent chloroform metabolism does not protect against chloroform-induced renal toxicity, suggesting that renal P450 enzymes play an essential role in chloroform renal toxicity.« less

Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α.

PubMed

Adil, Mohammad; Kandhare, Amit D; Visnagri, Asjad; Bodhankar, Subhash L

2015-01-01

Chronic exposure of a naturally occurring metal arsenic leads to renal and hepatic diseases. Naringin, a flavanone glycoside, possesses anti-inflammatory and anti-oxidant potential. The aim of this investigation was to evaluate the protective effect of naringin against arsenic-induced renal and hepatic toxicity in rats. Renal and hepatic toxicity was induced in rats by sodium arsenite (5 mg/kg, p.o.). Rats were treated orally with either vehicle or naringin (20, 40, and 80 mg/kg) or Coenzyme Q10 (10 mg/kg) for 28 days. Various biochemical, histological, and molecular biomarkers were assessed in kidney and liver. Treatment with naringin (40 and 80 mg/kg) significantly and dose-dependently restored (p < 0.01 and p < 0.001) altered levels of kidney (serum creatinine, urine creatinine, BUN, uric acid, and creatinine clearance) and liver function test (AST and ALT) induced by sodium arsenite. Elevated levels of oxido-nitrosative stress in renal and hepatic tissue was significantly and dose-dependently decreased (p < 0.01 and p < 0.001) by naringin (40 and 80 mg/kg) treatment. It significantly and dose-dependently down-regulated (p < 0.01 and p < 0.001) renal KIM-1, Caspase-3, TGF-β, and TNF-α mRNA expression. Histopathological alteration induced in kidney and liver by sodium arsenite was reduced by naringin (40 and 80 mg/kg) treatment. In conclusion, naringin treatment ameliorates arsenic-induced renal and hepatic damage in rats due its antioxidant and anti-inflammatory properties via down-regulation of elevated oxido-nitrosative stress, KIM-1, Caspase-3, TGF-β, and TNF-α levels.

The Sodium-Glucose Cotransporter 2 Inhibitor Dapagliflozin Prevents Renal and Liver Disease in Western Diet Induced Obesity Mice

PubMed Central

Wang, Dong; Luo, Yuhuan; Wang, Xiaoxin; Orlicky, David J.; Myakala, Komuraiah; Yang, Pengyuan; Levi, Moshe

2018-01-01

Obesity and obesity related kidney and liver disease have become more prevalent over the past few decades, especially in the western world. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with promising effects on cardiovascular and renal function. Given SGLT2 inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of the highly selective renal SGLT2 inhibitor dapagliflozin in mice with Western diet (WD) induced obesity. Low fat (LF) diet or WD-fed male C57BL/6J mice were treated with dapagliflozin for 26 weeks. Dapagliflozin attenuated the WD-mediated increases in body weight, plasma glucose and plasma triglycerides. Treatment with dapagliflozin prevented podocyte injury, glomerular pathology and renal fibrosis determined by second harmonic generation (SHG), nephrin, synaptopodin, collagen IV, and fibronectin immunofluorescence microscopy. Oil Red O staining showed dapagliflozin also decreased renal lipid accumulation associated with decreased SREBP-1c mRNA abundance. Moreover, renal inflammation and oxidative stress were lower in the dapagliflozin-treated WD-fed mice than in the untreated WD-fed mice. In addition, dapagliflozin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic lipid accumulation as determined by H&E and Oil Red O staining, and Coherent Anti-Stokes Raman Scattering (CARS) microscopy, and hepatic fibrosis as determined by picrosirius red (PSR) staining and TPE-SHG microscopy in WD-fed mice. Thus, our study demonstrated that the co-administration of the SGLT2 inhibitor dapagliflozin attenuates renal and liver disease during WD feeding of mice. PMID:29301371

The Sodium-Glucose Cotransporter 2 Inhibitor Dapagliflozin Prevents Renal and Liver Disease in Western Diet Induced Obesity Mice.

PubMed

Wang, Dong; Luo, Yuhuan; Wang, Xiaoxin; Orlicky, David J; Myakala, Komuraiah; Yang, Pengyuan; Levi, Moshe

2018-01-03

Obesity and obesity related kidney and liver disease have become more prevalent over the past few decades, especially in the western world. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with promising effects on cardiovascular and renal function. Given SGLT2 inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of the highly selective renal SGLT2 inhibitor dapagliflozin in mice with Western diet (WD) induced obesity. Low fat (LF) diet or WD-fed male C57BL/6J mice were treated with dapagliflozin for 26 weeks. Dapagliflozin attenuated the WD-mediated increases in body weight, plasma glucose and plasma triglycerides. Treatment with dapagliflozin prevented podocyte injury, glomerular pathology and renal fibrosis determined by second harmonic generation (SHG), nephrin, synaptopodin, collagen IV, and fibronectin immunofluorescence microscopy. Oil Red O staining showed dapagliflozin also decreased renal lipid accumulation associated with decreased SREBP-1c mRNA abundance. Moreover, renal inflammation and oxidative stress were lower in the dapagliflozin-treated WD-fed mice than in the untreated WD-fed mice. In addition, dapagliflozin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic lipid accumulation as determined by H&E and Oil Red O staining, and Coherent Anti-Stokes Raman Scattering (CARS) microscopy, and hepatic fibrosis as determined by picrosirius red (PSR) staining and TPE-SHG microscopy in WD-fed mice. Thus, our study demonstrated that the co-administration of the SGLT2 inhibitor dapagliflozin attenuates renal and liver disease during WD feeding of mice.

Hair and bone as predictors of tissular mercury concentration in the western Alaska red fox, Vulpes vulpes.

PubMed

Dainowski, B H; Duffy, L K; McIntyre, J; Jones, P

2015-06-15

We evaluated if total mercury (THg) concentrations of keratin-based and bone-based tissues can predict THg concentrations in skeletal muscle, renal medulla, renal cortex, and liver. The THg concentration in matched tissues of 65 red foxes, Vulpes vulpes, from western Alaska was determined. Hair THg concentration had a significant positive correlation with liver, renal medulla, renal cortex, and muscle. The THg concentration for males and females is moderately predictive of THg concentration in the renal cortex and liver for these foxes based on R(2) values (R(2)=0.61 and 0.63, respectively). Bone is weakly predictive of THg concentration in muscle (R(2)=0.40), but not a reliable tissue to predict THg concentration in liver (R(2)=0.24), renal cortex (R(2)=0.35), or renal medulla (R(2)=0.25). These results confirm the potential use of trapped animals, specifically foxes, as useful Arctic sentinel species to inform researchers about patterns in THg levels over time as industrialization of the Arctic continues. Copyright © 2015 Elsevier B.V. All rights reserved.

Liver function testing with nuclear medicine techniques is coming of age.

PubMed

Bennink, Roelof J; Tulchinsky, Mark; de Graaf, Wilmar; Kadry, Zakiyah; van Gulik, Thomas M

2012-03-01

Liver function is a broad term, as the organ participates in a multitude of different physiological and biochemical processes, including metabolic, synthetic, and detoxifying functions. However, it is the function of the hepatocyte that is central to sustaining normal life and dealing with disease states. When the liver begins to fail in severely ill patients, it forecasts a terminal outcome. However, unlike the glomerular filtration rate which clearly quantifies the key renal function, at most practice sites, there is no clinically available quantitative test for liver function. Although it is commonplace to assess indirect evidence of that function (by measuring blood levels of its end products and by-products) and to detect an acute injury (by following rising transaminases), a widely available test that would directly measure hepatocellular function is lacking. This article reviews current knowledge on liver function studies and focuses on those nuclear medicine tests available to study the whole liver and regional liver function. The clinical application driving these tests, prediction of remnant liver function after partial hepatectomy for primary liver malignancy or metastatic disease, is addressed here in detail. The test was recently validated for this specific application and was shown to be better than the current standard of practice (computed tomography volumetry), particularly in patients with hepatic comorbidities like cirrhosis, steatosis, or cholestasis. Furthermore, early assessment of regional liver function increase after preoperative portal vein embolization becomes possible with this technology. The limiting factor to a wider acceptance of this test is based on the lack of clinical software that would allow calculation of liver function parameters. This article provides information that enables a clinical nuclear medicine facility to provide this test using readily available equipment. Furthermore, it addresses emerging clinical applications that are under investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

What are the implications of the spontaneous spleno-renal shunts in liver cirrhosis?

PubMed Central

2009-01-01

Background Although significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts presence at doppler ultrasound and the liver cirrhosis complications. Methods Design: eighty one patients out of 129 formed the study population (35 females). Chronic liver damage in these patients was caused by HCV (66), HBV (2), alcohol abuse (2) or unknown etiology, likely non-alcoholic steatohepatitis (11). Setting: two Liver Units of university/primary hospitals in Southern Italy. Main outcome measures: grading of esofageal varices; detection of ascites: assessment of hepatic encephalopathy; evaluation of liver cirrhosis severity; tracking hepatocellular carcinoma; doppler features of spleno-renal shunts and splenic flow velocity; spleen longitudinal diameter at sonography. Results The prevalence of spleno-renal shunts was 18.5%, without no difference concerning the etiology (HCV versus non-HCV, p = 0.870); the prevalence of hepatocellular carcinoma in patients with spleno-renal shunts was superior to that of patients without them (Pearson Chi-square, p = 0.006, power of sample size 74%), also after adjustment for liver decompensation (p = 0.024). The median score of hepatic encephalopathy in patients with and without spleno-renal shunts was similar, i.e., 0 (range, 0-2) versus 0 (0 - 3), p = 0.67. The median splenic vein flow velocity in patients with spleno-renal shunts was significantly inferior to that of patients without them, i.e., 13 cm/sec (95% confidence intervals, 6-18) versus 21 cm/sec (17-24), p < 0.0001. By far the largest percentage of large esophageal varices was in patients without spleno-renal shunts (p = 0.005). In contrast, the frequency of ascites and hepatic encephalopathy severity was overlapping in the two groups. BMI values but not Child-Pugh's classification predicted spleno-renal shunts (Ors = 1.84, 95% confidence intervals = 1.28-2.64, p = 0.001 and 1.145, 95% confidence intervals = 0.77-1.51, p = 0.66). Conclusion Taking into consideration the relatively small sample size, patients with spleno-renal shunts are burdened by an increased incidence of hepatocellular carcinoma. BMI predicted the spleno-renal shunts presence. PMID:19930687

Factors associated with the frequency of monitoring of liver enzymes, renal function and lipid laboratory markers among individuals initiating combination antiretroviral therapy: a cohort study.

PubMed

Gillis, Jennifer; Bayoumi, Ahmed M; Burchell, Ann N; Cooper, Curtis; Klein, Marina B; Loutfy, Mona; Machouf, Nima; Montaner, Julio Sg; Tsoukas, Chris; Hogg, Robert S; Raboud, Janet

2015-10-26

As the average age of the HIV-positive population increases, there is increasing need to monitor patients for the development of comorbidities as well as for drug toxicities. We examined factors associated with the frequency of measurement of liver enzymes, renal function tests, and lipid levels among participants of the Canadian Observational Cohort (CANOC) collaboration which follows people who initiated HIV antiretroviral therapy in 2000 or later. We used zero-inflated negative binomial regression models to examine the associations of demographic and clinical characteristics with the rates of measurement during follow-up. Generalized estimating equations with a logit link were used to examine factors associated with gaps of 12 months or more between measurements. Electronic laboratory data were available for 3940 of 7718 CANOC participants. The median duration of electronic follow-up was 3.5 years. The median (interquartile) rates of tests per year were 2.76 (1.60, 3.73), 2.55 (1.44, 3.38) and 1.42 (0.50, 2.52) for liver, renal and lipid parameters, respectively. In multivariable zero-inflated negative binomial regression models, individuals infected through injection drug use (IDU) were significantly less likely to have any measurements. Among participants with at least one measurement, rates of measurement of liver, renal and lipid tests were significantly lower for younger individuals and Aboriginal Peoples. Hepatitis C co-infected individuals with a history of IDU had lower rates of measurement and were at greater risk of having 12 month gaps between measurements. Hepatitis C co-infected participants infected through IDU were at increased risk of gaps in testing, despite publicly funded health care and increased risk of comorbid conditions. This should be taken into consideration in analyses examining factors associated with outcomes based on laboratory parameters.

A case of severe osteomalacia caused by Tubulointerstitial nephritis with Fanconi syndrome in asymptomotic primary biliary cirrhosis.

PubMed

Yamaguchi, Shintaro; Maruyama, Tatsuya; Wakino, Shu; Tokuyama, Hirobumi; Hashiguchi, Akinori; Tada, Shinichiro; Homma, Koichiro; Monkawa, Toshiaki; Thomas, James; Miyashita, Kazutoshi; Kurihara, Isao; Yoshida, Tadashi; Konishi, Konosuke; Hayashi, Koichi; Hayashi, Matsuhiko; Itoh, Hiroshi

2015-11-11

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease, characterized by increased concentrations of serum IgM and the presence of circulating anti-mitochondrial antibodies. Although bone diseases such as osteoporosis or osteodystrophy are commonly associated with PBC, osteomalacia which is caused by abnormal vitamin D metabolism, mineralization defects, and phosphate deficiency has not been recognized as a complication of PBC. We report the case of a 49-year-old Japanese woman who complained of multiple fractures. Hypophosphatemic osteomalacia was diagnosed from a low serum phosphorus level, 1,25-dihydroxyvitamin D3 level, high levels of bone specific alkaline phosphatase and the findings of bone scintigraphy, although a bone biopsy was not performed. Twenty four hour urine demonstrated a low renal fractional tubular reabsorption of phosphate, increased fractional excretion of uric acid and generalized aminoaciduria. An intravenous bicarbonate loading test suggested the presence of proximal renal tubular acidosis (RTA). These biochemical data indicated Fanconi syndrome with proximal RTA. A kidney biopsy demonstrated the features of tubulointerstitial nephritis (TIN). The patient was also suspected as having primary biliary cirrhosis (PBC) because of high levels of alkaline phosphatase, IgM and the presence of anti-mitochondrial M2 antibody, though biochemical liver function was normal. Sequential liver biopsy was compatible with PBC and the diagnosis of PBC was definite. After administration of 1,25 dihydroxyvitamin D3, neutral potassium phosphate, sodium bicarbonate for osteomalacia and subsequent predonizolone for TIN, symptoms of fractures were relieved and renal function including Fanconi syndrome was ameliorated. In this case, asymptomatic PBC was shown to induce TIN with Fanconi syndrome with dysregulation of electrolytes and vitamin D metabolism, which in turn led to osteomalacia with multiple fractures. Osteomalacia has not been recognized as a result of the renal involvement of PBC. PBC and its rare complication of TIN with Fanconi syndrome should be considered in adult patients with unexplained osteomalacia even in the absence of liver dysfunction.

Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Young C.; Yim, Hye K.; Jung, Young S.

2007-08-15

Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomymore » also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards.« less

All That Glitters Yellow Is Not Gold: Presentation and Pathophysiology of Bile Cast Nephropathy.

PubMed

Pitlick, Mitchell; Rastogi, Prerna

2017-10-01

Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice. It is characterized by the presence of bile casts in renal tubules, which can possibly cause tubular injury through obstructive and direct toxic effects. Thus, AKI in patients with liver disease may have a structural component in addition to a functional one. In this study, we describe 2 patients with severe hyperbilirubinemia who developed AKI and underwent a kidney biopsy that revealed bile casts in tubular lumens, consistent with bile cast nephropathy. One patient was treated aggressively for alcoholic hepatitis and required hemodialysis for AKI. The second patient was treated conservatively for drug-induced liver injury and did not require dialysis. Both patients saw a reduction in their bilirubin and creatinine toward baseline. Bile cast nephropathy is an important pathological entity that may account for the renal dysfunction in some patients with liver disease. It requires kidney biopsy for diagnosis and may often be overlooked given the scarcity of kidney biopsy in this particular clinical setting. The etiology is multifactorial, and it is often difficult to predict without the aid of a renal biopsy.

Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.

PubMed

TruneČka, P; Klempnauer, J; Bechstein, W O; Pirenne, J; Friman, S; Zhao, A; Isoniemi, H; Rostaing, L; Settmacher, U; Mönch, C; Brown, M; Undre, N; Tisone, G

2015-07-01

DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals Inc.

An analysis of the differences between early and late preeclampsia with severe hypertension.

PubMed

Li, X L; Guo, P L; Xue, Y; Gou, W L; Tong, M; Chen, Q

2016-01-01

Preeclampsia is clinically divided into early onset and late onset preeclampsia based on the gestational age at delivery. Although the diagnostic criteria are the same in each subgroup of preeclampsia, it has been suggested that the maternal and perinatal mortalities of early onset and late onset preeclampsia are different. However, studies that compare clinical parameters or laboratory biomarkers between early onset and late onset preeclampsia are limited. Data on 177 women with early or late preeclampsia with severe hypertension were collected from a University Teaching Hospital from January 2010 to January 2011 and analysed. Data included all the clinical parameters and laboratory biomarkers of liver and renal function. 63 women and 114 women were diagnosed with early and late preeclampsia with severe hypertension, respectively. There was no difference in the maternal age and the incidence of clinical symptoms including edema, vision disturbance, severe headache and stillbirth between two groups. There was a decrease in alkaline phosphatase levels in early preeclampsia with severe hypertension but other markers of liver function were not altered. However, renal function including blood urea nitrogen, creatinine and uric acid were significantly higher in early preeclampsia with severe hypertension. Umbilical artery systolic velocity/diastolic velocity ratio was significantly higher in early preeclampsia with severe hypertension. Our data demonstrates that the laboratory biomarkers of renal function differ between early and late preeclampsia with severe hypertension. The severity of renal dysfunction correlated with the time of delivery in preeclampsia with severe hypertension. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

A PET Tracer for Renal Organic Cation Transporters, ¹¹C-Metformin: Radiosynthesis and Preclinical Proof-of-Concept Studies.

PubMed

Jakobsen, Steen; Busk, Morten; Jensen, Jonas Brorson; Munk, Ole Lajord; Zois, Nora Elisabeth; Alstrup, Aage K O; Jessen, Niels; Frøkiær, Jørgen

2016-04-01

Organic cation transporters (OCTs) in the kidney proximal tubule (PT) participate in renal excretion of drugs and endogenous compounds. PT function is commonly impaired in kidney diseases, and consequently quantitative measurement of OCT function may provide an important estimate of kidney function. Metformin is a widely used drug and targets OCT type 2 located in the PT. Thus, we hypothesized that (11)C-labeled metformin would be a suitable PET tracer for quantification of renal function. (11)C-metformin was prepared by (11)C-methylation of 1-methylbiguanide. In vitro cell uptake of (11)C-metformin was studied in LLC-PK1 cells in the presence of increasing doses of unlabeled metformin. In vivo small-animal PET studies in Sprague-Dawley rats were performed at baseline and after treatment with OCT inhibitors to evaluate renal uptake of (11)C-metformin. Kidney and liver pharmacokinetics of (11)C-metformin was investigated in vivo by dynamic (11)C-metformin PET/CT in 6 anesthetized pigs, and renal clearance of (11)C-metformin was compared with renal clearance of (51)Cr-ethylenediaminetetraacetic acid (EDTA). Formation of (11)C metabolites was investigated by analysis of blood and urine samples. The radiochemical yield of (11)C-metformin was 15% ± 3% (n= 40, decay-corrected), and up to 1.5 GBq of tracer were produced with a radiochemical purity greater than 95% in less than 30 min. Dose-dependent uptake of (11)C-metformin in LLC-PK1 cells was rapid. Rat small-animal PET images showed (11)C-metformin uptake in the kidney and liver, the kinetics of which were changed after challenging animals with OCT inhibitors. In pigs, 80% of the injected metformin dose was rapidly present in the kidney, and a high dose of metformin caused a delayed renal uptake and clearance compared with baseline consistent with transporter-mediated competition. Renal clearance of (11)C-metformin was approximately 3 times the renal clearance of (51)Cr-EDTA. We successfully synthesized an (11)C-metformin tracer, and PET studies in rats and pigs showed a rapid kidney uptake from the blood and excretion into the bladder similar to other radiopharmaceuticals developed for γ-camera renography. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chronic effects of soft drink consumption on the health state of Wistar rats: A biochemical, genetic and histopathological study.

PubMed

Alkhedaide, Adel; Soliman, Mohamed Mohamed; Salah-Eldin, Alaa-Eldin; Ismail, Tamer Ahmed; Alshehiri, Zafer Saad; Attia, Hossam Fouad

2016-06-01

The present study was performed to examine the effects of chronic soft drink consumption (SDC) on oxidative stress, biochemical alterations, gene biomarkers and histopathology of bone, liver and kidney. Free drinking water of adult male Wistar rats was substituted with three different soft drinks: Coca‑Cola, Pepsi and 7‑Up, for three consecutive months. The serum and organs were collected for examining the biochemical parameters associated with bone, liver and kidney functions. Semi‑quantitative reverse transcription polymerase chain reaction was used to observe the changes in the expression of genes in the liver and kidney, which are associated with oxidative stress resistance. Histopathological investigations were performed to determine the changes in bone, liver and kidney tissues using hematoxylin and eosin stains. SDC affected liver, kidney and bone function biomarkers. Soft drinks increased oxidative stress, which is represented by an increase in malondialdehyde and a decrease in antioxidant levels. SDC affected serum mineral levels, particularly calcium and phosphorus. Soft drinks downregulated the expression levels of glutathione‑S‑transferase and super oxide dismutase in the liver compared with that of control rats. Rats administered Coca‑Cola exhibited a hepatic decrease in the mRNA expression of α2‑macroglobulin compared with rats administered Pepsi and 7‑Up. On the other hand, SDC increased the mRNA expression of α1‑acid glycoprotein. The present renal studies revealed that Coca‑Cola increased the mRNA expression levels of desmin, angiotensinogen and angiotensinogen receptor compared with the other groups, together with mild congestion in renal histopathology. Deleterious histopathological changes were reported predominantly in the bone and liver of the Coca‑Cola and Pepsi groups. In conclusion, a very strict caution must be considered with SDC due to the increase in oxidative stress biomarkers and disruption in the expression of certain genes associated with the bio‑vital function of both the liver and kidney.

Chronic effects of soft drink consumption on the health state of Wistar rats: A biochemical, genetic and histopathological study

PubMed Central

ALKHEDAIDE, ADEL; SOLIMAN, MOHAMED MOHAMED; SALAH-ELDIN, ALAA-ELDIN; ISMAIL, TAMER AHMED; ALSHEHIRI, ZAFER SAAD; ATTIA, HOSSAM FOUAD

2016-01-01

The present study was performed to examine the effects of chronic soft drink consumption (SDC) on oxidative stress, biochemical alterations, gene biomarkers and histopathology of bone, liver and kidney. Free drinking water of adult male Wistar rats was substituted with three different soft drinks: Coca-Cola, Pepsi and 7-Up, for three consecutive months. The serum and organs were collected for examining the biochemical parameters associated with bone, liver and kidney functions. Semi-quantitative reverse transcription polymerase chain reaction was used to observe the changes in the expression of genes in the liver and kidney, which are associated with oxidative stress resistance. Histopathological investigations were performed to determine the changes in bone, liver and kidney tissues using hematoxylin and eosin stains. SDC affected liver, kidney and bone function biomarkers. Soft drinks increased oxidative stress, which is represented by an increase in malondialdehyde and a decrease in antioxidant levels. SDC affected serum mineral levels, particularly calcium and phosphorus. Soft drinks downregulated the expression levels of glutathione-S-transferase and super oxide dismutase in the liver compared with that of control rats. Rats administered Coca-Cola exhibited a hepatic decrease in the mRNA expression of α2-macroglobulin compared with rats administered Pepsi and 7-Up. On the other hand, SDC increased the mRNA expression of α1-acid glycoprotein. The present renal studies revealed that Coca-Cola increased the mRNA expression levels of desmin, angiotensinogen and angiotensinogen receptor compared with the other groups, together with mild congestion in renal histopathology. Deleterious histopathological changes were reported predominantly in the bone and liver of the Coca-Cola and Pepsi groups. In conclusion, a very strict caution must be considered with SDC due to the increase in oxidative stress biomarkers and disruption in the expression of certain genes associated with the bio-vital function of both the liver and kidney. PMID:27121771

Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience.

PubMed

Lorenzo, V; Alvarez, A; Torres, A; Torregrosa, V; Hernández, D; Salido, E

2006-09-01

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.

Effects of creatine supplementation on biomarkers of hepatic and renal function in young trained rats.

PubMed

Souza, William Marciel; Heck, Thiago Gomes; Wronski, Evanio Castor; Ulbrich, Anderson Zampier; Boff, Everton

2013-11-01

Creatine supplementation has been widely used by athletes and young physical exercise practioneers in order of increasing muscle mass and enhancing athletic performance, but their use/overuse may represent a health risk on hepatic and renal impaired function. In this study, we evaluated the effects of 40 days of oral creatine supplementation on hepatic and renal function biomarkers in a young animal model. Wistar rats (5 weeks old) were divided in five groups (n = 7): control (CONTR), oral creatine supplementation (CREAT), moderate exercise training (EXERC), moderate exercise training plus oral creatine supplementation (EXERC + CREAT) and pathological group (positive control for liver and kidney injury) by the administration of rifampicin (RIFAMPICIN). Exercise groups were submitted to 60 min/day of swimming exercise session with a 4% of body weight workload for six weeks. The EXERC + CREAT showed the higher body weight at the end of the training protocol. The CREAT and EXERC + CREAT group showed an increase in hepatic (Aspartate transaminase and gamma-glutamyl transpeptidase) and renal (urea and creatinine) biomarkers levels (p < 0.05). Our study showed that the oral creatine supplementation promoted hepatic and renal function challenge in young rats submitted to moderate exercise training.

Impact of Impaired Renal Function on Gadolinium Retention After Administration of Gadolinium-Based Contrast Agents in a Mouse Model.

PubMed

Kartamihardja, A Adhipatria P; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito

2016-10-01

The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.

Changes in Life-Style After Liver Transplantation

PubMed Central

Zitelli, Basil J.; Miller, Joanne W.; Gartner, J. Carlton; Malatack, J. Jeffrey; Urbach, Andrew H.; Belle, Steven H.; Williams, Laurel; Kirkpatrick, Beverly; Starzl, Thomas E.

2010-01-01

Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in lifestyle. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pre-transplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients’ behavior significantly improved according to parents’ perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents’ perceptions of behavior of children appear to be improved after liver transplantation. PMID:3041361

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

NASA Astrophysics Data System (ADS)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

Ultrasound hepatic/renal ratio and hepatic attenuation rate for quantifying liver fat content.

PubMed

Zhang, Bo; Ding, Fang; Chen, Tian; Xia, Liang-Hua; Qian, Juan; Lv, Guo-Yi

2014-12-21

To establish and validate a simple quantitative assessment method for nonalcoholic fatty liver disease (NAFLD) based on a combination of the ultrasound hepatic/renal ratio and hepatic attenuation rate. A total of 170 subjects were enrolled in this study. All subjects were examined by ultrasound and (1)H-magnetic resonance spectroscopy ((1)H-MRS) on the same day. The ultrasound hepatic/renal echo-intensity ratio and ultrasound hepatic echo-intensity attenuation rate were obtained from ordinary ultrasound images using the MATLAB program. Correlation analysis revealed that the ultrasound hepatic/renal ratio and hepatic echo-intensity attenuation rate were significantly correlated with (1)H-MRS liver fat content (ultrasound hepatic/renal ratio: r = 0.952, P = 0.000; hepatic echo-intensity attenuation r = 0.850, P = 0.000). The equation for predicting liver fat content by ultrasound (quantitative ultrasound model) is: liver fat content (%) = 61.519 × ultrasound hepatic/renal ratio + 167.701 × hepatic echo-intensity attenuation rate -26.736. Spearman correlation analysis revealed that the liver fat content ratio of the quantitative ultrasound model was positively correlated with serum alanine aminotransferase, aspartate aminotransferase, and triglyceride, but negatively correlated with high density lipoprotein cholesterol. Receiver operating characteristic curve analysis revealed that the optimal point for diagnosing fatty liver was 9.15% in the quantitative ultrasound model. Furthermore, in the quantitative ultrasound model, fatty liver diagnostic sensitivity and specificity were 94.7% and 100.0%, respectively, showing that the quantitative ultrasound model was better than conventional ultrasound methods or the combined ultrasound hepatic/renal ratio and hepatic echo-intensity attenuation rate. If the (1)H-MRS liver fat content had a value < 15%, the sensitivity and specificity of the ultrasound quantitative model would be 81.4% and 100%, which still shows that using the model is better than the other methods. The quantitative ultrasound model is a simple, low-cost, and sensitive tool that can accurately assess hepatic fat content in clinical practice. It provides an easy and effective parameter for the early diagnosis of mild hepatic steatosis and evaluation of the efficacy of NAFLD treatment.

Simultaneous pancreas and kidney transplantation for liver transplant recipients with diabetes and uremia.

PubMed

Tam, Ngalei; Zhang, Chuanzhao; Lin, Jianwei; Wu, Chenglin; Deng, Ronghai; Liao, Bing; Hu, Shuiqing; Wang, Dongping; Zhu, Xiaofeng; Wu, Linwei; He, Xiaoshun

2015-06-01

Chronic kidney disease (CKD) has become a critical problem due to immunosuppressant related nephrotoxicity in liver transplant (LTx) recipients, especially in patients with pre-transplant risk factors. LTx recipients with uraemia and diabetes have poor prognosis even when treated with dialysis and insulin. Simultaneous pancreas and kidney transplantation (SPK) has been proven to be an effective treatment for patients with diabetic uraemia, but rarely performed in patients after LTx. Two cases of SPK after LTx were performed in our centre and we present our experience here. Two patients received LTx because of HBV related liver cirrhosis; both of them had pre-transplant diabetes mellitus (DM), which worsened after the administration of immunosuppressive drugs. These two patients suffered from CKD and developed uraemia due to diabetic nephropathy and immunosuppressive drugs induced renal toxicity years after LTx. They relied on dialysis and insulin injection. SPK were performed years after LTx and the clinical data was retrospectively analyzed. SPK was successfully performed in these two patients. Pancreatic fluid drainage was achieved via a side-to-side duodenojejunostomy into the proximal jejunum. No serious surgical complications, including pancreatitis or pancreatic fistula were observed postoperatively. In both cases, kidney and pancreatic grafts were functioning well as evidenced by euglycemia without the need for insulin injections and normal serum-creatinine level 7days after the operation. One of the patients presented with renal graft impairment 1week after the operation. FK506 was tapered and rapamycin was used when the renal graft biopsy indicated drug toxicity. The patient's kidney graft function recovered gradually after the adjustment. Both patients have good function of liver, kidney and pancreas grafts during a 60-month and 30-month period of follow up. SPK could serve as an effective option for patients with diabetes and uremia after LTx. Perioperative management, especially the immunosuppressive strategy is crucial to improve the outcome of this procedure. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure

PubMed Central

Dear, James W.; Leelahavanichkul, Asada; Aponte, Angel; Hu, Xuzhen; Constant, Stephanie L.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

2008-01-01

Objective Sepsis-induced multi-organ failure continues to have a high mortality. The liver is an organ central to the disease pathogenesis. The objective of this study was to identify the liver proteins that change in abundance with sepsis and, therefore, identify new drug targets. Design Proteomic discovery study and drug target validation Setting Research institute laboratory Subjects Three month old C57BL/6 mice Interventions We used a mouse model of sepsis based on cecal ligation and puncture (CLP) but with fluid and antibiotic resuscitation. Liver proteins that changed in abundance were identified by difference in-gel electrophoresis (DIGE). We compared liver proteins from 6 hr post-CLP to sham-operated mice (‘early proteins’) and 24 hr post-CLP with 6 hr post-CLP (‘late proteins’). Proteins that changed in abundance were identified by tandem mass spectrometry. We then inhibited the receptor for one protein and determined the effect on sepsis-induced organ dysfunction. Results The liver proteins that changed in abundance after sepsis had a range of functions such as acute phase proteins, coagulation, ER stress, oxidative stress, apoptosis, mitochondrial proteins and nitric oxide metabolism. We found that cyclophilin increased in abundance after CLP. When the receptor for this protein, CD147, was inhibited sepsis-induced renal dysfunction was reduced. There was also a significant reduction in serum cytokine production when CD147 was inhibited. Conclusion By applying proteomics to a clinically relevant mouse model of sepsis we identified a number of novel proteins that changed in abundance. The inhibition of the receptor for one of these proteins, cyclophilin, attenuated sepsis-induced acute renal failure. The application of proteomics to sepsis research can facilitate the discovery of new therapeutic targets. PMID:17944020

Suicidal intoxication with potassium chlorate successfully treated with renal replacement therapy and extracorporeal liver support.

PubMed

Sein Anand, Jacek; Barwina, Małgorzata; Zajac, Maciej; Kaletha, Krystian

2012-01-01

We present a case of a 22-year-old male who, in a suicide attempt, ingested approximately 200 g of potassium chlorate. Upon admission to the hospital, he presented in full respiratory failure with cyanosis. Methylene blue antidote was given but found to be ineffective. The patient was intubated and mechanical ventilation was initiated. Because of renal failure with anuria, intermittent haemodialysis (iHD) followed by continuous venovenous hemodiafiltration (CVVHDF) was performed. His hospital stay was also complicated by hemolysis, disseminated intravascular coagulation, and atrial fibrillation. Transfusions of packed red blood cells, platelets, and fresh frozen plasma were necessary to correct the deficits. He also developed liver failure and required two sessions of molecular adsorbent recirculating system (MARS) therapy. On day 14 of his hospitalization, he regained consciousness, as well as full respiratory and circulatory function. There are no controlled studies addressing management of potassium chlorate poisoning. We suggest that early renal replacement therapy should be strongly considered.

Nephrogenic Systemic Fibrosis Risk After Liver Magnetic Resonance Imaging With Gadoxetate Disodium in Patients With Moderate to Severe Renal Impairment

PubMed Central

Lauenstein, Thomas; Ramirez-Garrido, Francisco; Kim, Young Hoon; Rha, Sung Eun; Ricke, Jens; Phongkitkarun, Sith; Boettcher, Joachim; Gupta, Rajan T.; Korpraphong, Pornpim; Tanomkiat, Wiwatana; Furtner, Julia; Liu, Peter S.; Henry, Maren; Endrikat, Jan

2015-01-01

Objective The objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment. Materials and Methods We performed a prospective, multicenter, nonrandomized, open-label phase 4 study in 35 centers from May 2009 to July 2013. The study population consisted of patients with moderate to severe renal impairment scheduled for liver imaging with gadoxetate disodium. All patients received a single intravenous bolus injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 357 patients were included, with 85 patients with severe and 193 patients with moderate renal impairment, which were the clinically most relevant groups. The mean time period from diagnosis of renal disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the moderate and severe renal impairment cohort, respectively. Overall, 101 patients (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI contrast agents within 12 months before the start of the study or in the follow-up. No patient developed symptoms conclusive of NSF within the 2-year follow-up. Conclusions Gadoxetate disodium in patients with moderate to severe renal impairment did not raise any clinically significant safety concern. No NSF cases were observed. PMID:25756684

Chemical composition and biological evaluation of Physalis peruviana root as hepato-renal protective agent.

PubMed

El-Gengaihi, Souad E; Hassan, Emad E; Hamed, Manal A; Zahran, Hanan G; Mohammed, Mona A

2013-03-01

This study was designed to investigate the potential of Physalis peruviana root as a functional food with hepato-renal protective effects against fibrosis. The chemical composition of the plant root suggested the presence of alkaloids, withanolides and flavonoids. Five compounds were isolated and their structures elucidated by different spectral analysis techniques. One compound was isolated from the roots: cuscohygrine. The biological evaluation was conducted on different animal groups; control rats, control treated with ethanolic root extract, CCl(4) group, CCl(4) treated with root extract, and CCl(4) treated with silymarin as a standard herbal drug. The evaluation used the oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO). The liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea, and serum protein were also evaluated. The results suggested safe administration, and improvement of all the investigated parameters. The liver and kidney histopathological analysis confirmed the results. In conclusion, P. peruviana succeeded in protecting the liver and kidney against fibrosis. Further studies are needed to discern their pharmacological applications and clinical uses.

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats.

PubMed

Kandasamy, Neelamegam; Ashokkumar, Natarajan

2014-09-01

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Tumor-Like Liver Abscess Mimicking Malignancy With Lung Metastases in a Patient With Acute Renal Failure: A Case Report.

PubMed

Wang, Chih Hsin; Sun, Cheuk-Kay; Jiang, Jiunn-Song; Tsai, Ming Hsien

2016-03-01

The worldwide incidence of Klebsiella pneumoniae liver abscess (KLA) is increasing. It is important to accurately diagnose this life-threatening disease to provide timely and appropriate treatment. Here we report the case of a 38-year-old man with acute renal failure and a tumor-like liver abscess and septic pulmonary embolism. Initially, his clinical symptoms, laboratory tests, and radiological findings presented equivocal results of malignancy with metastases. Fine needle aspiration of liver tumor was performed, which showed purulent material with a culture positive for K pneumoniae. KLA symptoms are atypical, and radiological findings may mimic a malignancy with tumor necrosis. In some circumstances, liver aspiration biopsy may be necessary to confirm the real etiology, leading to prompt and timely treatment. Moreover, we should be alert for the impression of KLA when facing a diabetic patient with liver mass lesion and acute renal failure.

Tumor-Like Liver Abscess Mimicking Malignancy With Lung Metastases in a Patient With Acute Renal Failure

PubMed Central

Wang, Chih Hsin; Sun, Cheuk-Kay; Jiang, Jiunn-Song; Tsai, Ming Hsien

2016-01-01

Abstract The worldwide incidence of Klebsiella pneumoniae liver abscess (KLA) is increasing. It is important to accurately diagnose this life-threatening disease to provide timely and appropriate treatment. Here we report the case of a 38-year-old man with acute renal failure and a tumor-like liver abscess and septic pulmonary embolism. Initially, his clinical symptoms, laboratory tests, and radiological findings presented equivocal results of malignancy with metastases. Fine needle aspiration of liver tumor was performed, which showed purulent material with a culture positive for K pneumoniae. KLA symptoms are atypical, and radiological findings may mimic a malignancy with tumor necrosis. In some circumstances, liver aspiration biopsy may be necessary to confirm the real etiology, leading to prompt and timely treatment. Moreover, we should be alert for the impression of KLA when facing a diabetic patient with liver mass lesion and acute renal failure. PMID:26986170

Neonatal diabetes mellitus, congenital hypothyroidism, hepatic fibrosis, polycystic kidneys, and congenital glaucoma: a new autosomal recessive syndrome?

PubMed

Taha, Doris; Barbar, Maha; Kanaan, Hassan; Williamson Balfe, John

2003-10-15

We report on two sibs (of 4) with a syndrome of minor facial anomalies, proportionate IUGR, neonatal non-autoimmune diabetes mellitus (NDM), severe congenital hypothyroidism (CH), cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by large kidneys and multiple small cysts with deficient corticomedullary junction differentiation and normal kidney function. The phenotype observed in the two sibs was identical. Although a combination of liver, kidney, and pancreatic involvement has been described in Ivemark syndrome (hepato-renal-pancreatic syndrome), the coexistence of NDM, CH, and glaucoma in both sibs suggests the possibility that this combination of manifestations describes a new autosomal recessive syndrome. Mutation analysis for several candidate genes is warranted. Copyright 2003 Wiley-Liss, Inc.

The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney

PubMed Central

Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

2017-01-01

Objective: Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger (Zingiber officinale) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. Materials and Methods: The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Results: Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. Conclusion: In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron. PMID:29299437

The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney.

PubMed

Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

2017-01-01

Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger ( Zingiber officinale ) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron.

Liver disease in autosomal recessive polycystic kidney disease: clinical characteristics and management in relation to renal failure.

PubMed

Luoto, Topi T; Pakarinen, Mikko P; Jahnukainen, Timo; Jalanko, Hannu

2014-08-01

We correlated liver and kidney manifestations in a national cohort of patients with autosomal recessive polycystic kidney disease (ARPKD). A total of 27 consecutive patients with ARPKD were included. Hepatobiliary disorders were comparatively evaluated in 2 groups: children in group 1 (n = 10) displayed renal failure as infants and those in group 2 (n = 17) had normal kidney function through the first year of life. Median follow-up time was 10.6 (range, 0.4-40) years. Portal hypertension was diagnosed in 13 patients (48%) at the median age 5.0 (1.5-27.9) years. Esophageal varices developed in 8 patients (30%) at age 8.0 (2.1-11.9) years; 4 patients (15%) had variceal bleeding, and hypersplenism/splenomegaly occurred in 52%, similarly in both groups. Biliary tract dilatation was detected at 2.8 years in group 1 and at 7.9 years in group 2, significantly more frequently in group 1 (60% vs 18%, P = 0.039), causing cholangitis in 2 (20%) versus none in group 2 (P = 0.055). A total of 10 patients (37%) underwent cadaveric liver transplantation (LT) at a median age of 6.6 (1.0-20.0) years. In 1 patient LT was performed because of hepatoblastoma. Nine of these were combined liver-kidney transplantations (CLKT). Patients in group 1 required LT earlier (4.1 years vs 18.2 years, P = 0.017) and more frequently (70% vs 18%, P = 0.01). Overall survival beyond neonatal period was 85%. Two patients died because of infectious complications after CLKT, and 1 patient because of recurrent hepatoblastoma. Although correlation of renal and liver manifestations was variable, biliary dilatation was associated with early renal failure. CLKT may be a treatment for patients with ARPKD with marked hepatobiliary complications.

Acute on chronic liver failure in a patient with sickle cell anaemia (HbSS)

PubMed Central

Im, Dana DaEun; Essien, Utibe; DePasse, Jacqueline W; Chiappa, Victor

2015-01-01

A man in his late 40s with sickle cell anaemia (HbSS) presented to the emergency department with 2 weeks of diffuse oedema, increased abdominal girth and dyspnoea. His anasarca was thought to be indicative of an acute decompensation of his known liver cirrhosis with transfusion-induced haemosiderosis. While his anasarca improved with diuresis, his direct hyperbilirubinaemia suddenly worsened without any signs of haemolysis, biliary disease or obstruction. He also developed an acute worsening in serum creatinine (1.17–7.0 mg/dL in 7 days) despite subsequent treatment for presumed hepatorenal syndrome (HRS). Given his clinical decline, the patient's goals of care were transitioned to comfort measures only. His clinical presentation and rapid liver and renal deterioration were most typical of sickle cell intrahepatic cholestasis (SCIC). SCIC can lead to rapid deterioration in renal function and can be mistaken for HRS. When SCIC is suspected, consideration of exchange transfusions should be made early. PMID:26135492

Nonsteroidal Anti-Inflammatory Drugs and the Kidney

PubMed Central

Hörl, Walter H.

2010-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result. PMID:27713354

Morin Hydrate Mitigates Cisplatin-Induced Renal and Hepatic Injury by Impeding Oxidative/Nitrosative Stress and Inflammation in Mice.

PubMed

K V, Athira; Madhana, Rajaram Mohanrao; Kasala, Eshvendar Reddy; Samudrala, Pavan Kumar; Lahkar, Mangala; Gogoi, Ranadeep

2016-12-01

Cisplatin is a widely used chemotherapeutic drug; however, it induces damage on kidney and liver at clinically effective higher doses. Morin hydrate possesses antioxidant, anti-inflammatory, and anticancer properties. Therefore, we aimed to investigate the effects of morin hydrate (50 and 100 mg/kg, orally) against the renohepatic toxicity induced by a high dose of cisplatin (20 mg/kg, intraperitoneally). Renal and hepatic function, oxidative/nitrosative stress, and inflammatory markers along with histopathology were evaluated. Morin hydrate ameliorated cisplatin-induced renohepatic toxicity significantly at 100 mg/kg as evidenced from the significant reversal of cisplatin-induced body weight loss, mortality, functional and structural alterations of kidney, and liver. The protective role offered by morin hydrate against cisplatin-induced renohepatic toxicity is by virtue of its free radical scavenging property, thereby abating the depletion of cellular antioxidant defense components and through modulation of inflammatory cytokines. We speculate morin hydrate as a protective candidate against renohepatic toxicity of cisplatin. © 2016 Wiley Periodicals, Inc.

Treatment With Human Wharton’s Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction

PubMed Central

Cóndor, José M.; Rodrigues, Camila E.; de Sousa Moreira, Roberto; Canale, Daniele; Volpini, Rildo A.; Shimizu, Maria H.M.; Camara, Niels O.S.; Noronha, Irene de L.

2016-01-01

The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and rats submitted to CLP and intraperitoneally injected, 6 hours later, with 1 × 106 WJ-MSCs. The glomerular filtration rate (GFR) was measured at 6 and 24 hours after CLP or sham surgery. All other studies were conducted at 24 hours after CLP or sham surgery. By 6 hours, GFR had decreased in the CLP rats. At 24 hours, Klotho renal expression significantly decreased. Treatment with WJ-MSCs improved the GFR; improved tubular function; decreased the CD68-positive cell count; decreased the fractional interstitial area; decreased expression of nuclear factor κB and of cytokines; increased expression of eNOS, vascular endothelial growth factor, and Klotho; attenuated renal apoptosis; ameliorated hepatic function; increased glycogen deposition in the liver; and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. Klotho protein expression was higher in WJ-MSCs than in human adipose-derived MSCs. Because WJ-MSCs preserve renal and hepatic function, they might play a protective role in sepsis. Significance Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor κB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. PMID:27280799

Successful Transplant of Two Kidneys Harvested from a Young Brain-Dead Liver Transplant Recipient.

PubMed

Rana, Anil Kumar Singh; Agarwal, Nitin; Dutta, Sushant; Dokania, Manoj Kumar

2017-06-01

Efforts to increase the dismal deceased renal transplantation (DRT): live renal transplantation (LRT) ratio in our country have gathered momentum recently, with governmental and non-governmental projects focussing on building public awareness and capacity-building, and appropriate legislation. Worldwide, efforts at increasing the number of organs from the deceased pool have focussed on the use of 'expanded criteria donors', including deceased cardiac donors (DCD). 'Reuse' transplant, where an organ is transplanted after removal from the first recipient, is a rare strategy, used more commonly in liver than in kidney transplantation. Exceptional circumstances, where other organs have been harvested from transplant recipients, are rare. We describe the successful transplants of two renal grafts obtained from a 19-year-old brain-dead liver transplant recipient; this is probably the second case in English-language literature. A 19-year-old male patient with hepatitis E-induced fulminant hepatic failure underwent live-related liver transplantation. On postoperative day 2, cerebral edema set in, and the patient was declared brain-dead. Despite the economical and emotional trauma, the family opted for donation of the well-perfused kidneys. The kidneys were transported in HTK solution (histidine-tryptophan-ketoglutarate) to our centre. Recipient 1 was a 32-year-old woman (B positive) and recipient 2 was a 29-year-old man (also B positive); the kidneys were placed extraperitoneally and anastomosed end-to-side to the external iliac artery and vein. Recipient 2 experienced delayed graft function; however, both are doing well 15 months posttransplant.

Liver Metastases From Renal Oncocytoma With Vascular Extension.

PubMed

Cacciamani, Giovanni; Cima, Luca; Ficial, Miriam; Novella, Giovanni; Siracusano, Salvatore; Tedeschi, Umberto; Balzarro, Matteo; Montin, Umberto; Cerruto, Maria A; De Marco, Vincenzo; Porcaro, Antonio B; Hes, Ondrej; DʼErrico, Antonia; Martignoni, Guido; Ghimenton, Claudio; Zaza, Gianluigi; Artibani, Walter; Brunelli, Matteo; Eccher, Albino

2017-07-04

The 2016 World Health Organization Renal Tumor Classification defines renal oncocytoma (RO) as a benign epithelial tumor; however, malignant histopathologic features have been documented. Rare cases with metastases have been reported. We describe the case of a 62-year-old woman who was referred to the Urology Clinic for a routine work-up. Magnetic resonance imaging and computerized tomography showed a 7-cm mass in the middle and lower portions of the left kidney and 2 suspected liver metastases. The patient underwent surgery. Microscopically both renal and liver lesions presented solid, solid-nested, and microcystic architecture, composed predominantly of large eosinophilic cells without any worrisome pattern except the vascular extension. The cells were positive for S100A1, CD117, and PAX-8 and negative for CAIX, CK7, and AMACR. Fluorescence in situ hybridization showed a disomic profile for the chromosomes 1, 2, 6, 7, 10, 17. No mutation of coding sequence of the SDHB, SDHC, SDHD, VHL, and BHD genes and no loss of heterozygosity at 3p were found. The final diagnosis was "RO" according to the 2016 World Health Organization Renal Tumor Classification with "liver metastases." This report provides a wide clinical-pathologic, immunophenotypical and molecular documentation of a RO with liver metastases.

Simultaneous evaluation of renal morphology and function in live kidney donors using dynamic magnetic resonance imaging.

PubMed

Artunc, F; Yildiz, S; Rossi, C; Boss, A; Dittmann, H; Schlemmer, H P; Risler, T; Heyne, N

2010-06-01

Evaluation of potential kidney donors requires the assessment of both kidney anatomy and function. In this prospective study, we sought to expand the diagnostic yield of magnetic resonance (MR) by adding functional measurements of glomerular filtration rate (GFR) and split renal function. Between 2007 and 2009, all potential kidney donors presenting to our facility underwent a comprehensive single-stop MR study that included an assessment of anatomy, angiography and functional measurements. GFR was measured after a bolus injection of gadobutrol (4 ml, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. Split renal function was calculated from the increase of signal intensity over the renal cortex. Values were compared to renal scintigraphy with (99m)Tc-DTPA from the same day. The MR investigation was successfully performed in 21 participants. The GFR derived from MR (MR-GFR) correlated well (r = 0.84) with the GFR derived from scintigraphy (DTPA-GFR). The mean value of the paired differences was 4 +/- 13 [SD] ml/min/1.73 m(2) and was not significantly different from zero. The ratio between right and left kidney function was similar with both techniques (1.01 +/- 0.17 with MR and 1.06 +/- 0.12 with scintigraphy, P = 0.20). We demonstrate an MR-based approach to comprehensively evaluate both kidney anatomy and function in a single investigation, thereby facilitating the evaluation of potential kidney donors.

46 CFR 197.560 - Medical surveillance.

Code of Federal Regulations, 2014 CFR

2014-10-01

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46 CFR 197.560 - Medical surveillance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Medical surveillance. 197.560 Section 197.560 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS..., and abnormal functions of formed blood elements, a history of renal or liver dysfunction, a history of...

46 CFR 197.560 - Medical surveillance.

Code of Federal Regulations, 2012 CFR

2012-10-01

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46 CFR 197.560 - Medical surveillance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Medical surveillance. 197.560 Section 197.560 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS..., and abnormal functions of formed blood elements, a history of renal or liver dysfunction, a history of...

46 CFR 197.560 - Medical surveillance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Medical surveillance. 197.560 Section 197.560 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS..., and abnormal functions of formed blood elements, a history of renal or liver dysfunction, a history of...

Anesthetic biotransformation and renal function in obese patients during and after methoxyflurane or halothane anesthesia.

PubMed

Young, S R; Stoelting, R K; Peterson, C; Madura, J A

1975-04-01

Anesthetic biotransformation and renal function were studied in obese adult patients (148 plus or minus 8 kg; mean plus or minus SE) anesthetized for three hours with 60 per cent nitrous oxide plus either methoxyflurane or halothane for elective jejunoileal small-bowel-bypass operations. There was no evidence of persistent renal dysfunction in any patient postoperatively, but serum osmolality was elevated 72 hours after methoxyflurane anesthesia. Urine concentrating ability was not determined. Peak serum ionic fluoride concentration was 55.8 plus or minus 5.8 muM/1 two hours after discontinuation of methoxyflurane. Urinary ionic fluoride and oxalate excretions increased postoperatively. Compared with previously reported data from nonobese patients, serum ionic fluoride concentrations in obese patients increased more rapidly during methoxyflurane anesthesia and peaked higher and sooner after discontinuation of methoxyflurane. The peak serum ionic fluoride concentration was 10.4 plus or minus 1.5 muM/1 at the conclusion of halothane anesthesia, significantly more than the corresponding value in nonobese patients. Intraoperative liver biopsies from 23 of 27 patients showed moderate to severe fatty metamorphosis. Fatty liver infiltration may have increased hepatic anesthetic uptake and exposed more methoxyflurane or halothane to hepatic microsomal enzymes. The more rapid elevation and higher peak levels of serum ionic fluoride following methoxyflurane, and to a lesser extent following halothane, may reflect increased anesthetic biotransformation in obese compared with nonobese patients. To avoid excessive serum ionic fluoride elevations the authors recommended limiting low-dose methoxyflurane anesthesia delivered to obese patients with potential fatty liver infiltration to no more than three hours.

Case report: fatal poisoning with Colchicum autumnale.

PubMed

Brvar, Miran; Ploj, Tom; Kozelj, Gordana; Mozina, Martin; Noc, Marko; Bunc, Matjaz

2004-02-01

Colchicum autumnale, commonly known as the autumn crocus, contains alkaloid colchicine with antimitotic properties. A 76-year-old man with a history of alcoholic liver disease and renal insufficiency, who mistakenly ingested Colchicum autumnale instead of wild garlic (Aliium ursinum), presented with nausea, vomiting and diarrhea 12 hours after ingestion. On admission the patient had laboratory signs of dehydration. On the second day the patient became somnolent and developed respiratory insufficiency. The echocardiogram showed heart dilatation with diffuse hypokinesia with positive troponin I. The respiratory insufficiency was further deteriorated by pneumonia, confirmed by chest X-ray and later on by autopsy. Laboratory tests also revealed rhabdomyolysis, coagulopathy and deterioration of renal function and hepatic function. The toxicological analysis disclosed colchicine in the patient's urine (6 microgram/l) and serum (9 microgram/l) on the second day. Therapy was supportive with hydration, vasopressors, mechanical ventilation and antibiotics. On the third day the patient died due to asystolic cardiac arrest. Colchicine poisoning should be considered in patients with gastroenterocolitis after a meal of wild plants. Management includes only intensive support therapy. A more severe clinical presentation should be expected in patients with pre-existing liver and renal diseases. The main reasons for death are cardiovascular collapse, respiratory failure and leukopenia with infection.

Febuxostat-induced agranulocytosis in an end-stage renal disease patient: A case report.

PubMed

Poh, Xue Er; Lee, Chien-Te; Pei, Sung-Nan

2017-01-01

Febuxostat, a nonpurine xanthine oxidase inhibitor, is approved as the first-line urate-lowering therapy in gout patients with normal renal function or mild to moderate renal impairment. The most common adverse effects of febuxostat are liver function test abnormalities, diarrhea, and skin rash. However, there is insufficient data in patients with severe renal impairment and end-stage renal disease (ESRD). We report the first case, to our knowledge, in which agranulocytosis developed after febuxostat treatment in an ESRD patient. A 67-year-old woman with gout and ESRD received febuxostat 40 mg a day for 2.5 months. She subsequently complicated with febrile neutropenia and the absolute neutrophil count was only 14/μL. After broad-spectrum antibiotics treatment and no more exposure to febuxostat for 17 days, her infection and neutrophil count recovered. Bone marrow study during neutropenic period showed myeloid hypoplasia without evidence of hematologic neoplasms. As febuxostat use may become more common in the population of advanced renal failure, clinicians should be aware of this rare but potentially life-threatening adverse effect. Based on our experience, close monitoring hemogram and immediate discontinuation of this medication may prevent serious consequences.

Febuxostat-induced agranulocytosis in an end-stage renal disease patient

PubMed Central

Poh, Xue Er; Lee, Chien-Te; Pei, Sung-Nan

2017-01-01

Abstract Introduction: Febuxostat, a nonpurine xanthine oxidase inhibitor, is approved as the first-line urate-lowering therapy in gout patients with normal renal function or mild to moderate renal impairment. The most common adverse effects of febuxostat are liver function test abnormalities, diarrhea, and skin rash. However, there is insufficient data in patients with severe renal impairment and end-stage renal disease (ESRD). We report the first case, to our knowledge, in which agranulocytosis developed after febuxostat treatment in an ESRD patient. Clinical presentation: A 67-year-old woman with gout and ESRD received febuxostat 40 mg a day for 2.5 months. She subsequently complicated with febrile neutropenia and the absolute neutrophil count was only 14/μL. After broad-spectrum antibiotics treatment and no more exposure to febuxostat for 17 days, her infection and neutrophil count recovered. Bone marrow study during neutropenic period showed myeloid hypoplasia without evidence of hematologic neoplasms. Conclusion: As febuxostat use may become more common in the population of advanced renal failure, clinicians should be aware of this rare but potentially life-threatening adverse effect. Based on our experience, close monitoring hemogram and immediate discontinuation of this medication may prevent serious consequences. PMID:28079821

Piggyback technique in adult orthotopic liver transplantation: an analysis of 1067 liver transplants at a single center

PubMed Central

Nakamura, Noboru; Vaidya, Anil; Levi, David M.; Kato, Tomoaki; Nery, Jose R.; Madariaga, Juan R.; Molina, Enrique; Ruiz, Phillip; Gyamfi, Anthony; Tzakis, Andreas G.

2006-01-01

Background. Orthotopic liver transplantation (OLT) in adult patients has traditionally been performed using conventional caval reconstruction technique (CV) with veno-venous bypass. Recently, the piggyback technique (PB) without veno-venous bypass has begun to be widely used. The aim of this study was to assess the effect of routine use of PB on OLTs in adult patients. Patients and methods. A retrospective analysis was undertaken of 1067 orthotopic cadaveric whole liver transplantations in adult patients treated between June 1994 and July 2001. PB was used as the routine procedure. Patient demographics, factors including cold ischemia time (CIT), warm ischemia time (WIT), operative time, transfusions, blood loss, and postoperative results were assessed. The effects of clinical factors on graft survival were assessed by univariate and multivariate analyses.In all, 918 transplantations (86%) were performed with PB. Blood transfusion, WIT, and usage of veno-venous bypass were less with PB. Seventy-five (8.3%) cases with PB had refractory ascites following OLT (p=NS). Five venous outflow stenosis cases (0.54%) with PB were noted (p=NS). The liver and renal function during the postoperative periods was similar. Overall 1-, 3-, and 5-year patient survival rates were 85%, 78%, and 72% with PB. Univariate analysis showed that cava reconstruction method, CIT, WIT, amount of transfusion, length of hospital stay, donor age, and tumor presence were significant factors influencing graft survival. Multivariate analysis further reinforced the fact that CIT, donor age, amount of transfusion, and hospital stay were prognostic factors for graft survival. Conclusions. PB can be performed safely in the majority of adult OLTs. Results of OLT with PB are as same as for CV. Liver function, renal function, morbidity, mortality, and patient and graft survival are similar to CV. However, amount of transfusion, WIT, and use of veno-venous bypass are less with PB. PMID:18333273

Echocardiography and NAFLD (non-alcoholic fatty liver disease).

PubMed

Trovato, Francesca M; Martines, Giuseppe F; Catalano, Daniela; Musumeci, Giuseppe; Pirri, Clara; Trovato, Guglielmo M

2016-10-15

Non-alcoholic-fatty-liver-disease (NAFLD) is associated with atherosclerosis, increased cardiovascular risks and mortality. We investigated if, independently of insulin resistance, diet, physical activity and obesity, fatty liver involvement has any relationship with echocardiographic measurements in NAFLD. 660 NAFLD and 791 non-NAFLD subjects, referred to the same out-patients medical unit for lifestyle-nutritional prescription, were studied. Congestive heart failure, myocardial infarction, malignancies, diabetes mellitus, extreme obesity, underweight-bad-nourished subjects and renal insufficiency were exclusion criteria. Liver steatosis was assessed by Ultrasound-Bright-Liver-Score (BLS), left ventricular ejection fraction (LVEF), trans-mitral E/A doppler ratio (diastolic relaxation) and left ventricular myocardial mass (LVMM/m(2)) by echocardiography. Doppler Renal artery Resistive Index (RRI), insulin resistance (HOMA) and lifestyle profile were also included in the clinical assessment. LVMM/m(2) is significantly greater in NAFLD, 101.62±34.48 vs. 88.22±25.61, p<0.0001 both in men and in women. Ejection fraction is slightly smaller only in men with NAFLD; no significant difference was observed for the E/A ratio. BMI (30.42±5.49 vs. 24.87±3.81; p<0.0001) and HOMA (2.90±1.70 vs. 1.85±1.25; p: 0.0001) were significantly greater in NAFLD patients. By Multiple-Linear-Regression, NAFLD and unhealthy dietary profile are associated also in lean non-diabetic subjects with lower systolic function, independently of BMI, dietary profile, physical activity, RRI and insulin resistance. NAFLD may be a meaningful early clue suggestive of diminishing heart function, with similar determining factors. NAFLD is amenable to management and improvement by lifestyle change counseling, addressing a dual target: reducing fatty liver, which is easily monitored by ultrasound, and, independently, maintaining a normal heart function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fulminant Liver Failure in a Child With β-Thalassemia on Deferasirox: A Case Report.

PubMed

Ramaswami, Archie; Rosen, Danya J; Chu, Jaime; Wistinghausen, Birte; Arnon, Ronen

2017-04-01

Deferesirox (DFX), an oral chelating agent, is used to treat chronic iron overload in several hematological diseases such as β-thalassemia, sickle cell disease, and myelodysplastic anemia. DFX is generally well tolerated with the exception of gastrointestinal disturbances and rash, although cases of renal toxicity, as well as acute and chronic liver failure, have been reported in adults and children. Here we describe a 3-year-old girl with β-thalassemia undergoing treatment with DFX who presented with acute liver failure and Fanconi's syndrome. It is important for pediatric gastroenterologists, hepatologists, and hematologists to be aware that the commonly used drug DFX can lead to acute liver failure in children, and liver function should be monitored closely in all patients taking DFX.

Diabetes mellitus and renal involvement in chronic viral liver disease.

PubMed

Iovanescu, V F; Streba, C T; Ionescu, M; Constantinescu, A F; Vere, C C; Rogoveanu, I; Moța, E

2015-01-01

Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013<0.05) and presence of hepatitis C virus were particularly correlated with the presence of diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with HCC and none of them presented diabetes mellitus. Our study revealed that there is a significant association between diabetes mellitus and chronic viral liver disease induced by hepatitis C virus. Glomerulonephritis was the most common type of renal disease in both hepatitis patients and in those with cirrhosis. Glomerular injury was strongly correlated with the presence of hepatitis C virus than with hepatitis B virus. A connection between diabetes mellitus and hepatocellular carcinoma could not be established.

Histological Spectrum of Idiopathic Noncirrhotic Portal Hypertension in Liver Biopsies From Dialysis Patients.

PubMed

Lee, Hwajeong; Ainechi, Sanaz; Singh, Mandeep; Ells, Peter F; Sheehan, Christine E; Lin, Jingmei

2015-09-01

Liver biopsy is performed for various indications in dialysis patients. Being a less-common subset, the hepatic pathology in renal dialysis is not well documented. Idiopathic noncirrhotic portal hypertension (INCPH) is a clinical entity associated with unexplained portal hypertension and/or a spectrum of histopathological vascular changes in the liver. After encountering INCPH and vascular changes of INCPH in 2 renal dialysis patients, we sought to further investigate this noteworthy association. A random search for patients on hemodialysis or peritoneal dialysis with liver biopsy was performed. Hematoxylin and eosin, reticulin, trichrome, and CK7 stains were performed on formalin-fixed, paraffin-embedded tissue sections. Histopathological features were reviewed, and the results were correlated with clinical findings. In all, 13 liver biopsies were retrieved. The mean cumulative duration of dialysis was 50 months (range = 17 months to 11 years). All patients had multiple comorbidities. Indications for biopsy were a combination of abnormal liver function tests (6), portal hypertension (4), ascites (3), and possible cirrhosis (3). Two patients with portal hypertension underwent multiple liver biopsies for diagnostic purposes. All (100%) biopsies showed some histological features of INCPH, including narrowed portal venous lumen (9), increased portal vascular channels (8), shunt vessels (3), dilated sinusoids (9), regenerative nodule (5), and features of venous outflow obstruction (3). No cirrhosis was identified. Liver biopsies from patients on dialysis demonstrate histopathological vascular changes of INCPH. Some (31%) patients present with portal hypertension without cirrhosis. The histological changes may be reflective of underlying risk factors for INCPH in this group. © The Author(s) 2015.

Diminazene aceturate liposomes: morphometric and biochemical liver, kidney, and spleen of rats infected with Trypanosoma evansi.

PubMed

Oliveira, Camila Belmonte; Rigo, Lucas Almeida; França, Raqueli T; Gressler, Lucas T; Dalla Rosa, Luciana; Ourique, Aline F; Oliveira, Dionatan T; Doyle, Rovaina L; Moreira, Karen Luise dos Santos; Veiga, Marcelo L; Lopes, Sonia T A; Beck, Ruy Carlos R; Da Silva, Aleksandro S; Monteiro, Silvia G

2014-12-01

The aim of this study was to evaluate the effect of treatment with liposomal (L-DMZ) and conventional (C-DMZ) diminazene aceturate formulations on hepatic and renal functions of rats, experimentally infected with Trypanosoma evansi. For this purpose, 72 Wistar rats (Rattus norvegicus) were divided into six groups (A, B, C, D, E, and F). Each group was subdivided into two other subgroups in order to assess the biochemical and histological results on days 7 and 40 post-treatment (PT). Treatments were carried out based on two different therapeutic protocols: L-DMZ and C-DMZ at 3.5mg/kg(-1), single dose (groups C and D), and five successive doses within intervals of 24h (groups E and F). Groups A and B corresponded to uninfected and infected (without treatment) animals, respectively. Sample collections were held on days 7 and 40 PT for the assessment of hepatic [alkaline phosphatase (AP), alanine transferase (ALT), albumin, gamma glutamil transferase (GGT) and renal functions (creatinine and urea). Additionally, the histology of fragments of liver, kidney, and spleen was performed. Animals in group B showed a significant increase in AP, GGT, ALT, and urea when compared with group A. On day 7 post-inoculation (PI), the biochemical analysis showed a reduction (P<0.05) of AP and GGT, while the levels of urea were increased in groups C, D, E, F. On day 40 PT, ALT was increased in these same groups when compared with group A. In histopathology, changes in liver samples were observed on day 7 PT in groups D and F, especially regarding the area and density of the hepatocytes. Renal analysis exhibited changes in glomerular space, glomerular, and corpuscular areas in group E. Therefore, these results allowed us to conclude that the treatment with L-DMZ and C-DMZ led to variable biochemical changes, which defined the functions of the liver and kidneys of treated animals, since the main histopathology alterations were observed in animals treated with liposomes, at their higher dosages. Thus, treatments with L-DMZ and C-DMZ in five consecutive doses were effective although being followed by liver toxicity. Copyright © 2014 Elsevier GmbH. All rights reserved.

Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

PubMed Central

ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

2015-01-01

Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

Cholemic nephropathy - Historical notes and novel perspectives.

PubMed

Krones, Elisabeth; Pollheimer, Marion J; Rosenkranz, Alexander R; Fickert, Peter

2018-04-01

Acute kidney injury is common in patients with liver disease and associated with significant morbidity and mortality. Besides bacterial infections, fluid loss, and use of nephrotoxic drugs AKI in liver disease may be triggered by tubular toxicity of cholephiles. Cholemic nephropathy, also known as bile cast nephropathy, supposedly represents a widely underestimated but important cause of renal dysfunction in cholestasic or advanced liver diseases with jaundice. Cholemic nephropathy describes impaired renal function along with characteristic histomorphological changes consisting of intratubular cast formation and tubular epithelial cell injury directed towards distal nephron segments. The underlying pathophysiologic mechanisms are not entirely understood and clear defined diagnostic criteria are still missing. This review aims to summarize (i) the present knowledge on clinical and morphological characteristics of cholemic nephropathy, (ii) available preclinical models, (iii) potential pathomechanisms especially the potential role of bile acids, and (iv) future diagnostic and therapeutic strategies for cholemic nephropathy. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen. Copyright © 2017 Elsevier B.V. All rights reserved.

Neutrophil gelatinase‐associated lipocalin level is a prognostic factor for survival in rat and human chronic liver diseases

PubMed Central

Yoshikawa, Kyoko; Iwasa, Motoh; Kojima, Shinichi; Yoshizawa, Naohiko; Tempaku, Mina; Sugimoto, Ryosuke; Yamamoto, Norihiko; Sugimoto, Kazushi; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

2017-01-01

Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end‐stage liver disease and Child‐Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase‐associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme‐linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real‐time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll‐like receptor 4, and interleukin‐6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow‐up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946–956) PMID:29404502

γ-Benzene hexachloride poisoning leading to acute hepatorenal decompensation

PubMed Central

Paul, Rudrajit; Talukdar, Arunansu; Bhattacharya, Raja; Santra, Gouranga

2013-01-01

γ-Benzene hexachloride is a commonly used insecticide of organochlorine group. Notable toxic effects include seizures, ataxia, confusion and other central nervous system dysfunction. A 30-year-old male farmer with suicidal ingestion of γ-benzene hexachloride poison developed acute intrinsic renal failure with azotaemia and diminished urine output along with features of acute fulminate liver failure. Renal function recovered with haemodialysis and liver parameters gradually normalised with time. As per our knowledge simultaneous acute hepatic and kidney injury associated with γ-benzene hexachloride poison is never reported in humans. The exact pathophysiology of this life-threatening complication is an enigma. However, oxidative stress has been postulated as a contributory factor as suggested in animal studies. Conservative management with successful outcome in our case stresses on the impact of watchful observation and aggressive management. He was discharged after 3 weeks at stable condition and was healthy at 3 months follow-up. PMID:23925679

[A case of ruptured thoracoabdominal aortic aneurysm with aortitis syndrome--operation with selective cold visceral arteries perfusion].

PubMed

Furukawa, K; Ohteki, H; Doi, K

1997-10-01

We report a successful result of treatment for a ruptured thoracoabdominal aortic aneurysm with aortitis syndrome. A 43-year-old male suffered sudden low back pain, that was diagnosed as a ruptured thoracoabdominal aortic aneurysm based on abdominal computed tomography. Preoperative angiography revealed a thoracoabdominal aortic aneurysm with occlusion of the superior mesenteric artery, and well developed Riolan's archade. The aneurysm was replaced by a prosthetic graft with partial femoro-femoral bypass in conjunction with selective cold perfusion for the visceral arteries. Total extracorporeal circulation time, and aortic clamptime, was 187 minutes and 132 minutes, respectively. The postoperative courses of liver and renal function were excellent. The patient recovered from surgery uneventfully. It was suggested that selective cold visceral perfusion was effective for prevention of renal and liver dysfunction associated with a ruptured thoracoabdominal aneurysm.

[Leptospirosis in children of Libreville: difficult diagnosis, apropos of 1 case].

PubMed

Koko, J; Moussavou, A; Orima, C; Seilhan, C; Lemba-Abaka, A; Damas, S

2001-12-01

Leptospirosis is a widespread zoonosis, which is diagnosed less frequently in children than might be expected from the level of exposure to hazards, especially in tropical areas. A 15 1/2-year-old Gabonese boy was admitted following five days of fever, headache, myalgia, abdominal pain, diarrhea, intestinal bleeding, jaundice and conjunctival suffusion. Laboratory data showed abnormal liver and renal function tests, and diagnosis of Plasmodium falciparum malaria was confirmed by thin blood smear. The patient did not clinically improve despite antimalarial treatment and then leptospirosis was suspected. Serologic tests were performed and leptospirosis was later confirmed. Antibiotic treatment (cefuroxim) was given. The outcome was good, liver and renal tests returned to normal in a few days. In tropical area, leptospirosis should be considered in children who are diagnosed with either an unexplained fever, a pseudo-influenza syndrome, or jaundice with hepatorenal involvement and gastrointestinal bleeding.

Renal Liver-Type Fatty Acid Binding Protein (L-FABP) Attenuates Acute Kidney Injury in Aristolochic Acid Nephrotoxicity

PubMed Central

Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro

2011-01-01

Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of Nε-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of Nε-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID. PMID:21356355

Bilateral native nephrectomy to reduce oxalate stores in children at the time of combined liver-kidney transplantation for primary hyperoxaluria type 1.

PubMed

Lee, Eliza; Ramos-Gonzalez, Gabriel; Rodig, Nancy; Elisofon, Scott; Vakili, Khashayar; Kim, Heung Bae

2018-05-01

Primary hyperoxaluria type-1 (PH-1) is a rare genetic disorder in which normal hepatic metabolism of glyoxylate is disrupted resulting in diffuse oxalate deposition and end-stage renal disease (ESRD). While most centers agree that combined liver-kidney transplant (CLKT) is the appropriate treatment for PH-1, perioperative strategies for minimizing recurrent oxalate-related injury to the transplanted kidney remain unclear. We present our management of children with PH-1 and ESRD on hemodialysis (HD) who underwent CLKT at our institution from 2005 to 2015. On chart review, three patients (2 girls, 1 boy) met study criteria. Two patients received deceased-donor split-liver grafts, while one patient received a whole liver graft. All patients underwent bilateral native nephrectomy at transplant to minimize the total body oxalate load. Median preoperative serum oxalate was 72 μmol/L (range 17.8-100). All patients received HD postoperatively until predialysis serum oxalate levels fell <20 μmol/L. All patients, at a median of 7.5 years of follow-up (range 6.5-8.9), demonstrated stable liver and kidney function. While CLKT remains the definitive treatment for PH-1, bilateral native nephrectomy at the time of transplant reduces postoperative oxalate stores and may mitigate damage to the renal allograft.

Safety Measures of L-Carnitine L-Tartrate Supplementation in Healthy Men.

ERIC Educational Resources Information Center

Rubin, Martyn R.; Volek, Jeff S.; Gomez, Ana L.; Ratamess, Nicholas A.; French, Duncan N.; Sharman, Matthew J.; Kraemer, William J.

2001-01-01

Examined the effects of ingesting the dietary supplement L- CARNIPURE on liver and renal function and blood hematology among healthy men. Analysis of blood samples indicated that there were no statistically significant differences between the L-CARNIPURE and placebo conditions for any variables examined, suggesting there are no safety concerns…

Rifaximin Decreases the Incidence and Severity of Acute Kidney Injury and Hepatorenal Syndrome in Cirrhosis.

PubMed

Dong, Tien; Aronsohn, Andrew; Gautham Reddy, K; Te, Helen S

2016-12-01

While the effects of rifaximin have been shown to be protective against acute kidney injury (AKI) and hepatorenal syndrome (HRS) in alcohol-induced cirrhosis, its long-term effects on the renal function of other cirrhotic patients are unknown. To examine the long-term effects of rifaximin on the renal function of patients with cirrhosis from various etiologies. In a retrospective study, we examined cirrhotic patients at the University of Chicago Liver Clinic from January 1, 2011, to December 31, 2014. The study enrolled patients on rifaximin for ≥90 days, who were then matched by age, gender, and MELD score to a control group. Patients with malignancy and renal replacement therapy (RRT) at baseline were excluded. Data were censored at the last follow-up, termination of rifaximin therapy, initiation of RRT, death, or liver transplant. Eighty-eight rifaximin cases were identified and matched to 88 control cases. Baseline characteristics were similar, with the exceptions of more prevalent long-term midodrine use (≥90 days) (17.0 vs 4.5 %, p = 0.01) and baseline ascites (37.5 vs 23.8 %, p = 0.05) in the rifaximin group. There was no difference in the frequency of infections, deaths, liver transplants, or hospitalizations. After controlling for cofounders, the incidence rate ratio of AKI (IRR 0.71, p = 0.02) and HRS (IRR 0.21, p = 0.02), as well as the risk of requiring RRT (OR 0.23, p = 0.01), was lower in the rifaximin group. Long-term use of rifaximin is associated with a decrease incidence of AKI and HRS and a decrease risk of requiring RRT in a general population of cirrhotic patients.

First report of mesalamine (5-aminosalicylic acid) as the causative agent in a case of acute generalized exanthamous pustulosis.

PubMed

Rocci, Erin; Park, Kelly; Hutchens, Kelli; Winterfield, Laura

2017-01-15

Acute generalized exanthamous pustulosis (AGEP)is a rare eruption of non-follicular sterile pustuleson a diffuse background of erythema and edema,commonly associated with fever and leukocytosis.Antibiotics are implicated in most cases; however,other drugs have been reported to cause AGEP. Wereport a case of a 73-year-old man with a historyof ulcerative colitis who presented with a diffusepustular rash, renal failure, elevated liver functiontests, and leukocytosis with neutrophilia. A week priorto admission, the patient was started on mesalamineto treat colitis. Upon admission, a workup includinga skin biopsy was performed and was consistentwith AGEP. Mesalamine was discontinued, and thepatient's skin eruption, renal function, liver functiontests, and leukocytosis subsequently improved.Mesalamine has an unknown mechanism of action.However, it is thought to be an anti-inflammatoryagent that blocks the production of leukotrienesand prostaglandins and is an immunosuppressantthat increases the release of adenosine, whichinterferes with leukocyte function. The decrease inprostaglandin synthesis or deregulation of leukocytefunction caused by mesalamine may be the etiologyin this case. Discontinuation of the offending agentleads to resolution of AGEP, as it did in this patient.

Relationship of MTHFR gene polymorphisms with renal and cardiac disease

PubMed Central

Trovato, Francesca M; Catalano, Daniela; Ragusa, Angela; Martines, G Fabio; Pirri, Clara; Buccheri, Maria Antonietta; Di Nora, Concetta; Trovato, Guglielmo M

2015-01-01

AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism. PMID:25664255

Elevated cystatin C: is it a reflection for kidney or liver impairment in hepatic children?

PubMed

El-Sayed, Behairy; El-Araby, Hanaa; Adawy, Nermin; Hassona, Mona; El-Nady, Naglaa; Zakaria, Haidy; Khedr, Mohammed

2017-09-01

To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment ( p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) ( p < 0.0001). Cyst-C at cutoff levels of 1.65 mg/l showed 100% accuracy in discrimination between those with and those without renal impairment. Cyst-C > 2.34 mg/l predicting GFR < 40 ml/min with accuracy of 90%. Cyst-C > 2.73 mg/l predicting GFR < 20 ml/min with accuracy of 81.5%. Serum Cyst-C is a promising marker to estimate renal impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kandasamy, Neelamegam; Ashokkumar, Natarajan, E-mail: npashokkumar1@gmail.com

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine,more » blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative nephrotoxicant whether ingested or inhaled. • Myricetin enhances insulin secretion from the damaged pancreatic β-cells. • Myricetin can eliminate metals and scavenge chemical induced free radicals. • Myricetin enhances the glucose uptake by regulating insulin signaling pathway.« less

Use of Everolimus in Liver Transplantation: Recommendations From a Working Group

PubMed Central

De Simone, Paolo; Fagiuoli, Stefano; Cescon, Matteo; De Carlis, Luciano; Tisone, Giuseppe; Volpes, Riccardo; Cillo, Umberto

2017-01-01

Abstract Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mammalian target of rapamycin inhibitors have received considerable attention as immunosuppressants because they are associated with a more favorable renal profile versus CNI, as well as antiproliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking. In Italy, a project, named Everolimus: the road to long-term functioning, was initiated to collect the experience on EVR after LT with the aim of providing guidance for transplant clinicians. Herein, recommendations by this national consensus group, based on Delphi methodology, are presented. Consensus was reached on 20 of the 23 statements proposed, and their level of evidence, grade of recommendation, and percent of agreement are reported. Statements are grouped into 4 areas: (A) renal function; (B) time of EVR introduction, CNI reduction and elimination, and risk for graft rejection; (C) antiproliferative effects of EVR; and (D) management of EVR-related adverse events. The high level of consensus shows that there is good agreement on the routine use of EVR in predefined clinical scenarios, especially in light of posttransplant nephrotoxicity and other adverse events associated with long-term administration of CNIs. PMID:27495768

Early enteral feeding in postsurgical cancer patients. Fish oil structured lipid-based polymeric formula versus a standard polymeric formula.

PubMed Central

Kenler, A S; Swails, W S; Driscoll, D F; DeMichele, S J; Daley, B; Babineau, T J; Peterson, M B; Bistrian, B R

1996-01-01

OBJECTIVES: The authors compared the safety, gastrointestinal tolerance, and clinical efficacy of feeding an enteral diet containing a fish oil/medium-chain triglyceride structured lipid (FOSL-HN) versus an isonitrogenous, isocaloric formula (O-HN) in patients undergoing major abdominal surgery for upper gastrointestinal malignancies. SUMMARY BACKGROUND DATA: Previous studies suggest that feeding with n-3 fatty acids from fish oil can alter eicosanoid and cytokine production, yielding an improved immunocompetence and a reduced inflammatory response to injury. The use of n-3 fatty acids as a structured lipid can improve long-chain fatty acid absorption. METHODS: This prospective, blinded, randomized trial was conducted in 50 adult patients who were jejunally fed either FOSL-HN or O-HN for 7 days. Serum chemistries, hematology, urinalysis, gastrointestinal complications, liver and renal function, plasma and erythrocyte fatty acid analysis, urinary prostaglandins, and outcome parameters were measured at baseline and on day 7. Comparisons were made in 18 and 17 evaluable patients based a priori on the ability to reach a tube feeding rate of 40 mL/hour. RESULTS: Patients receiving FOSL-HN experienced no untoward side effects, significant incorporation of eicosapentaenoic acid into plasma and erythrocyte phospholipids, and a 50% decline in the total number of gastrointestinal complications and infections compared with patients given O-HN. The data strongly suggest improved liver and renal function during the postoperative period in the FOSL-HN group. CONCLUSION: Early enteral feeding with FOSL-HN was safe and well tolerated. Results suggest that the use of such a formula during the postoperative period may reduce the number of infections and gastrointestinal complications per patient, as well as improve renal and liver function through modulation of urinary prostaglandin levels. Additional clinical trials to fully quantify clinical benefits and optimize nutritional support with FOSL-HN should be undertaken. Images Figure 1. Figure 2. Figure 3. PMID:8604913

Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in kidney and other rat tissues.

PubMed

Khan, Sheeba; Priyamvada, Shubha; Khan, Sara A; Khan, Wasim; Farooq, Neelam; Khan, Farah; Yusufi, A N K

2009-07-01

Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.

Use of eculizumab and plasma exchange in successful combined liver-kidney transplantation in a case of atypical HUS associated with complement factor H mutation.

PubMed

Tran, Ha; Chaudhuri, Abanti; Concepcion, Waldo; Grimm, Paul C

2014-03-01

Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30-100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver-kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver-kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab. An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver-kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence. Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver-kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis.

Niacin improves renal lipid metabolism and slows progression in chronic kidney disease.

PubMed

Cho, Kyu-hyang; Kim, Hyun-ju; Kamanna, Vaijinath S; Vaziri, Nosratola D

2010-01-01

Mounting evidence points to lipid accumulation in the diseased kidney and its contribution to progression of nephropathy. We recently found heavy lipid accumulation and marked dysregulation of lipid metabolism in the remnant kidneys of rats with chronic renal failure (CRF). Present study sought to determine efficacy of niacin supplementation on renal tissue lipid metabolism in CRF. Kidney function, lipid content, and expression of molecules involved in cholesterol and fatty acid metabolism were determined in untreated CRF (5/6 nephrectomized), niacin-treated CRF (50 mg/kg/day in drinking water for 12 weeks) and control rats. CRF resulted in hypertension, proteinuria, renal tissue lipid accumulation, up-regulation of scavenger receptor A1 (SR-A1), acyl-CoA cholesterol acyltransferase-1 (ACAT1), carbohydrate-responsive element binding protein (ChREBP), fatty acid synthase (FAS), acyl-CoA carboxylase (ACC), liver X receptor (LXR), ATP binding cassette (ABC) A-1, ABCG-1, and SR-B1 and down-regulation of sterol responsive element binding protein-1 (SREBP-1), SREBP-2, HMG-CoA reductase, PPAR-alpha, fatty acid binding protein (L-FABP), and CPT1A. Niacin therapy attenuated hypertension, proteinuria, and tubulo-interstitial injury, reduced renal tissue lipids, CD36, ChREBP, LXR, ABCA-1, ABCG-1, and SR-B1 abundance and raised PPAR-alpha and L-FABP. Niacin administration improves renal tissue lipid metabolism and renal function and structure in experimental CRF.

[Severe metabolic acidosis as a result of 5-oxoproline in acetaminophen use].

PubMed

Holman, Mirjam; ter Maaten, Jan C

2010-01-01

Acetaminophen overdose is a well known cause of liver function disorder and even hepatic failure. Less well known is that even a therapeutic dose of acetaminophen may lead to life-threatening problems. We describe an 84-year-old patient with severe metabolic acidosis and an increased anion gap secondary to 5-oxoproline elevation as a result of acetaminophen use. A systematic approach can help us to determine the cause of a high anion gap metabolic acidosis. In unexplained high anion gap acidosis clinicians should consider the possibility of 5-oxoproline accumulation in patients with risk factors such as acetaminophen use, female sex, malnutrition, infection, diminished liver function or renal failure.

Living Donor Liver Transplantation for Wilson’s Disease Associated with Fulminant Hepatic Failure: A Case Report

PubMed Central

Huang, Yu; Takatsuki, Mitsuhisa; Soyama, Akihiko; Hidaka, Masaaki; Ono, Shinichiro; Adachi, Tomohiko; Hara, Takanobu; Okada, Satomi; Hamada, Takashi; Eguchi, Susumu

2018-01-01

Patient: Female, 17 Final Diagnosis: Fulminant Wilson’s disease Symptoms: General jaundice • malaise • abdominal pain Medication: — Clinical Procedure: ICU Specialty: Transplantology Objective: Rare disease Background: Liver transplantation is indicated for patients with Wilson’s disease (WD) who present either with acute liver failure or with end-stage liver disease and severe hepatic insufficiency as the first sign of disease. However, almost all reported cases have been treated with death donor liver transplantation. Here we report the case of a patient with WD associated with fulminant hepatic failure (WD-FHF) who underwent living donor liver transplantation (LDLT). Case Report: A 17-year-old female was diagnosed with WD-FHF based on high uric copper (10 603 μg/day, normal <100 μg/day), low serum ceruloplasmin (15 mg/dL, normal >20 mg/dL) and Kayser-Fleischer (K-F) corneal ring, and acute liver failure (ALF), acute renal failure (ARF) and grade 2 hepatic encephalopathy (HE). The model for end-stage liver disease (MELD) score was 35. Due to her critical condition, the patient underwent LDLT utilizing a right liver graft from her 44-year-old mother. The right hepatic vein (RHV) and inferior right hepatic vein (iRHV) were reconstructed. She developed severe liver dysfunction due to a crooked hepatic vein caused by compression from the large graft. To straighten the bend, a reoperation was performed. During the operation, we tried to relieve the compressed hepatic vein by adjusting the graft location, but the benefits were limited. We therefore performed stenting in both the RHV and iRHV on postoperative day 9. The patient gradually improved, exhibiting good liver and renal functions, and was finally discharged on postoperative day 114. Conclusions: When WD-FHF deteriorates too rapidly for conservative management, LDLT is an effective therapeutic strategy. PMID:29549236

Impact of Renal Impairment on Cardiovascular Disease Mortality After Liver Transplantation for Nonalcoholic Steatohepatitis Cirrhosis

PubMed Central

VanWagner, Lisa B.; Lapin, Brittany; Skaro, Anton I.; Lloyd-Jones, Donald M.; Rinella, Mary E.

2016-01-01

BACKGROUND & AIMS Non-alcoholic steatohepatitis (NASH) is an independent risk factor for cardiovascular disease (CVD) morbidity after liver transplantation, but its impact on CVD mortality is unknown. We sought to assess the impact of NASH on CVD mortality after liver transplantation and to predict which NASH recipients are at highest risk of a CVD-related death following a liver transplant. METHODS Using the Organ Procurement and Transplantation Network database we examined associations between NASH and post liver transplant CVD mortality, defined as primary cause of death from thromboembolism, arrhythmia, heart failure, myocardial infarction, or stroke. A physician panel reviewed cause of death. RESULTS Of 48,360 liver transplants (2/2002–12/2011), 5,057 (10.5%) were performed for NASH cirrhosis. NASH recipients were more likely to be older, female, obese, diabetic, and have history of renal failure or prior CVD versus non-NASH (p<0.001 for all). Although there was no difference in overall all-cause mortality (log-rank p=0.96), both early (30-day) and long-term CVD-specific mortality was increased among NASH recipients (Odds ratio=1.30, 95% Confidence interval (CI): 1.02–1.66; Hazard ratio=1.42, 95% CI: 1.07–1.41, respectively). These associations were no longer significant after adjustment for pre-transplant diabetes, renal impairment or CVD. A risk score comprising age ≥ 55, male sex, diabetes and renal impairment was developed for prediction of post liver transplant CVD mortality (c-statistic 0.60). CONCLUSION NASH recipients have an increased risk of CVD mortality after liver transplantation explained by a high prevalence of co-morbid cardiometabolic risk factors that in aggregate identify those at highest risk of post-transplant CVD mortality. PMID:25977117

Acute Kidney Injury after Liver Transplantation.

PubMed

Durand, François; Francoz, Claire; Asrani, Sumeet K; Khemichian, Saro; Pham, Thomas A; Sung, Randall S; Genyk, Yuri S; Nadim, Mitra K

2018-05-29

Since the implementation of the MELD score-based allocation system, the number of transplant candidates with impaired renal function has increased. The aims of this review are to present new insights in the definitions and predisposing factors that result in acute kidney injury (AKI), and to propose guidelines for the prevention and treatment of post liver transplantation (LT) AKI. This review is based on both systematic review of relevant literature and expert opinion. Pretransplant AKI is associated with posttransplant morbidity, including prolonged post LT AKI which then predisposes to posttransplant chronic kidney disease (CKD). Prevention of posttransplant AKI is essential in the improvement of long term outcomes. Accurate assessment of baseline kidney function at evaluation is necessary, taking into account that serum creatinine overestimates glomerular filtration rate (GFR). New diagnostic criteria for AKI have been integrated with traditional approaches in patients with cirrhosis to potentially identify AKI earlier and improve outcomes. Delayed introduction or complete elimination of calcineurin inhibitors during the first weeks post LT in patients with early posttransplant AKI may improve GFR in high risk patients but with higher rates of rejection and more adverse events. Biomarkers may in the future provide diagnostic information such as etiology of AKI, and prognostic information on renal recovery post-LT, and potentially impact the decision for simultaneous liver-kidney transplantation. Overall, more attention should be paid to pretransplant and early posttransplant AKI to reduce the burden of late CKD.

Some Biochemical and Hematological Parameters among Petrol Station Attendants: A Comparative Study

PubMed Central

Abou-ElWafa, Hala Samir; Albadry, Ahmed A.; Bazeed, Fagr B.

2015-01-01

Objective. To describe selected biochemical and hematological parameters (blood picture, liver enzymes, and kidney functions) in petrol station attendants in Mansoura city. Methods. This is a comparative cross-sectional study. The exposed group included 102 petrol station attendants. They were compared to a matched group of healthy 102 male service and office workers at the Faculty of Medicine, Mansoura University. The results of blood picture, liver enzymes, and kidney functions were compared between both groups. Results. Mean Red Blood Cells (RBCs) count, hemoglobin level, and Hematocrit (HCT) level were significantly lower in petrol station attendants than the comparison group. All other blood picture parameters showed nonsignificant difference between both groups. Liver enzymes, renal functions, serum albumin, and total protein showed statistically nonsignificant difference between both groups except for alanine aminotransferase (ALT) which was significantly higher in petrol station attendants. Conclusions. Some laboratory parameters among petrol station attendants showed changes that could be attributed to workplace exposure and should be given attention at preemployment and periodic medical examination. PMID:26634207

Increased Renal Clearance of Rocuronium Compensates for Chronic Loss of Bile Excretion, via upregulation of Oatp2.

PubMed

Wang, Long; Zhou, Mai-Tao; Chen, Cai-Yang; Yin, Wen; Wen, Da-Xiang; Cheung, Chi-Wai; Yang, Li-Qun; Yu, Wei-Feng

2017-01-13

Requirement for rocuronium upon surgery changes only minimally in patients with end-stage liver diseases. Our study consisted of both human and rat studies to explore the reason. The reduction rate of rocuronium infusion required to maintain neuromuscular blockade during the anhepatic phase (relative to paleohepatic phase) was examined in 16 children with congenital biliary atresia receiving orthotopic liver transplantation. Pharmacodynamics and pharmacokinetics of rocuronium were studied based on BDL rats. The role of increased Oatp2 and decrease Oatp1 expressions in renal compensation were explored. The reduction of rocuronium requirements significantly decreased in obstructively jaundiced children (24 ± 9 vs. 39 ± 11%). TOF50 in BDL rats was increased by functional removal of the kidneys but not the liver, and the percentage of rocuronium excretion through urine increased (20.3 ± 6.9 vs. 8.6 ± 1.8%), while that decreased through bile in 28d-BDL compared with control group. However, this enhanced renal secretion for rocuronium was eliminated by Oatp2 knock-down, rather than Oatp1 overexpression (28-d BDL vs. Oatp1-ShRNA or Oatp2-ShRNA, 20.3 ± 6.9 vs. 17.0 ± 6.6 or 9.3 ± 3.2%). Upon chronic/sub-chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced, by Oatp2 up-regulation.

Renal health after long-term exposure to tenofovir disoproxil fumarate (TDF) in HIV/HBV positive adults in Ghana.

PubMed

Villa, G; Phillips, R O; Smith, C; Stockdale, A J; Beloukas, A; Appiah, L T; Chadwick, D; Ruggiero, A; Sarfo, F S; Post, F; Geretti, A M

2018-06-01

The study assessed markers of renal health in HIV/HBV co-infected patients receiving TDF-containing antiretroviral therapy in Ghana. Urinary protein-to-creatinine ratio (uPCR) and albumin-to-protein ratio (uAPR) were measured cross-sectionally after a median of four years of TDF. At this time, alongside extensive laboratory testing, patients underwent evaluation of liver stiffness and blood pressure. The estimated glomerular filtration rate (eGFR) was measured longitudinally before and during TDF therapy. Among 101 participants (66% women, median age 44 years, median CD4 count 572 cells/mm 3 ) 21% and 17% had detectable HIV-1 RNA and HBV DNA, respectively. Overall 35% showed hypertension, 6% diabetes, 7% liver stiffness indicative of cirrhosis, and 18% urinary excretion of Schistosoma antigen. Tubular proteinuria occurred in 16% of patients and was independently predicted by female gender and hypertension. The eGFR declined by median 1.8 ml/min/year during TDF exposure (IQR -4.4, -0.0); more pronounced declines (≥ 5 ml/min/year) occurred in 22% of patients and were associated with receiving ritonavir-boosted lopinavir rather than efavirenz. HBV DNA, HBeAg, transaminases, and liver stiffness were not predictive of renal function abnormalities. The findings mandate improved diagnosis and management of hypertension and suggest targeted laboratory monitoring of patients receiving TDF alongside a booster in sub-Saharan Africa. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Orthotopic liver transplantation for portosystemic encephalopathy in an adult with congenital absence of the portal vein.

PubMed

Wojcicki, Maciej; Haagsma, Elizabeth B; Gouw, Annette S H; Slooff, Maarten J H; Porte, Robert J

2004-09-01

Congenital absence of the portal vein (CAPV) is a very rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. There is no portal perfusion of the liver and no portal hypertension. This abnormality is usually coincidentally discovered in children, the majority of whom have no signs of encephalopathy and only slightly abnormal liver function tests. Additional anomalies common in CAPV are cardiovascular abnormalities and hepatic tumors. To date, only 5 adult patients (>18 years) with CAPV have been described, none of whom underwent liver transplantation. We describe a 45-year-old man with CAPV and end-stage renal insufficiency due to focal segmental glomerulopathy, who developed therapy-resistant encephalopathy with intermittently high ammonia levels. The patient underwent a combined liver and kidney transplantation and is doing well at 2.5 years of follow-up. Histopathological examination of the native liver showed no portal vein branches in the portal tracts. In conclusion, our experience suggests that, although children with CAPV usually have no symptoms of encephalopathy, this may still develop at a later stage in adult life. When encephalopathy becomes refractory to medical therapy, orthotopic liver transplantation (OLT) can be successfully performed with restoration of normal cerebral function.

Left Lateral Sectionectomy of the Native Liver and Combined Living-Related Liver–Kidney Transplantation for Primary Hyperoxaluria Type 1

PubMed Central

Chen, Guo-Yong; Wei, Si-Dong; Zou, Zhong-Wu; Tang, Gao-Feng; Sun, Jian-Jun; Zhou, Shao-Tang

2015-01-01

Abstract Primary hyperoxaluria type I (PH1), the most severe form of primary hyperoxalurias, is a liver disease of the metabolic defect in glyoxylate detoxification that can be corrected by liver transplantation. A 21-year-old man presented to our center after 4 months of regular hemodialysis for kidney failure caused by nephrolithiasis. A diagnosis of PH1 was confirmed by mutations of the AGXT gene. Left lateral sectionectomy of the native liver was performed; and auxiliary partial orthotopic liver transplantation (APOLT) and kidney transplantation were carried out synchronously using a living donor. After transplantation, the patient's plasma oxalate and creatinine levels substantially decreased and the patient recovered well with good dual grafts function. APOLT and kidney transplantation can compensate the liver deficient in liver enzyme production and aid the renal elimination of oxalate, thus serving as an effective treatment option for patients with PH1. In conclusion, left lateral sectionectomy of the native liver and combined living-related liver–kidney transplantation can be a surgical option for PH1. PMID:26252291

Pre-Clinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies

PubMed Central

Waters, Alicia M.; Stewart, Jerry E.; Atigadda, Venkatram R.; Mroczek-Musulman, Elizabeth; Muccio, Donald D.; Grubbs, Clinton J.; Beierle, Elizabeth A.

2016-01-01

Rare tumors of solid organs remain some of the most difficult pediatric cancers to cure. These difficult tumors include rare pediatric renal malignancies such as malignant rhabdoid kidney tumors (MRKT) and non-osseous renal Ewing sarcoma, and hepatoblastoma, a pediatric liver tumor that arises from immature liver cells. There are data in adult renal and hepatic malignancies demonstrating the efficacy of retinoid therapy. The investigation of retinoic acid therapy in cancer is not a new strategy, but the widespread adoption of this therapy has been hindered by toxicities. Our laboratory has been investigating a novel synthetic rexinoid, UAB30, which exhibits a more favorable side effect profile. In this current study, we hypothesized that UAB30 would diminish the growth of tumor cells from both rare renal and liver tumors in vitro and in vivo. We successfully demonstrated decreased cellular proliferation, invasion and migration, cell cycle arrest and increased apoptosis after treatment with UAB30. Additionally, in in vivo murine models of human hepatoblastoma or rare human renal tumors, there were significantly decreased tumor xenograft growth and increased animal survival after UAB30 treatment. UAB30 should further be investigated as a developing therapeutic in these rare and difficult to treat, pediatric solid organ tumors. PMID:26873726

Severe leptospirosis with multiple organ failure successfully treated by plasma exchange and high-volume hemofiltration.

PubMed

Bourquin, Vincent; Ponte, Belén; Hirschel, Bernard; Pugin, Jérôme; Martin, Pierre-Yves; Saudan, Patrick

2011-01-01

Background. Leptospirosis is a spirochetal zoonosis with complex clinical features including renal and liver failure. Case report. We report the case of a Swiss fisherman presenting with leptospirosis. After initial improvement, refractory septic shock and severe liver and kidney failure developed. The expected mortality was estimated at 90% with clinical scores. The patient underwent plasma exchanges and high-volume hemofiltration (HVHF) with complete recovery of hepatic and kidney functions. Discussion. Plasma exchanges and HVHF may confer survival benefit on patients with severe leptospirosis, refractory septic shock, and multiple-organ failure.

Protective effect of Tribulus terrestris linn on liver and kidney in cadmium intoxicated rats.

PubMed

Lakshmi, G Dhana; Kumar, P Ravi; Bharavi, K; Annapurna, P; Rajendar, B; Patel, Pankaj T; Kumar, C S V Satish; Rao, G S

2012-02-01

Administration of cadmium (Cd) significantly increased the peroxidation markers such as malondialdehyde and protein carbonyls along with significant decrease in antioxidant markers such as super oxide dismutase and reduced glutathione in liver and kidney tissues. Cadmium also caused a significant alteration in hepatic and renal functional markers in serum viz. total protein, albumin, alanine transaminase, blood urea nitrogen and creatinine. Prominent pathological changes observed in liver were severe vascular and sinusoidal congestion with diffuse degenerative changes and mononuclear infiltration into peripheral areas, while the kidney showed vascular and glomerular congestion, cloudy swelling of tubular epithelium. Coadministration of ethonolic extract of T. terrestris or vitamin E along with Cd significantly reversed the Cd induced changes along with significant reduction in Cd load.

Cirrhotic cardiomyopathy

PubMed Central

Ruiz-del-Árbol, Luis; Serradilla, Regina

2015-01-01

During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function. PMID:26556983

Kidney growth and renal functions under the growth hormone replacement therapy in children.

PubMed

Ece, Aydın; Çetinkaya, Semra; Ekşioğlu, Seçil; Şenel, Saliha; Özkasap, Serdar; Giniş, Tayfur; Sen, Velat; Şahin, Cahit

2014-05-01

The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p<0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p<0.05). Height was the most significant predictor of kidney volume in rhGH received children (p<0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p<0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p>0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p<0.05). In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

Evaluation of the water disinfection by-product dichloroacetonitrile-induced biochemical, oxidative, histopathological, and mitochondrial functional alterations: Subacute oral toxicity in rats.

PubMed

Dong, Ying; Li, Fang; Shen, Haijun; Lu, Rongzhu; Yin, Siqi; Yang, Qi; Li, Zhuangfa; Wang, Suhua

2018-03-01

Dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product, is more genotoxic and cytotoxic than the currently regulated carbonaceous disinfection by-products such as haloacetic acids. Few mechanistic studies have been conducted on the hepatic and renal toxicities of DCAN. This study examined the clinical biochemical, hematological, histopathological, oxidative, and mitochondrial functional alterations to evaluate the systematic toxicity after subacute oral exposure of 11 or 44 mg/kg/day in rats for 28 days. Body and spleen weights were lower, and organ-to-body weight ratios of the liver and kidney were higher in rats administered 44-mg/kg DCAN than in controls. The activities of serum alanine aminotransferase and alkaline phosphatase, and concentrations of blood serum urea nitrogen and retinol-binding protein were increased in rats administered 44-mg/kg DCAN compared with those of controls, thereby indicating hepatic and renal damage in this group. This was confirmed by histopathological alterations, including hepatic sinus dilation, extensive hemorrhage, vacuolar degeneration in the liver and glomerulus hemorrhage, and renal tubular swelling, in DCAN-exposed rats. Exposure to 44-mg/kg DCAN induced hepatic oxidative damage shown by the significant increase in malonaldehyde levels, a poisonous product of lipid peroxidation. Exposure to 44-mg/kg DCAN significantly increased hepatic glutathione content and mitochondrial bioenergy as noted by the elevation of mitochondrial membrane potential and cytochrome c oxidase activity, which might be attributed to compensatory pathophysiologic responses to DCAN-induced hepatic mitochondrial damage.

Dengue fever in a liver-transplanted patient: a case report.

PubMed

Weerakkody, Ranga Migara; Palangasinghe, Dhammika Randula; Dalpatadu, Kaluthanthri Patabandi Chamila; Rankothkumbura, Jeewan Pradeep; Cassim, Mohammed Rezni Nizam; Karunanayake, Panduka

2014-11-21

Dengue fever is one of the commonest mosquito-borne diseases in the tropics, and Sri Lanka is no exception. Despite its commonness, dengue fever has rarely been described among patients who have undergone transplantation. We report the case of a patient with dengue fever after liver transplantation, which, to the best of our knowledge, is the first such reported case outside Brazil. Our patient was a 46-year-old Sri Lakan man who presented to our institution two years after undergoing an ABO-compatible cadaveric liver transplant. At presentation, he had typical symptoms of dengue fever. He was taking prednisolone 5mg daily and tacrolimus 3mg twice daily as immunosuppression. Initial investigations showed thrombocytopenia and neutropenia that reached a nadir by day 7 of his illness. He had elevated liver enzymes as well. The diagnosis was confirmed on the basis of NS1 antigen detection by enzyme-linked immunosorbent assay. His blood cultures and polymerase chain reaction tests for cytomegalovirus were negative. He made an uneventful recovery and was discharged by day 9 of his illness. However, normalization of liver function took nearly two weeks. In three previously reported Brazilian cases of dengue after liver transplantation, the patients presented with dengue shock syndrome, in contrast to the relatively milder presentation of our patient. Because of the lack of case reports in the literature, it is difficult to ascertain the risk factors for severe dengue infection in transplants, but dengue fever reported in renal transplants sheds some light on them. High-dose steroids increase the risk of thrombocytopenia, whereas tacrolimus has been reported to prolong the duration of symptoms. Otherwise, dengue fever is a relatively mild illness in patients who have undergone renal transplantation, and renal allograft survival has been reported to be 86% following dengue fever. Dengue is a rarely reported infection in patients who have undergone transplantation. A high degree of suspicion is required for diagnosis. Dengue NS1 antigen detection is a useful addition to the already existing methods of diagnosis. Steroids and tacrolimus have effects on the morbidity of the disease. Graft outcomes following the infection has been excellent in all reported cases.

Prospective trial of an herbal formula BYSH and Saw palmetto in patients with hormonal refractory prostate cancer: a pilot study.

PubMed

Ng, Anthony C-F; Cheng, K-F; Leung, P-C

2014-01-01

BYSH, a herbal formula, was evaluated for efficacy and safety in a pilot study for patients with advanced hormone refractory prostate cancer (HRPC). The pilot study was designed as a single-center open-label trial. Patients with HRPC were treated with BYSH for 24 weeks. The primary end point was the changes in serum prostate-specific antigen (PSA) level. Safety parameters such as liver and renal functions were monitored during the study period. Ten patients were eligible for the study. Most of them had stable PSA levels while taking BYSH. However, at the end of the BYSH treatment, the level of PSA increased. The median survival from diagnosis of HRPC was 16.4 months. Liver and renal functions remained normal. BYSH was well tolerated and no patient reported adverse events during the study period. Although it is inappropriate to make a conclusion based on the pilot study results, the trend of improvement is obvious. Further investigations should be conducted to demonstrate its clinical benefits. We have also briefly reviewed some plant products which are patented and also available in market.

Inhibition of mTOR with sirolimus does not attenuate progression of liver and kidney disease in PCK rats.

PubMed

Renken, Catharina; Fischer, Dagmar-Christiane; Kundt, Günther; Gretz, Norbert; Haffner, Dieter

2011-01-01

Activation of the mTOR pathway has been implicated in the mediation of the progression of polycystic kidney disease (PKD). Whereas targeted inhibition of mTOR has been proven to be effective in various animal models of autosomal dominant PKD, its efficacy in autosomal recessive PKD (ARPKD) remains to be elucidated. We examined the effects of sirolimus in PCK rats, an orthologous animal model of human ARPKD. Weaned PCK rats (n = 85) and SD-control rats (n = 72) received drinking water without and with sirolimus (corresponding to a daily intake of 2 mg/kg body weight) for 4, 8 and 12 weeks, respectively. The renal and hepatic functions were monitored throughout the treatment periods. Kidneys and livers were harvested and investigated with respect to progression of fibrosis, and number and size of cysts using the QWin image analysis programme. Expression of Akt, mTOR and its downstream target pS6K were assessed by immunohistochemistry. Five out of 43 sirolimus-treated PCK rats, but none of the controls, died during the study. Sirolimus treatment resulted in slightly reduced weight gain. In PCK rats, grossly enlarged kidney and livers as well as hepatic fibrosis together with enlarged bile ducts were readily detectable. Whereas activation of Akt/mTOR signalling was hardly detectable in the kidneys of SD rats, strong signals were seen in the kidneys of PCK rats. Despite a significantly reduced relative kidney weight after 12 weeks of treatment (P < 0.05), neither fibrosis and cyst area nor renal function improved during treatment. Sirolimus-treated PCK rats showed only a minor inhibition of renal mTOR-specific phosphorylation of S6K. Male PCK rats on sirolimus presented with increased concentrations of bile acids and bilirubin compared with controls (each P < 0.05 at 12 weeks). Similar, albeit non-significant, effects were noted in female PCK rats. Sirolimus failed to attenuate progression of kidney and liver disease in PCK rats. The lack of a protective effect might be due to intrinsic or acquired rapamycin resistance in this animal model of ARPKD.

[Transplant Surgeon Meets Nephrologist: Important Nephrological Aspects Before and After Kidney or Liver Transplantation].

PubMed

Vondran, F W R; Wintterle, S; Bräsen, J H; Haller, H; Klempnauer, J; Richter, N; Lehner, F; Schiffer, M

2017-04-01

In cases of chronic renal insufficiency, successful kidney transplantation is the method of choice to restore patients' health, well-being and physical fitness. The interdisciplinary collaboration of nephrologists and transplant surgeons has always been a prerequisite for the successful pre-, peri- and post-transplant care of renal transplant patients. The same holds true for liver transplant patients. Here the nephrologist is often involved in cases requiring pre- or post-transplant dialysis as well as in decision making for combined liver-kidney transplantation. This review focuses on nephrological aspects in patient care before and after kidney and liver transplantation. Georg Thieme Verlag KG Stuttgart · New York.

Simultaneous Liver-Kidney Transplantation: Impact on Liver Transplant Patients and the Kidney Transplant Waiting List.

PubMed

Miles, Clifford D; Westphal, Scott; Liapakis, AnnMarie; Formica, Richard

2018-01-01

The number of simultaneous liver-kidney transplants (SLKT) performed in the USA has been rising. The Organ Procurement and Transplantation Network implemented a new policy governing SLKT that specifies eligibility criteria for candidates to receive a kidney with a liver, and creates a kidney waitlist "safety net" for liver recipients with persistent renal failure after transplant. This review explores potential impacts for liver patients and the kidney waitlist. Factors that have contributed to the rise in SLKT including Model for End-stage Liver Disease (MELD)-based allocation, regional sharing for high MELD candidates, and the rising incidence of non-alcoholic steatohepatitis will continue to increase the number of liver transplant candidates with concurrent renal insufficiency. The effect of center behavior based on the new policy is harder to predict, given wide historic variability in SLKT practice. Continued increase in combined liver/kidney failure is likely, and SLKT and kidney after liver transplant may both increase. Impact of the new policy should be carefully monitored, but influences beyond the policy need to be accounted for.

Sequential use of hemoperfusion and single-pass albumin dialysis can safely reverse methotrexate nephrotoxicity.

PubMed

Chan, Winnie Kwai Yu; Hui, Wun Fung

2016-10-01

High-dose methotrexate therapy (HDMTX) is a common form of chemotherapy used in children with high-grade malignancy such as osteosarcoma. Treatment with HDMTX requires careful monitoring of drug levels with folinic acid (leucovorin) rescue therapy. Toxicity from methotrexate is not uncommon and sometimes causes significant morbidity and mortality. We report an 11-year-old child whose 24-h post-HDMTX serum level was 651.8 μmol/L (recommended level <20 μmol/L), which was complicated by septic shock and progressive renal and liver failure. As carboxypeptidase (glucarpidase) was not available locally, she was treated with the sequential use of charcoal hemoperfusion (CHP) and single-pass albumin dialysis (SPAD). The patient recovered without complications. Both liver and renal function recovered with no significant late sequelae. CHP and SPAD are effective extracorporeal methods of removing methotrexate. They provide alternative treatment options for critical care nephrologists in the management of methotrexate toxicity.

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected inmore » the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.« less

Protective effect of Malva sylvestris L. extract in ischemia-reperfusion induced acute kidney and remote liver injury

PubMed Central

Najafi, Houshang; Mohamadi Yarijani, Zeynab; Changizi-Ashtiyani, Saeed; Mansouri, Kamran; Modarresi, Masoud; Madani, Seyed Hamid

2017-01-01

Mallow (Malva sylvestris L.) has had medicinal and therapeutic uses in addition to its oral consumption. The present study was conducted to examine the protective effect of Malva sylvestris L. extract on ischemia-reperfusion-induced kidney injury and remote organ injuries in the liver. Before ischemia-reperfusion, rats in the different groups received intraperitoneal normal saline or mallow extract at the doses of 200, 400 or 600 mg/kg of body weight. After 30-minutes of bilateral renal ischemia followed by 24-hours of reperfusion, tissue damage in the kidney and liver samples were determined through studying H&E-stained slides under a light microscope. The degree of leukocyte infiltration and tissue mRNA expressions of TNF- and ICAM-1 were then measured to examine the degree of renal inflammation. The renal tissue MDA and FRAP levels were measured for determining the amount of oxidative stress. Plasma concentrations of creatinine, urea, ALT and ALP were also measured. Ischemia-reperfusion led to a significant increase in plasma concentrations of creatinine, urea, ALT and ALP, and renal tissue MDA, and a significant decrease in renal tissue FRAP. The expression of pro-inflammatory factors in the kidney tissue, the level of leukocyte infiltration and the amount of tissue damage in the kidney and liver also increased. Pretreatment by mallow extract led to a significant improvement in all the variables measured. The 200- and 400-mg doses yielded better results in most parameters compared to the 600-mg dose. The findings showed that mallow extract protects the kidney against ischemia-reperfusion and reduces remote organ injury in the liver. PMID:29155898

High-Fat Diet Increased Renal and Hepatic Oxidative Stress Induced by Vanadium of Wistar Rat.

PubMed

Wang, J P; Cui, R Y; Zhang, K Y; Ding, X M; Luo, Y H; Bai, S P; Zeng, Q F; Xuan, Y; Su, Z W

2016-04-01

The study was conducted to assess the effect of vanadium (V) in high-fat diet on the liver and kidney of rats in a 5-week trial. Seventy-two female Wistar rats (BW = 95 ± 5 g) were randomly allotted into eight groups. Groups I, II, III, and IV obtained low-fat diet containing 0, 3, 15, and 30 mg/kg V, and V, VI, VII, and VIII groups received the respective vanadium doses with high-fat diet, respectively. There were lesions in the liver and kidney of V, VI, VII, and VIII groups, granular degeneration and vacuolar degeneration were observed in the renal tubular and glomerulus epithelial cells, and hepatocytes showed granular degeneration and vacuolar degeneration. Supplemented high-fat diet with vanadium was shown to decrease (P < 0.05) activities of superoxide dismutase, total antioxidant capacity, glutathione-S transferase, and NAD(P)H/quinone oxidoreductase 1 (NQO1) and increase malondialdehyde content in the liver and kidney. The relative expression of hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) and NQO1 mRNA was downregulated by V addition and high-fat diet, and the effect of V was more pronounced in high-fat diet (interaction, P < 0.05), with VIII group having the lowest mRNA expression of Nrf-2 and NQO1 in the liver and kidney. In conclusion, it suggested that dietary vanadium ranging from 15 to 30 mg/kg could lead to oxidative damage and vanadium accumulation in the liver and kidney, which caused renal and hepatic toxicity. The high-fat diet enhanced vanadium-induced hepatic and renal damage, and the mechanism was related to the modulation of the hepatic and renal mRNA expression of Nrf-2 and NQO1.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marques da Silva, A; Narciso, L

Purpose: Commercial workstations usually have their own software to calculate dynamic renal functions. However, usually they have low flexibility and subjectivity on delimiting kidney and background areas. The aim of this paper is to present a public domain software, called RenalQuant, capable to semi-automatically draw regions of interest on dynamic renal scintigraphies, extracting data and generating renal function quantification parameters. Methods: The software was developed in Java and written as an ImageJ-based plugin. The preprocessing and segmentation steps include the user’s selection of one time frame with higher activity in kidney’s region, compared with background, and low activity in themore » liver. Next, the chosen time frame is smoothed using a Gaussian low pass spatial filter (σ = 3) for noise reduction and better delimitation of kidneys. The maximum entropy thresholding method is used for segmentation. A background area is automatically placed below each kidney, and the user confirms if these regions are correctly segmented and positioned. Quantitative data are extracted and each renogram and relative renal function (RRF) value is calculated and displayed. Results: RenalQuant plugin was validated using retrospective 20 patients’ 99mTc-DTPA exams, and compared with results produced by commercial workstation software, referred as reference. The renograms intraclass correlation coefficients (ICC) were calculated and false-negative and false-positive RRF values were analyzed. The results showed that ICC values between RenalQuant plugin and reference software for both kidneys’ renograms were higher than 0.75, showing excellent reliability. Conclusion: Our results indicated RenalQuant plugin can be trustingly used to generate renograms, using DICOM dynamic renal scintigraphy exams as input. It is user friendly and user’s interaction occurs at a minimum level. Further studies have to investigate how to increase RRF accuracy and explore how to solve limitations in the segmentation step, mainly when background region has higher activity compared to kidneys. Financial support by CAPES.« less

Regional traumatic limb hypothermia attenuates distant hepatic and renal injury following blast limb trauma in rats.

PubMed

Zhao, Hongzhi; Ning, Jiaolin; Duan, Jiaxiang; Gu, Jianteng; Yi, Bin; Lu, Kaizhi; Mo, Liwen; Lai, Xinan; Hennah, Lindsay; Ma, Daqing

2014-09-01

Blast limb injury was reported to result in distant organ injury including the lungs, which can be attenuated with transient regional hypothermia (RH) to the injured limb. We aimed to further study hepatic and renal injuries following blast limb trauma and also to evaluate the protective effects of regional traumatic limb hypothermia on such injuries in rats. Blast limb trauma (BLT) was created using chartaceous electricity detonators in anesthetized male Sprague-Dawley rats. The BLT rats were randomly allocated to undergo regional traumatic limb hypothermic treatment (RH) for 30 minutes, 60 minutes, or 6 hours immediately after the onset of blast or without RH (n = 8 per group). The severity of hepatic and renal injury was assessed through histologic examination and water content (wet/dry weight) in all animals 6 hours later. The level of plasma tumor necrosis factor α (TNF-α), interleukin 6, hydrogen sulfide (H2S), and myeloperoxidase (MPO) together with hepatic and renal MPO, malondialdehyde (MDA), superoxide dismutase, and total antioxidant capacity were measured 6 hours after the blast injury. Following BLT, hepatic injury was evidenced by histopathologic changes, increased water content, as well as plasma alanine aminotransferase and aspartate aminotransferase. Renal histopathologic but not functional changes were also found. RH treatment for all durations attenuated this distant renal injury, but only RH treatment for 60 minutes and 6 hours attenuated distant hepatic injury following BLT. RH treatment for all durations decreased plasma TNF-α and interleukin 6, reduced liver and kidney MPO activity and kidney MDA, and elevated superoxide dismutase and total antioxidant capacity in both liver and kidneys. RH treatment for 60 minutes is the most effective duration to reduce hepatic MPO activity, plasma TNF-α, and kidney MDA. This study indicates that BLT-induced distant renal and hepatic injury could be attenuated by RH treatment through reduction of cytokine release and inhibition of neutrophil accumulation and oxidative stress.

Acute spinal cord injury changes the disposition of some, but not all drugs given intravenously.

PubMed

García-López, P; Martínez-Cruz, A; Guízar-Sahagún, G; Castañeda-Hernández, G

2007-09-01

Experimental laboratory investigations in paraplegic rats. In order to understand why acute spinal cord injury (SCI) changes the disposition of some, but not all drugs given intravenously (i.v.), pharmacokinetic parameters of drugs with different pharmacological properties were evaluated to determine the influence of SCI on physiological processes such as distribution, metabolism and excretion. Mexico City, Mexico. Rats were subjected to severe SCI (contusion) at T-9 level; pharmacokinetic studies of phenacetin, naproxen or gentamicin were performed 24 h after. These drugs were not chosen as markers because of their therapeutic properties, but because of their pharmacokinetic characteristics. Additional studies including plasma proteins, liver and renal function tests, and micro-vascular hepatic blood flow, were also performed at the same time after injury. Acute SCI significantly reduced distribution of drugs with intermediate and low binding to plasma proteins (phenacetin 30% and gentamicin 10%, respectively), but distribution did not change when naproxen - a drug highly bound to plasma proteins (99%) - was used, in absence of changes in plasma proteins. Metabolism was significantly altered only for a drug with liver blood flow - limited clearance (phenacetin) and not for a drug with liver capacity-limited clearance (naproxen). The liver function test did not change, whereas the hepatic micro-vascular blood flow significantly decreased after SCI. Renal excretion, evaluated by gentamicin clearance, was significantly reduced as a consequence of SCI, without significant changes in serum creatinine. Changes in drug disposition associated to acute SCI are complex and generalization is not possible. They are highly dependent on each drug properties as well as on the altered physiological processes. Results motivate the quest for strategies to improve disposition of selective i.v. drugs during spinal shock, in an effort to avoid therapeutic failure.

Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

PubMed Central

Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

2016-01-01

Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

Chemical Composition of Golden Berry Leaves Against Hepato-renal Fibrosis.

PubMed

Khalaf-Allah, Abd El-Rahman M; El-Gengaihi, Souad E; Hamed, Manal A; Zahran, Hanan G; Mohammed, Mona A

2016-01-01

The role of Physalis peruviana (golden berry) as functional food against hepato-renal fibrosis induced by carbon tetrachloride (CCl4) was evaluated. The chemical composition of leaves referred the presence of withanolides and flavonoids. Two compounds, ursolic acid and lupeol, were isolated and their structures were elucidated by different spectral analysis techniques. The biological evaluation was conducted on different animal groups; control rats, control orally treated with plant extract (500 mg/kg body weight twice a week for six consecutive weeks), CCl4 (0.5 ml/kg body weight diluted to 1:9 (v/v) in olive oil and injected intraperitoneally) group, CCl4 treated with plant extract and CCl4 treated with silymarin as a reference herbal drug. The evaluation was done through measuring oxidative stress markers; malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO). Liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea and serum protein were also evaluated. The results revealed plant safety and decrease in NO, MDA, IgG, ALP, tissue protein, bilirubin, creatinine and urea levels. Increase in SOD, AST, ALT, GGT and serum protein levels were observed. Improvement in liver and kidney histopathological architectures were also seen. In conclusion, Physalis peruviana recorded a significant protective role in liver and kidney against fibrosis. Further studies are needed to evaluate its isolated compounds and its use in pharmacological applications and clinical uses.

The Impact of Hospital/Surgeon Volume on Acute Renal Failure and Mortality in Liver Transplantation: A Nationwide Cohort Study.

PubMed

Cheng, Chih-Wen; Liu, Fu-Chao; Lin, Jr-Rung; Tsai, Yung-Fong; Chen, Hsiu-Pin; Yu, Huang-Ping

2016-01-01

The aim of this study was to assess whether the case volume of surgeons and hospitals affects the rates of postoperative complications and survival after liver transplantation. This population-based retrospective cohort study included 2938 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. They were divided into two groups, according to the cumulative case volume of their operating surgeons and the case volume of their hospitals. The duration of intensive care unit stay and post-transplantation hospitalization, postoperative complications, and mortality were analyzed. The results showed that, in the low and high case volume surgeons groups, respectively, acute renal failure occurred at the rate of 14.11% and 5.86% (p<0.0001), and the overall mortality rates were 19.61% and 12.44% (p<0.0001). In the low and high case volume hospital groups, respectively, acute renal failure occurred in 11% and 7.11% of the recipients (p = 0.0004), and the overall mortality was 18.44% and 12.86% (p<0.0001). These findings suggest that liver transplantation recipients operated on higher case volume surgeons or in higher case volume hospitals have a lower rate of acute renal failure and mortality.

Assessment of Added Value of Noncontrast to Contrast-Enhanced Abdominal Computed Tomography Scan for Characterization of Hypervascular Liver Metastases☆

PubMed Central

Sadigh, Gelareh; Nandwana, Sadhna B.; Moreno, Courtney; Cox, Kelly L.; Baumgarten, Deborah A.; Switchenko, Jeffrey; Easter, Tiffany; Applegate, Kimberly E.

2017-01-01

Assess the added value of nonenhanced computed tomography (NECT) to contrast-enhanced CT (CECT) of the abdomen for characterization of hypervascular liver metastases and incidental findings. Institutional review board approved, Health Insurance Probability and Accountability Act compliant, retrospective study of patients with melanoma, neuroendocrine tumor, or thyroid cancer. First available triphasic abdomen CT after initial diagnosis was reviewed by 3 radiologists. The 3 most suspicious lesions were characterized on the CECT as benign or malignant and then recharacterized after reviewing the NECT with CECT. Incidental renal and adrenal lesions were characterized similarly. Diagnostic performance of CECT vs its combination with NECT was assessed. Statistical significance level was set at P < 0.05. A total of 81 patients were included (mean age = 55 years; 52% male; 64% with liver lesions; 27% and 11% with incidental renal and adrenal lesions, respectively). Percentage area under the curve and 95% CI of CECT vs combination with NECT for characterization of liver metastases was 98(94–100) vs 99(96–100) for reviewer 1 (P = 0.35), 93(86–100) vs 94(87–100) for reviewer 2 (P = 0.23), and 96(90–100) vs 99(97–100) for reviewer 3 (P = 0.32). Mean difference in area under the curve and 95% CI between 2 protocols for characterization of liver, renal, and adrenal lesions were −0.007(−0.05 to 0.04) (P = 0.63), −0.09(−0.25 to 0.07) (P = 0.22), and −0.01(−0.05 to 0.02) (P = 0.27), respectively. After addition of NECT, confidence level for lesion characterization increased 4%–15% for liver metastases, 18%–59% and 33%–67% for renal and adrenal lesions, respectively. In conclusion, while addition of NECT to CECT improved radiologist' confidence, there was no statistically significant change in characterization of hypervascular liver metastases or incidental renal and adrenal lesions. PMID:27397022

[Pathophysiology of heat illness].

PubMed

Aruga, Tohru; Miyake, Yasufumi

2012-06-01

Human core temperature is strictly controlled by mechanism of radiation, conduction, convection, and evaporation from skin surface. Serial hot and humid climate induces dehydration which interferes heat pump-out from the body. Heart dysfunction is the third factor to rise body temperature. Hyperthermia and hypo-perfusion caused by dehydration and heart failure deteriorate specific organ functions, i.e. central nervous system, liver and renal functions and coagulation system. Disseminated intravascular coagulopathy is one of the standard indicators of severity and mortality of heat stroke.

Long-term intermittent glutamine supplementation repairs intestinal damage (structure and functional mass) with advanced age: assessment with plasma citrulline in a rodent model.

PubMed

Beaufrère, A M; Neveux, N; Patureau Mirand, P; Buffière, C; Marceau, G; Sapin, V; Cynober, L; Meydinal-Denis, D

2014-11-01

Glutamine is the preferred fuel for the rat small intestine and promotes the growth of intestinal mucosa, especially in the event of gut injury. Quantitatively, glutamine is one important precursor for intestinal citrulline release. The aim of this study was to determine whether the effect of glutamine on the increase in intestinal villus height is correlated with an increase in both gut mass and citrulline plasma level in very old rats. We intermittently supplemented very old (27-mo) female rats with oral glutamine (20% of diet protein). Intestinal histomorphometric analysis of the small bowel was performed. Amino acids, in particular citrulline, were measured in the plasma, liver and jejunum. Markers of renal (creatinine, urea) and liver (alanine aminotransferase [ALT]) and aspartate aminotransferase (AST) functions were measured to evaluate renal and liver functions in relation to aging and to glutamine supplementation. Liver glutathione was also determined to evaluate cellular redox state. Glutamine supplementation maintains the body weight of very old rats, not by limiting sarcopenia but rather by increasing the organ mass of the splanchnic area. Total intestine mass was significantly higher in glutamine-supplemented rats than in controls (15%). Measurement of villus height and crypt depth demonstrated that the difference between villus and crypt was significantly improved in glutamine pre-treated rats compared to controls (~ 11%). Plasma citrulline also increased by 15% in glutamine-supplemented rats compared to controls. Citrulline appears as a biomarker of enterocyte mass in villous atrophy associated with advanced age. Non-invasive measurement of this metabolite may be useful in following the state of the gastrointestinal tract in very old people, whose numbers are increasing worldwide and the care of whom is a major public health issue. The gut may contribute to the malnutrition caused by malabsorption frequently observed in the elderly.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus.

PubMed

Li, Jiang; Guo, Qing-Jun; Cai, Jin-Zhen; Pan, Cheng; Shen, Zhong-Yang; Jiang, Wen-Tao

2017-12-07

Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Liver transplantation: Current status and challenges

PubMed Central

Jadlowiec, Caroline C; Taner, Timucin

2016-01-01

Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function. PMID:27182155

[Intestinal absorption of Ca47 in chronic renal insufficiency before and after treatment with 1,25 dihydroxycholecalciferol].

PubMed

Vattimo, A

1979-12-01

The effects of vitamin D3 follow its metabolisation in the liver and then in the kidney. Its most active metabolite is 1,25 (OH)2D3, produced by the liver precursor 25(OH)D3. In chronic renal insufficiency, demineralising osteopathy can be corrected by administering 1,25 (OH)2D3 to make up for its under-production by the kidneys. An assessment if is made of 47Ca intestinal transport in patients with chronic renal insufficiency before and after such treatment. It was found that the effects of the metabolite on calcium transport were dose-dependent.

Liver and kidney toxicity induced by Afzal smokeless tobacco product in Oman.

PubMed

Al-Mukhaini, Nawal; Ba-Omar, Taher; Eltayeb, Elsadig; Al-Shihi, Aisha; Al-Riyami, Nafila; Al-Belushi, Jamila; Al-Adawi, Kawthar

2017-04-01

Afzal, the common smokeless tobacco product (STP) in Oman, is believed to contain toxins that may impair the function of some organs such as liver and kidney. An aqueous extract from Afzal was added to drinking water to be administrated orally to Wistar albino rats (n=72) young and adult from both genders weighing between 60-80g and 150-240g respectively for 8 weeks. Animals were divided into three groups: control (distilled water instead of Afzal extract), low-dose (3mgnicotine/kgbodyweight/day) and high-dose (6mgnicotine/kgbodyweight/day). The animals were euthanized and their blood, liver and kidney were collected for biochemical and histopathological investigations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed for the liver function, while blood urea nitrogen (BUN) and creatinine (CRT) were assayed for the kidney function. The results showed a significant increase in the ALT, AST, BUN and CRT levels (P<0.05) in both Afzal-treated groups (low and high doses) compared with the control. Histopathological findings revealed the initial but seem to be serious degenerative alterations of periportal fibrosis in liver and edematous and calcified changes in renal glomerulus among Afzal-treated groups. Additionally, the weight gain of the Afzal-treated groups was lower than the control group. Our findings show that the exposure of Wistar rats to the Afzal extract has the potentials of causing decreased weight gain and dose-dependent functional and structural damage to the biochemical and histological profiles of liver and kidney as well as serious biochemical effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metastatic Neuroendocrine Tumour in a Renal Transplant Recipient: Dual-Tracer PET-CT with (18)F-FDG and (68)Ga-DOTANOC in This Rare Setting.

PubMed

Karunanithi, Sellam; Roy, Shambo Guha; Sharma, Punit; Yadav, Rajni; Bal, Chandrasekhar; Kumar, Rakesh

2015-03-01

Recipients of renal transplant are at increased risk of developing various malignancies, especially post-transplant lymphoproliferative disorder (PTLD) and skin cancers. Neuroendocrine tumours (NET) of the gastrointestinal tract have not been reported in this setting. Here we describe the case of a 75-year-old male who had undergone renal transplant 8 years back and now presented with significant weight loss and backache, clinically suspected as PTLD. (18)F-Fluordeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) showed hypermetabolic lesions in the liver and rectum, raising the suspicion of PTLD. However, biopsy from the liver lesion showed poorly differentiated NET. (68)Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI(3)-octreotide ((68)Ga-DOTANOC) PET-CT was then done, which confirmed the primary lesion in the rectum with liver metastases.

Renal tubular function in children with tyrosinaemia type I treated with nitisinone.

PubMed

Santra, S; Preece, M A; Hulton, S-A; McKiernan, P J

2008-06-01

Tyrosinaemia type I (TTI) is an inherited deficiency in the enzyme fumarylacetoacetate hydrolase and is frequently complicated by renal tubular dysfunction which may persist in some patients after hepatic transplantation. Nitisinone has revolutionized the management of TTI but its effect on renal tubular dysfunction has not been described in a large cohort of patients. To document the incidence and progression of renal tubular dysfunction in children with TTI treated with nitisinone at a single centre. Twenty-one patients with TTI from a single centre were treated with nitisinone for at least 12 months. Median age at first treatment was 17 weeks (range 1 week to 27 months). Nine patients (43%) presented in acute liver failure, seven (33%) had a chronic presentation and five (24%) were detected pre-clinically. A retrospective case analysis of plasma phosphate, urinary protein/creatinine ratio and tubular reabsorption of phosphate was performed for all patients as markers of tubular function. Renal ultrasounds were examined for evidence of nephrocalcinosis and where available, skeletal radiographs for rickets. All patients had biochemical evidence of renal tubular dysfunction at presentation. After nitisinone and dietary treatment were started, all three markers normalized within one year. Four children had clinical rickets at presentation (which improved), of whom one had nephrocalcinosis, which did not reverse on nitisinone. No child redeveloped tubular dysfunction after commencing nitisinone. All patients with TTI had evidence of tubular dysfunction at presentation and in all cases this resolved with nitisinone and dietary control. The tubulopathy associated with TTI is reversible.

Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review.

PubMed

Clericetti, Caterina M; Milani, Gregorio P; Lava, Sebastiano A G; Bianchetti, Mario G; Simonetti, Giacomo D; Giannini, Olivier

2018-03-01

Hyperammonemia usually results from an inborn error of metabolism or from an advanced liver disease. Individual case reports suggest that both distal renal tubular acidosis and urinary tract infection may also result in hyperammonemia. A systematic review of the literature on hyperammonemia secondary to distal renal tubular acidosis and urinary tract infection was conducted. We identified 39 reports on distal renal tubular acidosis or urinary tract infections in association with hyperammonemia published between 1980 and 2017. Hyperammonemia was detected in 13 children with distal renal tubular acidosis and in one adult patient with distal renal tubular acidosis secondary to primary hyperparathyroidism. In these patients a negative relationship was observed between circulating ammonia and bicarbonate levels (P < 0.05). In 31 patients (19 children, 12 adults), an acute urinary tract infection was complicated by acute hyperammonemia and symptoms and signs of acute neuronal dysfunction, such as an altered level of consciousness, convulsions and asterixis, often associated with signs of brain edema, such as anorexia and vomiting. Urea-splitting bacteria were isolated in 28 of the 31 cases. The urinary tract was anatomically or functionally abnormal in 30 of these patients. This study reveals that both altered distal renal tubular acidification and urinary tract infection may be associated with relevant hyperammonemia in both children and adults.

High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation.

PubMed

Kitada, Kento; Daub, Steffen; Zhang, Yahua; Klein, Janet D; Nakano, Daisuke; Pedchenko, Tetyana; Lantier, Louise; LaRocque, Lauren M; Marton, Adriana; Neubert, Patrick; Schröder, Agnes; Rakova, Natalia; Jantsch, Jonathan; Dikalova, Anna E; Dikalov, Sergey I; Harrison, David G; Müller, Dominik N; Nishiyama, Akira; Rauh, Manfred; Harris, Raymond C; Luft, Friedrich C; Wassermann, David H; Sands, Jeff M; Titze, Jens

2017-05-01

Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter-driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.

High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation

PubMed Central

Kitada, Kento; Daub, Steffen; Zhang, Yahua; Klein, Janet D.; Nakano, Daisuke; Pedchenko, Tetyana; Lantier, Louise; LaRocque, Lauren M.; Marton, Adriana; Neubert, Patrick; Schröder, Agnes; Rakova, Natalia; Jantsch, Jonathan; Dikalova, Anna E.; Dikalov, Sergey I.; Harrison, David G.; Müller, Dominik N.; Nishiyama, Akira; Rauh, Manfred; Harris, Raymond C.; Luft, Friedrich C.; Wasserman, David H.; Sands, Jeff M.

2017-01-01

Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter–driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions. PMID:28414295

Ciprofloxacin and statin interaction: a cautionary tale of rhabdomyolysis.

PubMed

Goldie, Fraser Charles; Brogan, Amy; Boyle, James Graham

2016-07-28

A 62-year-old woman presented to hospital, on general practitioner (GP) advice, with a 15-day history of slowly progressing muscle weakness. Results showed newly deranged liver function and creatine kinase (CK) of >24 000. Prior medical history includes previous myocardial infarction and recurrent urinary tract infection. 4 days prior to symptom onset, the patient developed typical urinary tract infection symptoms, treated with ciprofloxacin. The patient had been taking simvastatin (40 mg nocte) for 13 years and had never previously taken ciprofloxacin. Initial management included intravenous crystalloid fluids and discontinuation of simvastatin. CK level fell, liver function slowly improved and renal function remained stable. Muscle weakness improved and the patient became independently able to perform activities of daily living. While the interactions between statins and other antibiotics are well documented, the interaction between statins and ciprofloxacin is less so. The consequences of this interaction can have potentially serious outcomes. 2016 BMJ Publishing Group Ltd.

Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction.

PubMed

Sho, Takuya; Suda, Goki; Nagasaka, Atsushi; Yamamoto, Yoshiya; Furuya, Ken; Kumagai, Kenichi; Uebayashi, Minoru; Terashita, Katsumi; Kobayashi, Tomoe; Tsunematsu, Izumi; Onodera, Manabu; Meguro, Takashi; Kimura, Megumi; Ito, Jun; Umemura, Machiko; Izumi, Takaaki; Kawagishi, Naoki; Ohara, Masatsugu; Ono, Yuji; Nakai, Masato; Natsuizaka, Mitsuteru; Morikawa, Kenichi; Ogawa, Koji; Sakamoto, Naoya

2018-06-01

The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)-infected patients with renal dysfunction. The study included genotype 2 HCV-infected patients who received SOF and RBV between July 2014 and May 2017. The sustained virologic response (SVR) after the treatment and safety during the therapy were evaluated according to renal function. A total of 231 patients were included in this study. The median age was 62 years old, and 45.9% (106/231) were men. Of the 231 patients, 191 (82.8%) and 40 (17.2%) were classified as having chronic kidney disease (CKD) stages G1/2 and G3, respectively. The overall SVR rate was 97% (224/231). The SVR rates in patients with CKD stages G1, 2, G3a, and G3b were 98.1%, 98.6%, 87.9%, and 100%, respectively, and this therapy was tolerated. Multivariate analysis indicated that renal dysfunction was significantly associated with a non-SVR (odds ratio, 6.963; 95% confidence interval, 1.494-32.41; P = 0.013). The patients with renal dysfunction were older, had advanced liver fibrosis, lower baseline platelet and hemoglobin levels, and a higher rate of RBV dose reduction. Sofosbuvir and RBV therapy is highly effective and safe for genotype 2 HCV-infected Japanese patients. However, attention should be paid to baseline renal function when SOF- and RBV-containing regimens are used for patients with renal dysfunction. © 2018 The Japan Society of Hepatology.

Transjugular intrahepatic portosystemic shunt: impact on systemic hemodynamics and renal and cardiac function in patients with cirrhosis.

PubMed

Busk, Troels M; Bendtsen, Flemming; Poulsen, Jørgen H; Clemmesen, Jens O; Larsen, Fin S; Goetze, Jens P; Iversen, Jens S; Jensen, Magnus T; Møgelvang, Rasmus; Pedersen, Erling B; Bech, Jesper N; Møller, Søren

2018-02-01

Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension and possibly increases central blood volume (CBV). Moreover, renal function often improves; however, its effects on cardiac function are unclear. The aims of our study were to examine the effects of TIPS on hemodynamics and renal and cardiac function in patients with cirrhosis. In 25 cirrhotic patients, we analyzed systemic, cardiac, and splanchnic hemodynamics by catheterization of the liver veins and right heart chambers before and 1 wk after TIPS. Additionally, we measured renal and cardiac markers and performed advanced echocardiography before, 1 wk after, and 4 mo after TIPS. CBV increased significantly after TIPS (+4.6%, P < 0.05). Cardiac output (CO) increased (+15.3%, P < 0.005) due to an increase in stroke volume (SV) (+11.1%, P < 0.005), whereas heart rate (HR) was initially unchanged. Cardiopulmonary pressures increased after TIPS, whereas copeptin, a marker of vasopressin, decreased (-18%, P < 0.005) and proatrial natriuretic peptide increased (+52%, P < 0.0005) 1 wk after TIPS and returned to baseline 4 mo after TIPS. Plasma neutrophil gelatinase-associated lipocalin, renin, aldosterone, and serum creatinine decreased after TIPS (-36%, P < 0.005; -65%, P < 0.05; -90%, P < 0.005; and -13%, P < 0.005, respectively). Echocardiography revealed subtle changes in cardiac function after TIPS, although these were within the normal range. TIPS increases CBV by increasing CO and SV, whereas HR is initially unaltered. These results indicate an inability to increase the heart rate in response to a hemodynamic challenge that only partially increases CBV after TIPS. These changes, however, are sufficient for improving renal function. NEW & NOTEWORTHY For the first time, we have combined advanced techniques to study the integrated effects of transjugular intrahepatic portosystemic shunt (TIPS) in cirrhosis. We showed that TIPS increases central blood volume (CBV) through improved cardiac inotropy. Advanced echocardiography demonstrated that myocardial function was unaffected by the dramatic increase in preload after TIPS. Finally, renal function improved due to the increase in CBV. Recognition of these physiological changes significantly contributes to our clinical understanding of TIPS.

Houttuynia cordata extract increased systemic exposure and liver concentrations of metformin through OCTs and MATEs in rats.

PubMed

You, Byoung Hoon; Chin, Young-Won; Kim, Hojun; Choi, Han Seok; Choi, Young Hee

2018-06-01

The synergistic activity of Houttuynia cordata ethanol extract (HCT) and metformin combination in diabetic rats has been previously reported, but the fundamental causes remain unsolved. Organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) transport metformin to the liver and kidneys. Therefore, pharmacological activity and systemic exposure of metformin in HCT-metformin combination were determined from pharmacokinetic change and glucose-lowering activity using in vitro HEK-293 cells expressing human OCTs or human MATEs and in vivo rats. HCT inhibited human OCT2 and human MATE1-mediated metformin transports in vitro. In in vivo rats, treatment with HCT and metformin for 28 days in rats (28MH rats) reduced the rat Oct2-mediated renal excretion of metformin and thereby the increased systemic exposure of metformin compared with only metformin-treated rats for 28 days (28M rats). In 28MH rats, rat Oct1-mediated metformin uptake into the liver was enhanced, leading to an improved glucose-lowering effect without hypoglycaemia compared with 28M rats. There was no impairment of renal function in HCT and metformin treatments. These results suggest that HCT-metformin combination therapy is applicable in terms of efficacy and safety. Copyright © 2018 John Wiley & Sons, Ltd.

Prevalence and Clinical Manifestations of Malaria in Aligarh, India

PubMed Central

Asma, Umm-e; Taufiq, Farha

2014-01-01

Malaria is one of the most widespread infectious diseases of tropical countries with an estimated 207 million cases globally. In India, there are endemic pockets of this disease, including Aligarh. Hundreds of Plasmodium falciparum and P. vivax cases with severe pathological conditions are recorded every year in this district. The aim of this study is to find out changes in liver enzymes and kidney markers. Specific diagnosis for P. falciparum and P. vivax was made by microscopic examination of Giemsa stained slides. Clinical symptoms were observed in both of these infections. Liver enzymes, such as AST, ALT, and ALP, and kidney function markers, such as creatinine and urea, were estimated by standard biochemical techniques. In Aligarh district, P. vivax, P. falciparum, and mixed infections were 64%, 34%, and 2%, respectively. In case of P. falciparum infection, the incidences of anemia, splenomegaly, renal failure, jaundice, and neurological sequelae were higher compared to those in P. vivax infection. Recrudescence and relapse rates were 18% and 20% in P. falciparum and P. vivax infections, respectively. Liver dysfunctions and renal failures were more common in P. falciparum patients, particularly in elderly patients. Artesunate derivatives must, therefore, be introduced for the treatment of P. falciparum as they resist to chloroquine as well as sulfadoxine-pyrimethamine combinations. PMID:25548413

Prevalence and clinical manifestations of malaria in Aligarh, India.

PubMed

Asma, Umm-e; Taufiq, Farha; Khan, Wajihullah

2014-12-01

Malaria is one of the most widespread infectious diseases of tropical countries with an estimated 207 million cases globally. In India, there are endemic pockets of this disease, including Aligarh. Hundreds of Plasmodium falciparum and P. vivax cases with severe pathological conditions are recorded every year in this district. The aim of this study is to find out changes in liver enzymes and kidney markers. Specific diagnosis for P. falciparum and P. vivax was made by microscopic examination of Giemsa stained slides. Clinical symptoms were observed in both of these infections. Liver enzymes, such as AST, ALT, and ALP, and kidney function markers, such as creatinine and urea, were estimated by standard biochemical techniques. In Aligarh district, P. vivax, P. falciparum, and mixed infections were 64%, 34%, and 2%, respectively. In case of P. falciparum infection, the incidences of anemia, splenomegaly, renal failure, jaundice, and neurological sequelae were higher compared to those in P. vivax infection. Recrudescence and relapse rates were 18% and 20% in P. falciparum and P. vivax infections, respectively. Liver dysfunctions and renal failures were more common in P. falciparum patients, particularly in elderly patients. Artesunate derivatives must, therefore, be introduced for the treatment of P. falciparum as they resist to chloroquine as well as sulfadoxine-pyrimethamine combinations.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

PubMed

Anty, R; Favre, G; Coilly, A; Rossignol, E; Houssel-Debry, P; Duvoux, C; De Ledinghen, V; Di Martino, V; Leroy, V; Radenne, S; Kamar, N; Canva, V; D'Alteroche, L; Durand, F; Dumortier, J; Lebray, P; Besch, C; Tran, A; Canivet, C M; Botta-Fridlund, D; Montialoux, H; Moreno, C; Conti, F; Silvain, C; Perré, P; Habersetzer, F; Abergel, A; Debette-Gratien, M; Dharancy, S; Esnault, V L M; Fougerou-Leurent, C; Cagnot, C; Diallo, A; Veislinger, A; Danjou, H; Samuel, D; Pageaux, G-P; Duclos-Vallée, J-C

2018-06-01

In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m 2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m 2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients. © 2018 John Wiley & Sons Ltd.

Donation after cardiac death liver transplantation is associated with increased risk of end-stage renal disease.

PubMed

Ruebner, Rebecca L; Reese, Peter P; Abt, Peter L

2014-12-01

Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end-stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty-three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow-up of 3.93 years, ESRD occurred in 2008 (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P = 0.06; DRI ≥1.40 and <1.72: HR 1.29, P = 0.003; DRI ≥1.72: HR 1.39, P < 0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long-term renal outcomes in liver transplant recipients. © 2014 Steunstichting ESOT.

Quantitative Features of Liver Lesions, Lung Nodules, and Renal Stones at Multi-Detector Row CT Examinations: Dependency on Radiation Dose and Reconstruction Algorithm.

PubMed

Solomon, Justin; Mileto, Achille; Nelson, Rendon C; Roy Choudhury, Kingshuk; Samei, Ehsan

2016-04-01

To determine if radiation dose and reconstruction algorithm affect the computer-based extraction and analysis of quantitative imaging features in lung nodules, liver lesions, and renal stones at multi-detector row computed tomography (CT). Retrospective analysis of data from a prospective, multicenter, HIPAA-compliant, institutional review board-approved clinical trial was performed by extracting 23 quantitative imaging features (size, shape, attenuation, edge sharpness, pixel value distribution, and texture) of lesions on multi-detector row CT images of 20 adult patients (14 men, six women; mean age, 63 years; range, 38-72 years) referred for known or suspected focal liver lesions, lung nodules, or kidney stones. Data were acquired between September 2011 and April 2012. All multi-detector row CT scans were performed at two different radiation dose levels; images were reconstructed with filtered back projection, adaptive statistical iterative reconstruction, and model-based iterative reconstruction (MBIR) algorithms. A linear mixed-effects model was used to assess the effect of radiation dose and reconstruction algorithm on extracted features. Among the 23 imaging features assessed, radiation dose had a significant effect on five, three, and four of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). Adaptive statistical iterative reconstruction had a significant effect on three, one, and one of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). MBIR reconstruction had a significant effect on nine, 11, and 15 of the features for liver lesions, lung nodules, and renal stones, respectively (P < .002 for all comparisons). Of note, the measured size of lung nodules and renal stones with MBIR was significantly different than those for the other two algorithms (P < .002 for all comparisons). Although lesion texture was significantly affected by the reconstruction algorithm used (average of 3.33 features affected by MBIR throughout lesion types; P < .002, for all comparisons), no significant effect of the radiation dose setting was observed for all but one of the texture features (P = .002-.998). Radiation dose settings and reconstruction algorithms affect the extraction and analysis of quantitative imaging features in lesions at multi-detector row CT.

Chronic Kidney Disease and Related Long-term Complications Following Liver Transplantation

PubMed Central

Sharma, Pratima; Bari, Khurram

2015-01-01

Liver transplantation (LT) is the standard of care for patients with decompensated cirrhosis. LT recipients have excellent short-term and long-term outcomes including patient and graft survival. Since the adoption of model for end-stage liver disease (MELD) - based allocation policy, the incidence of post-transplant end stage renal disease has risen significantly. Occurrence of stage 4 chronic kidney disease and end stage renal disease substantially increase the risk of post-transplant deaths. Since majority of late post-transplant mortality is due to non-hepatic post-transplant comorbidities, personalized care directed towards risk factor modification may further improve post-transplant survival. PMID:26311603

Pharmacological inhibition of Src kinase protects against acute kidney injury in a murine model of renal ischemia/reperfusion

PubMed Central

Zhou, Xiaoxu; Liu, Lirong; Masucci, Monica V.; Tang, Jinhua; Li, Xuezhu; Liu, Na; Bayliss, George; Zhao, Ting C.; Zhuang, Shougang

2017-01-01

Activation of Src kinase has been implicated in the pathogenesis of acute brain, liver, and lung injury. However, the role of Src in acute kidney injury (AKI) remains unestablished. To address this, we evaluated the effects of Src inhibition on renal dysfunction and pathological changes in a murine model of AKI induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in increased Src phosphorylation at tyrosine 416 (activation). Administration of PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved renal function and ameliorated renal pathological damage. PP1 treatment also suppressed renal expression of neutrophil gelatinase-associated lipocalin and reduced apoptosis in the injured kidney. Moreover, Src inhibition prevented downregulation of several adherens and tight junction proteins, including E-cadherin, ZO-1, and claudins-1/−4 in the kidney after I/R injury as well as in cultured renal proximal tubular cells following oxidative stress. Finally, PP1 inhibited I/R–induced renal expression of matrix metalloproteinase-2 and -9, phosphorylation of extracellular signal–regulated kinases1/2, signal transducer and activator of transcription-3, and nuclear factor-κB, and the infiltration of macrophages into the kidney. These data indicate that Src is a pivotal mediator of renal epithelial injury and that its inhibition may have a therapeutic potential to treat AKI. PMID:28415724

Ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius).

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-12-01

This study describes the ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius). Images of the liver were obtained from the 11th to 5th intercostal spaces (ICSs). The distance between the dorsal liver margin and the midline of the back was shortest (39.1 ± 7.4 cm) at the 11th ICS and increased cranially to 5th ICS. The size of the liver was largest at the 9th ICS and smallest at the 5th ICS. In 6 camels the right kidney was visualized from the 10th and 11th ICSs and upper right flank and in the 10th and 11th ICSs in the remaining 16 camels. In all camels, the left kidney was imaged from the caudal left flank. In 21 camels, the differentiation between the renal cortex and medulla was clearly visible in the ultrasonograms. Ultrasonographic description of the liver and kidneys provides a basic reference for diagnosing hepatic and renal disorders in camels.

Ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius)

PubMed Central

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-01-01

This study describes the ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius). Images of the liver were obtained from the 11th to 5th intercostal spaces (ICSs). The distance between the dorsal liver margin and the midline of the back was shortest (39.1 ± 7.4 cm) at the 11th ICS and increased cranially to 5th ICS. The size of the liver was largest at the 9th ICS and smallest at the 5th ICS. In 6 camels the right kidney was visualized from the 10th and 11th ICSs and upper right flank and in the 10th and 11th ICSs in the remaining 16 camels. In all camels, the left kidney was imaged from the caudal left flank. In 21 camels, the differentiation between the renal cortex and medulla was clearly visible in the ultrasonograms. Ultrasonographic description of the liver and kidneys provides a basic reference for diagnosing hepatic and renal disorders in camels. PMID:23729824

Kidney, Pancreas and Liver Allocation and Distribution in the United States

PubMed Central

Smith, J. M.; Biggins, S. W.; Haselby, D. G.; Kim, W. R.; Wedd, J.; Lamb, K.; Thompson, B.; Segev, D. L.; Gustafson, S.; Kandaswamy, R.; Stock, P. G.; Matas, A. J.; Samana, C. J.; Sleeman, E. F.; Stewart, D.; Harper, A.; Edwards, E.; Snyder, J. J.; Kasiske, B. L.; Israni, A. K.

2013-01-01

Kidney transplant and liver transplant are the treatments of choice for patients with end-stage renal disease and end-stage liver disease, respectively. Pancreas transplant is most commonly performed along with kidney transplant in diabetic end-stage renal disease patients. Despite a steady increase in the numbers of kidney and liver transplants performed each year in the United States, a significant shortage of kidneys and livers available for transplant remains. Organ allocation is the process the Organ Procurement and Transplantation Network (OPTN) uses to determine which candidates are offered which deceased donor organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation. The policy has changed incrementally over time in efforts to optimize allocation to meet these often competing goals. This review describes the history, current status and future direction of policies regarding the allocation of abdominal organs for transplant, namely the kidney, liver and pancreas, in the United States. PMID:23157207

A norovirus outbreak triggered by copper intoxication on a coach trip from the Netherlands to Germany, April 2010.

PubMed

Hoefnagel, J; van de Weerdt, Dh; Schaefer, O; Koene, R

2012-03-01

We report an unusual outbreak of norovirus infection on a coach trip. Overall, 30 of 40 people (including drivers and crew) developed nausea, vomiting and/or diarrhoea, 11 of them on the first day of the trip. The incidence epidemic curve showed a first peak on Day 1 and a second on Day 4. Nine passengers were hospitalised with gastrointestinal symptoms. Norovirus was found in stool samples from two patients, but the infection could not explain the first peak in the epidemic curve only a few hours after departure. Interviews with the passengers and an inspection of the coach and its water supply implicated the water used for coffee and tea as the potential source. Microbiological investigations of the water were negative, but chemical analysis showed a toxic concentration of copper. Blood copper levels as well as renal and liver function were determined in 28 of the 32 passengers who had been exposed to the water. One passenger who did not have gastrointestinal symptoms had an elevated copper level of 25.9 μmol/L, without loss of liver or renal function. It is likely that the spread of norovirus was enhanced because of vomiting of one of the passengers due to copper intoxication.

[Liver transplantation preserving the vena cava and a temporary portocaval shunt].

PubMed

Hesse, U J; Berrevoet, F; Troisi, R; Mortier, E; Decruyenaere, J; Pattyn, P; de Hemptinne, B

1999-02-01

The experience with laterolateral cavocavostomy for hepatovenous reconstruction in liver transplantation is reviewed with and without the use of a temporary portocaval shunt. A total of 65 liver transplantations were analyzed. In 49 transplantations a laterolateral cavocaval anastomosis was performed (group I). In group II (n = 16) the same technique was used after a temporary portal caval shunt was constructed. Mean arterial pressure (mmHg): group I 128 +/- 34; group II 109 +/- 32. Cardiac output (l/min) decrease during the anhepatic phase was 2.3 +/- 1.9 and 1.2 +/- 1.5, respectively (P < 0.05). The peroperative blood loss measured as the number of packed cells transfused was 16.4 +/- 15.8 versus 1.2 +/- 2.3 (P < 0.04) and fresh frozen plasma 19.0 +/- 14.7 versus 3.7 +/- 4.0 (P < 0.02). Course on ICU (days), liver function tests, renal function and the need for reoperation because of bleeding were not statistically significantly different between the groups. One-year patient survival was 82.7 and 85.7%, respectively. In conclusion, we found that despite preservation of the caval flow during hepatectomy, the additional use of a temporary portocaval shunt was advantageous with regard to peroperative hemorrhage and hemodynamic stability and can potentially facilitate implantation of the liver graft.

[Contraception and pregnancy after liver transplantation: an update overview].

PubMed

Parolin, Mônica Beatriz; Coelho, Júlio Cezar Uili; Urbanetz, Almir Antônio; Pampuch, Melina

2009-01-01

Successful liver transplantation not only treats the underlying liver disease but also restores libido and fertility in female recipients. Although reports of successful pregnancy after liver transplantation continue to increase, these pregnancies are considered of high-risk because they are associated with increase maternofetal morbidity. A MEDLINE search (1978-2007) was conducted using the terms 'liver transplantation', 'pregnancy', 'immunosuppressive agents', 'sexual function'. Reviews, retrospective series, long-term clinical follow-up of case series and original articles containing basic scientific observations were included. Although no formal guidelines have been established there are some 'golden rules' to improve the probability of favorable maternal and fetal outcome. Most transplant centers recommend to delay pregnancy for at least 1-year after transplantation. The recipient should be on a stable immunosuppression regimen, with good graft function and no evidence of renal dysfunction or uncontrolled arterial hypertension. Considering the increased incidence of prematurity, low birth weight, hypertension and preeclampsia reported during pregnancy post-LT, these high-risk patients should be managed by a multidisciplinary team, including an obstetrician specialized in high-risk pregnancies. Carefully monitoring of immunosuppressive drugs serum level is prudent to avoid graft rejection episodes and drugs with teratogenic potential should be discontinued. Breastfeeding is usually not recommended. Successful pregnancies are the rule after liver transplantation. A carefully monitoring by an experience multidisciplinary team increases the chances of favorable maternofetal outcome.

Systemic effect of mineral aggregate-based cements: histopathological analysis in rats.

PubMed

Garcia, Lucas da Fonseca Roberti; Huck, Claudia; Magalhães, Fernando Augusto Cintra; Souza, Pedro Paulo Chaves de; Souza Costa, Carlos Alberto de

2017-01-01

Several studies reported the local tissue reaction caused by mineral aggregate-based cements. However, few studies have investigated the systemic effects promoted by these cements on liver and kidney when directly applied to connective tissue. The purpose of this in vivo study was to investigate the systemic effect of mineral aggregate-based cements on the livers and kidneys of rats. Samples of Mineral Trioxide Aggregate (MTA) and a calcium aluminate-based cement (EndoBinder) containing different radiopacifiers were implanted into the dorsum of 40 rats. After 7 and 30 d, samples of subcutaneous, liver and kidney tissues were submitted to histopathological analysis. A score (0-3) was used to grade the inflammatory reaction. Blood samples were collected to evaluate changes in hepatic and renal functions of animals. The moderate inflammatory reaction (2) observed for 7 d in the subcutaneous tissue decreased with time for all cements. The thickness of inflammatory capsules also presented a significant decrease with time (P<.05). Systemically, all cements caused adverse inflammatory reactions in the liver and kidney, being more evident for MTA, persisting until the end of the analysis. Liver functions increased significantly for MTA during 30 d (P<.05). The different cements induced to a locally limited inflammatory reaction. However, from the systemic point of view, the cements promoted significant inflammatory reactions in the liver and kidney. For MTA, the reactions were more accentuated.

Donor-transmitted, donor-derived, and de novo cancer after liver transplant.

PubMed

Chapman, Jeremy R; Lynch, Stephen V

2014-03-01

Cancer is the third most common cause of death (after cardiovascular disease and infection) for patients who have a functioning kidney allograft. Kidney and liver transplant recipients have similar cancer risks because of immunosuppression but different risks because of differences in primary diseases that cause renal and hepatic failure and the inherent behavior of cancers in the liver. There are 4 types of cancer that may develop in liver allograft recipients: (1) recurrent cancer, (2) donor-transmitted cancer, (3) donor-derived cancer, and (4) de novo cancer. Identification of potential donor cancer transmission may occur at postmortem examination of a deceased donor or when a probable donor-transmitted cancer is identified in another recipient. Donor-transmitted cancer after liver transplant is rare in Australia, the United Kingdom, and the United States. Aging of the donor pool may increase the risk of subclinical cancer in donors. Liver transplant recipients have a greater risk of de novo cancer than the general population, and risk factors for de novo cancer in liver transplant recipients include primary sclerosing cholangitis, alcoholic liver disease, smoking, and increased age. Liver transplant recipients may benefit from cancer screening because they have a high risk, are clearly identifiable, and are under continuous medical supervision.

Steato-Score: Non-Invasive Quantitative Assessment of Liver Fat by Ultrasound Imaging.

PubMed

Di Lascio, Nicole; Avigo, Cinzia; Salvati, Antonio; Martini, Nicola; Ragucci, Monica; Monti, Serena; Prinster, Anna; Chiappino, Dante; Mancini, Marcello; D'Elia, Domenico; Ghiadoni, Lorenzo; Bonino, Ferruccio; Brunetto, Maurizia R; Faita, Francesco

2018-05-04

Non-alcoholic fatty liver disease is becoming a global epidemic. The aim of this study was to develop a system for assessing liver fat content based on ultrasound images. Magnetic resonance spectroscopy measurements were obtained in 61 patients and the controlled attenuation parameter in 54. Ultrasound images were acquired for all 115 participants and used to calculate the hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization. The Steato-score was obtained by combining these five parameters. Magnetic resonance spectroscopy measurements were significantly correlated with hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization; Steato-score was dependent on hepatic/renal ratio, attenuation rate and diaphragm visualization. Area under the receiver operating characteristic curve was equal to 0.98, with 89% sensitivity and 94% specificity. Controlled attenuation parameter values were significantly correlated with hepatic/renal ratio, attenuation rate, diaphragm visualization and Steato-score; the area under the curve was 0.79. This system could be a valid alternative as a non-invasive, simple and inexpensive assessment of intrahepatic fat. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation.

PubMed

Ip, Stephen; Hussaini, Trana; Daulat, Aliya; Partovi, Nilufar; Erb, Siegfried R; Yoshida, Eric M; Marquez, Vladimir

2017-01-01

Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. To examine the risk factors in the development of CRF in these patients. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

Multi organ assessment of Compensated Cirrhosis Patients using quantitative Magnetic Resonance Imaging.

PubMed

Bradley, Christopher R; Cox, Eleanor F; Scott, Robert A; James, Martin W; Kaye, Phillip; Aithal, Guruprasad P; Francis, Susan T; Guha, Indra Neil

2018-06-07

Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs in a single scan has implications for determining the balance of benefit versus harm for therapies. Our aim was to establish the feasibility of Magnetic Resonance Imaging to assess changes in compensated cirrhosis (CC), and relate this to disease severity and future liver related outcomes (LROs). 60 CC patients, 40 healthy volunteers and 7 decompensated cirrhotics were recruited. In a single scan session, MRI measures comprised phase-contrast MRI vessel blood flow, arterial spin labelling tissue perfusion, T 1 longitudinal relaxation time and volume assessment of liver, spleen and kidneys, heart rate and cardiac index. We explore MRI parameters with disease severity and differences in baseline MRI parameters in those 11 (18%) of CC patients who had future LROs. In the liver compositional changes were reflected by increased T 1 in progressive disease (p<0.001) and an increase in liver volume in CC (p=0.006), with associated progressive reduction in liver (p < 0.001) and splenic (p<0.001) perfusion. A significant reduction in renal cortex T 1 and increase in cardiac index and superior mesenteric arterial (SMA) blood flow was seen with increasing disease severity. Baseline liver T 1 (p=0.01) and perfusion (p< 0.01), and renal cortex T 1 (p<0.01) were significantly different in CC patients who subsequently developed negative LROs. MRI allows the contemporaneous assessment of organs in liver cirrhosis in a single scan without the requirement of contrast agent. MRI parameters of liver T 1, renal T 1, hepatic and splenic perfusion, and SMA blood flow were related to risk of LROs. This study assesses the changes to structure, blood flow and perfusion that occur in the key organs (liver, spleen and kidney) associated with severe liver disease (compensated cirrhosis). Those MRI measures which change with disease severity and are related to negative liver related clinical outcomes are described. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

SIMULTANEOUS LIVER KIDNEY TRANSPLANTATION IN LIVER TRANSPLANT CANDIDATES WITH RENAL DYSFUNCTION: IMPORTANCE OF CREATININE LEVELS, DIALYSIS, AND ORGAN QUALITY IN SURVIVAL

PubMed Central

Tanriover, Bekir; MacConmara, Malcolm P.; Parekh, Justin; Arce, Cristina; Zhang, Song; Gao, Ang; Mufti, Arjmand; Levea, Swee-Ling; Sandikci, Burhaneddin; Ayvaci, Mehmet U.S.; Ariyamuthu, Venketash K.; Hwang, Christine; Mohan, Sumit; Mete, Mutlu; Vazquez, Miguel A.; Marrero, Jorge A.

2016-01-01

Background The survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK transplant survival has not been well described in the literature. Methods The Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N=2,700) or SLK (N=1,361) transplantation with moderate renal insufficiency between 2003 and 2013. The study cohort was stratified into four groups based on serum creatinine (Scr< 2 mg/dL versus Scr≥ 2 mg/dL) and dialysis status at listing and at transplant. The patients with end-stage renal disease and requiring acute dialysis more than three months before transplantation were excluded. A propensity score (PS)-matching was performed in each stratified groups to factor out imbalances between the SLK and LTA regarding covariates distribution and to reduce measured confounding. Donor quality was assessed with liver-donor risk index (L-DRI). The primary outcome of interest was post-transplant mortality. Results On multivariable PS-matched Cox proportional hazard models, SLK led to decrease in post-transplant mortality compared to LTA across all four groups, but only reached statistical significance (HR 0.77; 95% CI, 0.62–0.96) in the recipients not exposed to dialysis and Scr≥ 2 mg/dL at transplant (mortality incidence rate per patient-year 5.7% in SLK vs. 7.6% in LTA, p=0.005). The decrease in mortality was observed among SLK recipients with better quality donors (L-DRI<1.5). Conclusions Exposure to pre-transplantation dialysis and donor quality affected overall survival among SLK recipients. PMID:27942610

Acute presentation of gestational diabetes insipidus with pre-eclampsia complicated by cerebral vasoconstriction: a case report and review of the published work.

PubMed

Mor, Amir; Fuchs, Yael; Zafra, Kathleen; Haberman, Shoshana; Tal, Reshef

2015-08-01

Gestational diabetes insipidus (GDI) is a rare, self-limited complication of pregnancy. As it is related to excess placental vasopressinase enzyme activity, which is metabolized in the liver, GDI is more common in pregnancies complicated by conditions associated with liver dysfunction. We present a case of a 41-year-old woman at 38 weeks' gestation who presented with pre-eclampsia with severe features, including impaired liver function and renal insufficiency. Following cesarean section she was diagnosed with GDI, which was further complicated by cerebral vasoconstriction as demonstrated by magnetic resonance angiography. This case raises the possibility that cerebral vasoconstriction may be related to the cause of GDI. A high index of suspicion of GDI should be maintained in patients who present with typical signs and symptoms, especially in the setting of pregnancy complications associated with liver dysfunction. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Temporary metabolic support by extracorporeal blood therapy for liver failure after surgery.

PubMed

Matsubara, S; Okabe, K; Ouchi, K; Sato, T; Matsuno, S

1988-01-01

With the aim of temporarily assisting deterioration of liver function developing after surgery, extracorporeal blood purification therapy (EBPT) (plasma exchange and/or hemofiltration) was carried out in 26 postoperative patients. Initiation of EBPT was instituted according to the criteria of either a serum bilirubin greater than 15 mg/dl or Grade 2 or more coma. Plasma exchange was carried out 235 times in 23 patients and hemofiltration was performed 28 times for seven patients. In addition, hemodialysis and CAPD were linked in eight cases. Plasma exchange was found to control the progression of DIC and endotoxemia. Nine patients (35%) were weaned from EBPT. In the survivors the levels of blood ammonia and number of major complications were significantly lower compared to the nonsurvivors. Three patients treated only with hemofiltration were all lost. Among co-morbid factors present, incidences of renal failure, respiratory failure, and associated liver cirrhosis significantly increased poor clinical outcome on EBPT for postoperative liver failure.

Renal cell metastases versus liver hemangioma.

PubMed

Mydlo, J H; Shore, N; Herr, H W

1991-03-01

We present the case of a man with presumed metastatic renal cell carcinoma based on radiologic examination and weight loss, who refused treatment of any kind for one year. A surgical exploration to control hematuria revealed a Stage I tumor.

Cockcroft-Gault revisited: New de-liver-ance on recommendations for use in cirrhosis.

PubMed

Scappaticci, Gianni B; Regal, Randolph E

2017-01-28

The Cockcroft-Gault (CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine (SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the "rounding up" approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance (CrCl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure CrCl. Furthermore, "rounding up" of SCr values often underestimated CrCl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

Renal Involvement in Inflammatory Bowel Diseases.

PubMed

Corica, Domenico; Romano, Claudio

2016-02-01

The prevalence of extraintestinal manifestations in inflammatory bowel diseases varies from 6% to 46%. The aetiology of extraintestinal manifestations remains unclear. There are theories based on an immunological response influenced by genetic factors. Extraintestinal manifestations can involve almost every organ system. They may originate from the same pathophysiological mechanism of intestinal disease, or as secondary complications of inflammatory bowel diseases, or autoimmune diseases susceptibility. The most frequently involved organs are the joints, skin, eyes, liver and biliary tract. Renal involvement has been considered as an extraintestinal manifestation and has been described in both Crohn's disease and ulcerative colitis. The most frequent renal involvements in patients with inflammatory bowel disease are nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis. The aim of this review is to evaluate and report the most important data in the literature on renal involvement in patients with inflammatory bowel disease. Bibliographical searches were performed of the MEDLINE electronic database from January 1998 to January 2015 with the following key words (all fields): (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND (kidney OR renal OR nephrotoxicity OR renal function OR kidney disease OR renal disease OR glomerulonephritis OR interstitial nephritis OR amyloidosis OR kidney failure OR renal failure) AND (5-aminosalicylic acid OR aminosalicylate OR mesalazine OR TNF-α inhibitors OR cyclosporine OR azathioprine OR drugs OR pediatric). Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Neutrophil Gelatinase Associated Lipocalin (NGAL) - a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof?

PubMed

Firu, S G; Streba, C T; Firu, D; Tache, D E; Rogoveanu, I

2015-01-01

Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. We have searched through current literature and analyzed all significant full text articles on this topic. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed.

Pyogenic Liver Abscess as Endemic Disease, Taiwan

PubMed Central

Tsai, Feng-Chiao; Huang, Yu-Tsung; Chang, Luan-Yin

2008-01-01

Pyogenic liver abscess has become a health problem in Taiwanese society. However, the extent of this problem has remained unclear because of the lack of a population-based study. We therefore performed a nationwide analysis of pyogenic liver abscess in Taiwan from 1996 through 2004. We analyzed 29,703 cases from the Taiwan National Health Insurance database and 506 cases from National Taiwan University Hospital. Our analysis showed that the annual incidence of pyogenic liver abscess increased steadily from 11.15/100,000 population in 1996 to 17.59/100,000 in 2004. Diabetes, malignancy, renal disease, and pneumonia were associated with a higher risk for the disease. By contrast, death due to pyogenic liver abscess decreased over time, although population-based abscess-related death increased slightly. Renal disease, malignancy, pneumonia, and heart disease correlated with higher death rates; Klebsiella pneumoniae infection and therapeutic procedures were related to lower death rates. Diabetes did not significantly change death rates for the 506 patients from the hospital. PMID:18826824

The in vivo effects of adenine-induced chronic kidney disease on some renal and hepatic function and CYP450 metabolizing enzymes.

PubMed

Al Za'abi, M; Shalaby, A; Manoj, P; Ali, B H

2017-05-04

Adenine-induced model of chronic kidney disease (CKD) is a widely used model especially in studies testing novel nephroprotective agents. We investigated the effects of adenine-induced CKD in rats on the activities of some xenobiotic metabolizing enzymes in liver and kidneys, and on some in vivo indicators of drug metabolism (viz pentobarbitone sleeping time, and plasma concentration of theophylline 90 min post administration). CKD was induced by orally feeding adenine (0.25 % w/w) for 35 days. Adenine induced all the characteristics of CKD, which was confirmed by biochemical and histological findings. Glutathione concentration and activities of some enzymes involved in its metabolism were reduced in kidneys and livers of rats with CKD. Renal CYP450 1A1 activity was significantly inhibited by adenine, but other measured isoenzymes (1A2, 3A4 and 2E1) were not significantly affected. Adenine significantly prolonged pentobarbitone-sleeping time and increased plasma theophylline concentration 90 min post administration. Adenine also induced a moderate degree of hepatic damages as indicated histologically and by significant elevations in some plasma enzymes. The results suggest that adenine-induced CKD is associated with significant in vivo inhibitory activities on some drug-metabolizing enzymes, with most of the effect on the kidneys rather than the liver.

Liquid chromatography-mass spectrometry-based metabolomics and lipidomics reveal toxicological mechanisms of bisphenol F in breast cancer xenografts.

PubMed

Zhao, Chao; Xie, Peisi; Wang, Hailin; Cai, Zongwei

2018-05-05

Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts. Our results demonstrated that BPF exposure disturbed the metabolome and lipidome of liver and kidney. Exposure induced reprogramming of the glutathione (GSH) biosynthesis and glycolytic metabolism by activating glycine, serine, cysteine, glutamine, lactate and pyruvate in liver and kidney tissues. It also perturbed the biosynthesis and degradation of glycerophospholipids (GPs) and glycerolipids (GLs), resulting in abnormality of membrane homeostasis and cellular functions in kidney tissues. Moreover, spatial distribution and profile of metabolites changed across renal cortex and medulla regions after BPF treatment. Levels of phosphatidylethanolamines (PE) and triacylglycerols (TAG) increased in renal medulla and pelvis, while the levels of phosphatidylcholines (PC) and phosphatidylinositols (PI) increased in cortex and pelvis. These observations offer a deeper understanding of critical role of metabolites and lipid reprogramming in BPF-induced biological effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Characteristics and Management of Blunt Renal Injury in Children

PubMed Central

Ishida, Yuichi; Tyroch, Alan H.; Emami, Nader; McLean, Susan F.

2017-01-01

Background: Renal trauma in the pediatric population is predominately due to blunt mechanism of injury. Our purpose was to determine the associated injuries, features, incidence, management, and outcomes of kidney injuries resulting from blunt trauma in the pediatric population in a single level I trauma center. Methods: This was a retrospective chart and trauma registry review of all pediatric blunt renal injuries at a regional level I trauma center that provides care to injured adults and children. The inclusion dates were January 2001–June 2014. Results: Of 5790 pediatric blunt trauma admissions, 68 children sustained renal trauma (incidence: 1.2%). Only two had nephrectomies (2.9%). Five renal angiograms were performed, only one required angioembolization. Macroscopic hematuria rate was significantly higher in the high-grade injury group (47% vs. 16%; P = 0.031). Over half of the patients had other intra-abdominal injuries. The liver and spleen were the most frequently injured abdominal organs. Conclusion: Blunt renal trauma is uncommon in children and is typically of low American Association for the Surgery of Trauma injury grade. It is commonly associated with other intra-abdominal injuries, especially the liver and the spleen. The nephrectomy rate in pediatric trauma is lower compared to adult trauma. Most pediatric blunt renal injury can be managed conservatively by adult trauma surgeons. PMID:28855777

The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting.

PubMed

Rademaker, Marius; Gupta, Monisha; Andrews, Megan; Armour, Katherine; Baker, Chris; Foley, Peter; Gebauer, Kurt; George, Jacob; Rubel, Diana; Sullivan, John

2017-08-01

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low-dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti-inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non-fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at-risk groups include an HIV test, a QuantiFERON-TB Gold test and a chest X-ray. In patients without complications, repeat the FBC at 2-4 weeks, then every 3-6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low-dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment-emergent liver toxicity is related to underlying metabolic syndrome and non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: '20 mg/day' has been corrected to '20 gm/day'.] Although MTX is a potential teratogen post-conception, there is little evidence for this pre-conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri-surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti-tumour necrosis factor biologics. © 2016 The Australasian College of Dermatologists.

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease.

PubMed

Targher, Giovanni; Byrne, Christopher D

2017-05-01

Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.

Water-soluble C60 fullerenes reduce manifestations of acute cholangitis in rats

NASA Astrophysics Data System (ADS)

Kuznietsova, H. M.; Lynchak, O. V.; Dziubenko, N. V.; Osetskyi, V. L.; Ogloblya, O. V.; Prylutskyy, Yu I.; Rybalchenko, V. K.; Ritter, U.; Scharff, P.

2018-03-01

Sclerosing cholangitis is the liver disease of uncertain etiology, extremely unfavorable prognosis and lack of effective medication therapy. Therefore, the effect of water-soluble biocompatible C60 fullerenes (C60FAS) on the liver functional state on rat acute-cholangitis model was aimed to be discovered. Acute cholangitis was simulated by single α-naphthyl isothiocyanate (ANIT, 100 mg/kg) per os administration; C60FAS (0.5 mg/kg) was administered either per os or intraperitoneally in 24 and 48 h after ANIT ingestion, and in 72 h the animals were sacrificed. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), the total and direct bilirubin, creatinine and urea in the blood serum were determined, and the liver morphological state was assessed. In animals experienced ANIT-induced acute cholangitis, the total and direct bilirubin, creatinine, ALT, AST, ALP and LDH 1.5-4-fold increase were observed, indicating cytolysis of hepatocytes, cholestasis, and renal dysfunction. The features of periductal fibrosis, biliary epithelium atrophy, and portal-portal linking septa formation were detected, confirming the sclerosing cholangitis development. C60FAS promoted to the normalization of direct and total bilirubin levels, the ALT activity and diminution of fibrotic features. In addition, C60FAS intraperitoneal administration also normalized the ALP activity, indicating the attenuation of disease symptoms. However, the AST activity and creatinine level remained unchanged, and the LDH activity even increased, manifesting the partial persistence of cholestasis and renal dysfunction. Thus, the therapeutic application of C60FAS promotes a partial protection of liver against cholangitis.

[Renal elastography].

PubMed

Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

2016-04-01

Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Bloodstream infections in patients with liver cirrhosis

PubMed Central

Bartoletti, Michele; Giannella, Maddalena; Lewis, Russell Edward; Viale, Pierluigi

2016-01-01

ABSTRACT Bloodstream infections are a serious complication in patients with liver cirrhosis. Dysregulated intestinal bacterial translocation is the predominant pathophysiological mechanism of infections in this setting. For this reason enteric Gram-negative bacteria are commonly encountered as the first etiological cause of infection. However, through the years, the improvement in the management of cirrhosis, the recourse to invasive procedures and the global spread of multidrug resistant pathogens have importantly changed the current epidemiology. Bloodstream infections in cirrhotic patients are characterized by high mortality rate and complications including metastatic infections, infective endocarditis, and endotipsitis (or transjugular intrahepatic portosystemic shunt-related infection). For this reason early identification of patients at risk for mortality and appropriated therapeutic management is mandatory. Liver cirrhosis can significantly change the pharmacokinetic behavior of antimicrobials. In fact hypoproteinaemia, ascitis and third space expansion and impairment of renal function can be translated in an unpredictable drug exposure. PMID:26864729

Bloodstream infections in patients with liver cirrhosis.

PubMed

Bartoletti, Michele; Giannella, Maddalena; Lewis, Russell Edward; Viale, Pierluigi

2016-04-02

Bloodstream infections are a serious complication in patients with liver cirrhosis. Dysregulated intestinal bacterial translocation is the predominant pathophysiological mechanism of infections in this setting. For this reason enteric Gram-negative bacteria are commonly encountered as the first etiological cause of infection. However, through the years, the improvement in the management of cirrhosis, the recourse to invasive procedures and the global spread of multidrug resistant pathogens have importantly changed the current epidemiology. Bloodstream infections in cirrhotic patients are characterized by high mortality rate and complications including metastatic infections, infective endocarditis, and endotipsitis (or transjugular intrahepatic portosystemic shunt-related infection). For this reason early identification of patients at risk for mortality and appropriated therapeutic management is mandatory. Liver cirrhosis can significantly change the pharmacokinetic behavior of antimicrobials. In fact hypoproteinaemia, ascitis and third space expansion and impairment of renal function can be translated in an unpredictable drug exposure.

Alcohol addiction - the safety of available approved treatment options.

PubMed

Antonelli, Mariangela; Ferrulli, Anna; Sestito, Luisa; Vassallo, Gabriele A; Tarli, Claudia; Mosoni, Carolina; Rando, Maria M; Mirijello, Antonio; Gasbarrini, Antonio; Addolorato, Giovanni

2018-02-01

Alcohol Use Disorders (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a 'temporary recommendation for use' in France. Areas covered: The safety of the above mentioned medications on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed. Expert opinion: Mechanism of action and metabolism of these drugs as well as patients' clinical characteristics can affect the safety of treatment. All approved medications are valid tools for the treatment of AUD in patients without advanced liver disease. For some drugs, attention should be paid to patients with renal failure and medications may be used with caution, adjusting the dosage according to kidney function. In patients with AUD and advanced liver disease, at present only baclofen has been formally tested in randomized controlled trials showing its safety in this population.

Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-07-01

Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

Investigation of possible interference by digoxin-like immunoreactive substances on the Architect iDigoxin CMIA in serum samples from pregnant women, and patients with liver disease, renal insufficiency, critical illness, and kidney and liver transplant.

PubMed

Lampon, Natalia; Pampin, Fernando; Tutor, J Carlos

2012-01-01

Although the possible interference of digoxin-like immunoreactive substances (DLIS) on the Architect iDigoxin chemiluminiscent microparticle immunoassay (CMIA) has been emphasized by the manufacturer, a specific study about this subject has still not been carried out. Apparent serum digoxin concentrations were determined using the Architect iDigoxin CMIA from Abbott Laboratories in digoxin-free pregnant women (n = 50), and patients with liver disease (n = 50), renal insufficiency (n = 50), kidney (n = 25) or liver (n = 25) transplant, and critical illness (n = 50). In all of the patients included in this study, apparent serum digoxin concentrations were lower than the correspondent quantification limit (< 0.30 microg/L). The Architect iDigoxin CMIA assay would be relatively free from endogenous DLIS positive interferences.

Measurements of renal shear wave velocities in chronic kidney disease patients.

PubMed

Sasaki, Yutaka; Hirooka, Yoshiki; Kawashima, Hiroki; Ishikawa, Takuya; Takeshita, Kyosuke; Goto, Hidemi

2018-07-01

Background Chronic kidney disease (CKD) patients have advanced glomerulosclerosis and renal interstitial fibrosis. Shear wave elastography (SWE) is useful to diagnose liver fibrosis. However, there are few data available regarding evaluation of kidney function on the use of SWE. Purpose To assess the utility of SWE by evaluating the correlation between renal function and renal elasticity using SWE. Material and Methods A total of 187 participants who had available serum creatinine levels and also underwent SWE of the kidney using a transabdominal ultrasonography were recruited at Nagoya University Hospital. We measured the depth of the shear wave (SW) in the right and left kidneys and calculated the measurement success rates. The glomerular filtration rate (GFR) classification and shear wave value (SWV) were compared. Results The success rates of the right and left kidneys were 93.6% and 71.6%, respectively. Based on these results, the correlation between GFR classification and SWV were analyzed in only the right kidneys because the success rates and the number of enrolled patients were low for the left kidney. There were significant differences found between G1 and G3a, G2 and G3a, G3a and G3b, G3a and G4, and G3a and G5. SWV significantly negatively and positively correlated with the G2-G3a and G3a-G3b classifications. Conclusion There is no correlation between renal function and SW. However, we can diagnose the progression to the CKD stages G3a and G3b by observing the changes over time using the SWV.

Are liver and renal lesions in East Greenland polar bears (Ursus maritimus) associated with high mercury levels?

PubMed

Sonne, Christian; Dietz, Rune; Leifsson, Pall S; Asmund, Gert; Born, Erik W; Kirkegaard, Maja

2007-04-17

In the Arctic, polar bears (Ursus maritimus) bio-accumulate mercury as they prey on polluted ringed seals (Phoca hispida) and bearded seals (Erignathus barbatus). Studies have shown that polar bears from East Greenland are among the most mercury polluted species in the Arctic. It is unknown whether these levels are toxic to liver and kidney tissue. We investigated the histopathological impact from anthropogenic long-range transported mercury on East Greenland polar bear liver (n = 59) and kidney (n = 57) tissues. Liver mercury levels ranged from 1.1-35.6 microg/g wet weight and renal levels ranged from 1-50 microg/g wet weight, of which 2 liver values and 9 kidney values were above known toxic threshold level of 30 microg/g wet weight in terrestrial mammals. Evaluated from age-correcting ANCOVA analyses, liver mercury levels were significantly higher in individuals with visible Ito cells (p < 0.02) and a similar trend was found for lipid granulomas (p = 0.07). Liver mercury levels were significantly lower in individuals with portal bile duct proliferation/fibrosis (p = 0.007) and a similar trend was found for proximal convoluted tubular hyalinisation in renal tissue (p = 0.07). Based on these relationships and the nature of the chronic inflammation we conclude that the lesions were likely a result of recurrent infections and ageing but that long-term exposure to mercury could not be excluded as a co-factor. The information is important as it is likely that tropospheric mercury depletion events will continue to increase the concentrations of this toxic heavy metal in the Sub Arctic and Arctic marine food webs.

Urinary L-FABP as a marker of vesicoureteral reflux in children: could it also have a protective effect on the kidney?

PubMed

Benzer, Meryem; Tekin Neijmann, Sebnem; Gültekin, Nazlı Dilay; Uluturk Tekin, Aslı

2017-01-01

Liver-type fatty acid-binding protein is a small cytoplasmic protein which is expressed in the human renal proximal tubular epithelium and synthesized in response to renal tubular injury. The aim of the present study was to investigate the importance of urinary liver-type fatty acid-binding protein levels in children who diagnosed with vesicoureteral reflux. Fifty-six patients with vesicoureteral reflux and 51 healthy controls were enrolled to the study. The cases were divided into three groups as follows: group A-the controls, group B-the patients who had renal parenchymal scarring and group C-the patients who had no scarring. Urinary liver-type fatty acid-binding protein was measured by enzyme-linked immunosorbent assay method. Creatinine was measured by modified Jaffe method, protein was measured by turbidimetric method, and urine density was determined by using the "falling drop" procedure. Urinary liver-type fatty acid-binding protein and urinary liver-type fatty acid-binding protein/creatinine levels were significantly higher in the whole patient group than in the controls (p = 0.016, 0.006). Significant differences were also determined by comparing the three groups (p = 0.015, 0.014), and those levels were found as significantly higher in group C. Urinary liver-type fatty acid-binding protein was considered to be helpful for the diagnosis of vesicoureteral reflux, and also it might contribute to understand the mechanisms causing scar tissue formation especially for the patients who had vesicoureteral reflux. Further clinical and experimental investigations are required to elucidate in detail the physiology of liver-type fatty acid-binding protein.

The value of "liver windows" settings in the detection of small renal cell carcinomas on unenhanced computed tomography.

PubMed

Sahi, Kamal; Jackson, Stuart; Wiebe, Edward; Armstrong, Gavin; Winters, Sean; Moore, Ronald; Low, Gavin

2014-02-01

To assess if "liver window" settings improve the conspicuity of small renal cell carcinomas (RCC). Patients were analysed from our institution's pathology-confirmed RCC database that included the following: (1) stage T1a RCCs, (2) an unenhanced computed tomography (CT) abdomen performed ≤ 6 months before histologic diagnosis, and (3) age ≥ 17 years. Patients with multiple tumours, prior nephrectomy, von Hippel-Lindau disease, and polycystic kidney disease were excluded. The unenhanced CT was analysed, and the tumour locations were confirmed by using corresponding contrast-enhanced CT or magnetic resonance imaging studies. Representative single-slice axial, coronal, and sagittal unenhanced CT images were acquired in "soft tissue windows" (width, 400 Hounsfield unit (HU); level, 40 HU) and liver windows (width, 150 HU; level, 88 HU). In addition, single-slice axial, coronal, and sagittal unenhanced CT images of nontumourous renal tissue (obtained from the same cases) were acquired in soft tissue windows and liver windows. These data sets were randomized, unpaired, and were presented independently to 3 blinded radiologists for analysis. The presence or absence of suspicious findings for tumour was scored on a 5-point confidence scale. Eighty-three of 415 patients met the study criteria. Receiver operating characteristics (ROC) analysis, t test analysis, and kappa analysis were used. ROC analysis showed statistically superior diagnostic performance for liver windows compared with soft tissue windows (area under the curve of 0.923 vs 0.879; P = .0002). Kappa statistics showed "good" vs "moderate" agreement between readers for liver windows compared with soft tissue windows. Use of liver windows settings improves the detection of small RCCs on the unenhanced CT. Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Outbreak of carbon tetrachloride poisoning in a color printing factory related to the use of isopropyl alcohol and an air conditioning system in Taiwan.

PubMed

Deng, J F; Wang, J D; Shih, T S; Lan, F L

1987-01-01

Three workers from a color printing factory were admitted to community hospitals in 1985 with manifestations of acute hepatitis. One of the three had superimposed acute renal failure and pulmonary edema. An investigation was subsequently conducted at the plant to determine the etiology of the outbreak and the prevalence of liver disease among the remaining workers. Comprehensive medical evaluations were conducted, which included physical examinations, liver function tests, and serological screening for hepatitis. Seventeen of 25 workers from the plant had abnormal liver function tests 10 days after the outbreak, and a significant association was found between the presence of abnormal liver function tests and a history of recently having worked inside any of three rooms in which an interconnecting air conditioning system had been installed to cool the printing machines. After further investigation, it was determined that the incident occurred following inadvertent use of carbon tetrachloride to clean a pump in the printing machine. A simulation of the pump cleaning operation revealed ambient air levels of carbon tetrachloride of 300-500 ppm. Ultimately, it was concluded that the outbreak was in all likelihood due to the combined use of carbon tetrachloride and isopropyl alcohol in the cleaning operation. This outbreak underscores the importance of adopting appropriate industrial hygiene measures in a rapidly industrializing nation such as Taiwan.

Trends in radiopharmaceutical dispensing in a regional nuclear pharmacy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basmadjian, G.P.; Johnston, J.; Barker, K.

1982-11-01

Dispensing trends for radiopharmaceuticals at a regional nuclear pharmacy over a 51-month period were studied. dispensing records of a regional nuclear pharmacy were analyzed with a forecasting procedure that uses univariate time data to produce time trends and autoregressive models. The overall number of prescriptions increased from 3500 to 5500 per quarter. Radiopharmaceuticals used in nuclear cardiology studies increased from less than 0.1% to 17.5% of total prescriptions dispensed, while radiopharmaceuticals used for brain imaging showed a steady decline from 29% to 11% of total prescriptions dispensed. The demand for other radiopharmaceuticals increased in areas such as renal studies, bonemore » studies, lung studies, liver-function studies, and /sup 67/Ga tumor-uptake studies, and declined slightly for static liver studies. Changes in dispensing trends for radiopharmaceuticals will continue as the practice of nuclear medicine concentrates more on functional studies and as newer imaging techniques become used for other purposes.« less

Histopathology and biochemistry analysis of the interaction between sunitinib and paracetamol in mice.

PubMed

Lim, Adeline Yl; Segarra, Ignacio; Chakravarthi, Srikumar; Akram, Sufyan; Judson, John P

2010-10-15

Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration. Group-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p < 0.05. Hepatic histopathology showed vascular congestion in group-B; mild congestion in group-C (but lesser than in group-B and D). In group-D, at low doses of sunitinib, lesser damage than in group-B occurred but larger changes including congestion were observed at high sunitinib doses. BUN levels were higher (p < 0.05) for group-B (33.81 ± 5.68 mg/dL) and group-D (range 35.01 ± 6.95 U/L to 52.85 ± 12.53 U/L) compared to group-A (15.60 ± 2.17 mg/dL) and group-C (range 17.50 ± 1.25 U/L to 26.68 ± 6.05 U/L). Creatinine remained unchanged. Renal congestion and necrosis was lower in group-C than group-B but was higher in group-D (p > 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs. Paracetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended.

Histopathology and biochemistry analysis of the interaction between sunitinib and paracetamol in mice

PubMed Central

2010-01-01

Background Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration. Results Group-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p < 0.05. Hepatic histopathology showed vascular congestion in group-B; mild congestion in group-C (but lesser than in group-B and D). In group-D, at low doses of sunitinib, lesser damage than in group-B occurred but larger changes including congestion were observed at high sunitinib doses. BUN levels were higher (p < 0.05) for group-B (33.81 ± 5.68 mg/dL) and group-D (range 35.01 ± 6.95 U/L to 52.85 ± 12.53 U/L) compared to group-A (15.60 ± 2.17 mg/dL) and group-C (range 17.50 ± 1.25 U/L to 26.68 ± 6.05 U/L). Creatinine remained unchanged. Renal congestion and necrosis was lower in group-C than group-B but was higher in group-D (p > 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs. Conclusions Paracetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended. PMID:20950441

Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl4-induced liver injury.

PubMed

Guo, Qing; Zhang, Qian-Qian; Chen, Jia-Qing; Zhang, Wei; Qiu, Hong-Cong; Zhang, Zun-Jian; Liu, Bu-Ming; Xu, Feng-Guo

2017-07-01

Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl 4 -induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl 4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl 4 -induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl 4 -induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Systemic effect of mineral aggregate-based cements: histopathological analysis in rats

PubMed Central

Garcia, Lucas da Fonseca Roberti; Huck, Claudia; Magalhães, Fernando Augusto Cintra; de Souza, Pedro Paulo Chaves; de Souza Costa, Carlos Alberto

2017-01-01

Abstract Objective: Several studies reported the local tissue reaction caused by mineral aggregate-based cements. However, few studies have investigated the systemic effects promoted by these cements on liver and kidney when directly applied to connective tissue. The purpose of this in vivo study was to investigate the systemic effect of mineral aggregate-based cements on the livers and kidneys of rats. Material and Methods: Samples of Mineral Trioxide Aggregate (MTA) and a calcium aluminate-based cement (EndoBinder) containing different radiopacifiers were implanted into the dorsum of 40 rats. After 7 and 30 d, samples of subcutaneous, liver and kidney tissues were submitted to histopathological analysis. A score (0-3) was used to grade the inflammatory reaction. Blood samples were collected to evaluate changes in hepatic and renal functions of animals. Results: The moderate inflammatory reaction (2) observed for 7 d in the subcutaneous tissue decreased with time for all cements. The thickness of inflammatory capsules also presented a significant decrease with time (P<.05). Systemically, all cements caused adverse inflammatory reactions in the liver and kidney, being more evident for MTA, persisting until the end of the analysis. Liver functions increased significantly for MTA during 30 d (P<.05). Conclusion: The different cements induced to a locally limited inflammatory reaction. However, from the systemic point of view, the cements promoted significant inflammatory reactions in the liver and kidney. For MTA, the reactions were more accentuated. PMID:29211283

Applying standardized uptake values in gallium-67-citrate single-photon emission computed tomography/computed tomography studies and their correlation with blood test results in representative organs.

PubMed

Toriihara, Akira; Daisaki, Hiromitsu; Yamaguchi, Akihiro; Yoshida, Katsuya; Isogai, Jun; Tateishi, Ukihide

2018-05-21

Recently, semiquantitative analysis using standardized uptake value (SUV) has been introduced in bone single-photon emission computed tomography/computed tomography (SPECT/CT). Our purposes were to apply SUV-based semiquantitative analytic method for gallium-67 (Ga)-citrate SPECT/CT and to evaluate correlation between SUV of physiological uptake and blood test results in representative organs. The accuracy of semiquantitative method was validated using an National Electrical Manufacturers Association body phantom study (radioactivity ratio of sphere : background=4 : 1). Thereafter, 59 patients (34 male and 25 female; mean age, 66.9 years) who had undergone Ga-citrate SPECT/CT were retrospectively enrolled in the study. A mean SUV of physiological uptake was calculated for the following organs: the lungs, right atrium, liver, kidneys, spleen, gluteal muscles, and bone marrow. The correlation between physiological uptakes and blood test results was evaluated using Pearson's correlation coefficient. The phantom study revealed only 1% error between theoretical and actual SUVs in the background, suggesting the sufficient accuracy of scatter and attenuation corrections. However, a partial volume effect could not be overlooked, particularly in small spheres with a diameter of less than 28 mm. The highest mean SUV was observed in the liver (range: 0.44-4.64), followed by bone marrow (range: 0.33-3.60), spleen (range: 0.52-2.12), and kidneys (range: 0.42-1.45). There was no significant correlation between hepatic uptake and liver function, renal uptake and renal function, or bone marrow uptake and blood cell count (P>0.05). The physiological uptake in Ga-citrate SPECT/CT can be represented as SUVs, which are not significantly correlated with corresponding blood test results.

Enteric-coated mycophenolate sodium experience in liver transplant patients.

PubMed

Cantisani, G P C; Zanotelli, M L; Gleisner, A L M; de Mello Brandão, A; Marroni, C A

2006-04-01

Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.

Different behaviour of BK-virus infection in liver transplant recipients

PubMed Central

Umbro, Ilaria; Tinti, Francesca; Muiesan, Paolo; Mitterhofer, Anna Paola

2016-01-01

Polyomavirus BK (BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A PubMed search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English-language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease (CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication. PMID:26819520

Metabolic cooperation of ascorbic acid and glutathione in normal and vitamin C-deficient ODS rats.

PubMed

Wang, Y; Kashiba, M; Kasahara, E; Tsuchiya, M; Sato, E F; Utsumi, K; Inoue, M

2001-01-01

Although the coordination of various antioxidants is important for the protection of organisms from oxidative stress, dynamic aspects of the interaction of endogenous antioxidants in vivo remain to be elucidated. We studied the metabolic coordination of two naturally occurring water-soluble antioxidants, ascorbic acid (AA) and reduced glutathione (GSH), in liver, kidney and plasma of control and scurvy-prone osteogenic disorder Shionogi (ODS) rats that hereditarily lack the ability to synthesize AA. When supplemented with AA, its levels in liver and kidney of ODS rats increased to similar levels of those in control rats. Hepato-renal levels of glutathione were similar with the two animal groups except for the slight increase in its hepatic levels in AA-supplemented ODS rats. Administration of L-buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, rapidly decreased the hepato-renal levels of glutathione in a biphasic manner, a rapid phase followed by a slower phase. Kinetic analysis revealed that glutathione turnover was enhanced significantly in liver mitochondria and renal cytosol of ODS rats. Administration of BSO significantly increased AA levels in the liver and kidney of control rats but decreased them in AA-supplemented ODS rats. Kinetic analysis revealed that AA is synthesized by control rat liver by some BSO-enhanced mechanism and the de novo synthesized AA is transferred to the kidney. Such a coordination of the metabolism of GSH and AA in liver and kidney is suppressed in AA-deficient ODS rats. These and other results suggest that the metabolism of AA and GSH forms a compensatory network by which oxidative stress can be decreased.

Immunopathologic effects of scorpion venom on hepato-renal tissues: Involvement of lipid derived inflammatory mediators.

PubMed

Lamraoui, Amal; Adi-Bessalem, Sonia; Laraba-Djebari, Fatima

2015-10-01

Scorpion venoms are known to cause different inflammatory disorders through complex mechanisms in various tissues. In the study here, the involvement of phospholipase A2 (PLA2) and cyclo-oxygenase (COX)-derived metabolites in hepatic and renal inflammation responses were examined. Mice were envenomed with Androctonus australis hector scorpion venom in the absence or presence of inhibitors that can interfere with lipid inflammatory mediator synthesis, i.e., dexamethasone (PLA2 inhibitor), indomethacin (non-selective COX-1/COX-2 inhibitor), or celecoxib (selective COX-2 inhibitor). The inflammatory response was assessed by evaluating vascular permeability changes, inflammatory cell infiltration, oxidative/nitrosative stress marker levels, and by histologic and functional analyses of the liver and kidney. Results revealed that the venom alone induced an inflammatory response in this tissues marked by increased microvascular permeability and inflammatory cell infiltration, increases in levels of nitric oxide and lipid peroxidation, and decreases in antioxidant defense. Moreover, significant alterations in the histological architecture of these organs were associated with increased serum levels of some metabolic enzymes, as well as urea and uric acid. Pre-treatment of mice with dexamethasone led to significant decreases of the inflammatory disorders in the hepatic parenchyma; celecoxib pre-treatment seemed to be more effective against renal inflammation. Indomethacin pre-treatment only slightly reduced the inflammatory disorders in the tissues. These results suggest that the induced inflammation response in liver was mediated mainly by PLA2 activation, while the renal inflammatory process was mediated by prostaglandin formation by COX-2. These findings provide additional insight toward the understanding of activated pathways and related mechanisms involved in scorpion envenoming syndrome.

Acute hepatitis E in a renal transplantation recipient: a case report.

PubMed

Shindo, Mitsutoshi; Takemae, Hiroaki; Kubo, Takafumi; Soeno, Masatsugu; Ando, Tetsuo; Morishita, Yoshiyuki

2018-01-01

Hepatitis E is caused by infection with the hepatitis E virus (HEV). HEV is transmitted orally via HEV-contaminated food or drink. Hepatitis E usually shows mild symptoms and is self-limiting in the general population; however, it may progress to chronic hepatitis in immunosuppressed patients such as recipients of organ transplantation. However, a few cases of acute hepatitis E have been reported in organ transplantation recipients. We herein report a case of acute hepatitis E in a 31-year-old male renal transplant recipient. The patient underwent renal transplantation 2 years ago, and his postoperative course was uneventful without rejection. After complaining of general fatigue and low-grade fever for 1 week, he was referred to and admitted to our hospital. Careful interview revealed that he ate undercooked pork 10 weeks prior. Blood analysis revealed liver dysfunction but was serologically negative for hepatitis A, B and C virus, cytomegalovirus infection and collagen diseases. Immunoglobulin A antibody against hepatitis E virus (HEV-IgA) was also negative at that point. After 2 weeks of admission, HEV-IgA and HEV-RNA were measured again as hepatitis E could not be ruled out due to history of ingestion of undercooked meat that may have been contaminated with HEV. At that time, HEV-IgA and HEV-RNA (genotype 3) were positive. Thus, an acute hepatitis E was diagnosed. His liver function gradually improved to within the normal range, and HEV-IgA and HEV-RNA were negative at 11 weeks after admission. In conclusion, we describe here a case of acute hepatitis E in a renal transplant recipient. Careful interview regarding the possibility of ingestion of HEV-contaminated food and repeated measurements of HEV-IgA were helpful in finalizing a diagnosis.

Acetaminophen (Paracetamol) induced acute liver failure - A social problem in an era of increasing tendency to self-treatment.

PubMed

Wróblewski, Tadeusz; Kobryń, Konrad; Kozieł, Sławomir; Ołdakowska-Jedynak, Urszula; Pinkas, Jarosław; Danielewicz, Roman; Ziarkiewicz-Wróblewska, Bogna; Krawczyk, Marek

2015-01-01

The widespread availability of medication without prescription, so-called over the counter (OTC), and the rapid development of health consciousness of Poles is associated with broad access to medical information in the mass media. This causes patients to recognize their own disease, cancel doctor's appointments, and begin self-treatment. This time and money-saving behavior, often signaled by pain, usually leads to the treatment of symptoms alone, without seeking the cause of the disease.The aim of the study was to present life-threatening paracetamol poisoning, and the treatment of acute liver failure. In 2002-2014, 35 patients were hospitalized due to acute paracetamol poisoning: 17 female and 18 male patients aged between 17-59 (mean 32.3 years). Patients were treated in the surgical intensive care unit, where their parameters of liver and renal function were continuously monitored. If there was no improvement in the liver function, patients underwent albumin dialysis with the Prometheus system and were qualified for liver transplantation (LTx). 26 patients were treated pharmacologically and 7 out of 9 patients who underwent LTx were dialyzed. Overall, 11 patients had 26 albumin dialysis in total; 4 patients died - 1 post-transplant and 3 pre-transplant. Paracetamol is the cause of many poisonings resulting from the lack of public awareness about toxic interactions with alcohol, and suicide attempts. Acetaminophen-induced acute liver failure concerns a small percentage of patients but can be successfully treated with albumin dialysis, and in extreme cases by liver transplantation.

Photobiogenesis and metabolism of vitamin D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holick, M.F.; Clark, M.B.

1978-10-01

Provitamin D3 (7-dehydrocholesterol) is converted to previtamin D3 by the action of ultraviolet radiation on the skin. Previtamin D3 thermally isomerizes to vitamin D3 in the skin and the vitamin is then transported to the liver on the vitamin D-binding protein. Although there are extrahepatic vitamin D-25-hydroxylases, the liver is the major site for the 25-hydroxylation of vitamin D. In response to hypocalcemia and hypophosphatemia, 25-OH-D is metabolized by a renal-cytochrome. Parathyroid hormone has clearly been shown to be a trophin for the renal synthesis of 1,25(OH)2D; however, the role and significance of the adrenal steroids, or gonadal and pituitarymore » hormones, on the renal 25-OH-D-1alpha-hydroxylase is not well defined.« less

Droxidopa, an oral norepinephrine precursor, improves hemodynamic and renal alterations of portal hypertensive rats.

PubMed

Coll, Mar; Rodriguez, Sarai; Raurell, Imma; Ezkurdia, Nahia; Brull, Astrid; Augustin, Salvador; Guardia, Jaime; Esteban, Rafael; Martell, María; Genescà, Joan

2012-11-01

We aimed to evaluate the effects of droxidopa (an oral synthetic precursor of norepinephrine) on the hemodynamic and renal alterations of portal hypertensive rats. Sham, portal vein-ligated (PVL), and 4-week biliary duct-ligated (BDL) rats received a single oral dose of droxidopa (25-50 mg/kg) or vehicle and hemodynamic parameters were monitored for 2 hours. Two groups of BDL and cirrhotic rats induced by carbon tetrachloride (CCl(4) ) were treated for 5 days with droxidopa (15 mg/kg, twice daily, orally); hemodynamic parameters and blood and urinary parameters were assessed. The droxidopa effect on the Rho kinase (RhoK) / protein kinase B (AKT) / endothelial nitric oxide synthase (eNOS) pathways was analyzed by western blot in superior mesenteric artery (SMA). The acute administration of droxidopa in PVL and BDL rats caused a significant and maintained increase in arterial pressure and mesenteric arterial resistance, with a significant decrease of mesenteric arterial and portal blood flow, without changing portal pressure and renal blood flow. Two-hour diuresis greatly increased. Carbidopa (DOPA decarboxylase inhibitor) blunted all effects of droxidopa. Chronic droxidopa therapy in BDL rats produced the same beneficial hemodynamic effects observed in the acute study, did not alter liver function parameters, and caused a 50% increase in 24-hour diuresis volume (7.4 ± 0.9 mL/100g in BDL vehicle versus 11.8 ± 2.5 mL/100g in BDL droxidopa; P = 0.01). Droxidopa-treated rats also showed a decreased ratio of p-eNOS/eNOS and p-AKT/AKT and increased activity of RhoK in SMA. The same chronic treatment in CCl(4) rats caused similar hemodynamic effects and produced significant increases in diuresis volume and 24-hour natriuresis (0.08 ± 0.02 mmol/100g in CCl(4) vehicle versus 0.23 ± 0.03 mmol/100g in CCl(4) droxidopa; P = 0.014). Droxidopa might be an effective therapeutic agent for hemodynamic and renal alterations of liver cirrhosis and should be tested in cirrhosis patients. Copyright © 2012 American Association for the Study of Liver Diseases.

Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions.

PubMed

Perreault, Martin; Wunsch, Ewa; Białek, Andrzej; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Poirier, Guy G; Milkiewicz, Piotr; Barbier, Olivier

2018-01-01

Biliary obstruction, a severe cholestatic complication, causes accumulation of toxic bile acids (BAs) in liver cells. Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic BAs. Using liquid chromatography coupled to tandem mass spectrometry, 11 BA glucuronide (-G) species were quantified in prebiliary and postbiliary stenting serum and urine samples from 17 patients with biliary obstruction. Stenting caused glucuronide- and fluid-specific changes in BA-G levels and BA-G/BA metabolic ratios. In vitro glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lower K M values, the two tissues shared similar glucuronidation capacities for BAs. By contrast, major differences between the two tissues were observed when four human BA-conjugating UGTs 1A3, 1A4, 2B4, and 2B7 were analyzed for mRNA and protein levels. Notably, the BA-24G producing UGT1A3 enzyme, abundant in the liver, was not detected in kidney microsomes. In conclusion, the circulating and urinary BA-G profiles are hugely impacted under severe cholestasis. The similar BA-glucuronidating abilities of hepatic and renal extracts suggest that both the liver and kidney may contribute to the urine BA-G pool.

Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions

PubMed Central

Perreault, Martin; Białek, Andrzej; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Poirier, Guy G.

2018-01-01

Biliary obstruction, a severe cholestatic complication, causes accumulation of toxic bile acids (BAs) in liver cells. Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic BAs. Using liquid chromatography coupled to tandem mass spectrometry, 11 BA glucuronide (-G) species were quantified in prebiliary and postbiliary stenting serum and urine samples from 17 patients with biliary obstruction. Stenting caused glucuronide- and fluid-specific changes in BA-G levels and BA-G/BA metabolic ratios. In vitro glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lower KM values, the two tissues shared similar glucuronidation capacities for BAs. By contrast, major differences between the two tissues were observed when four human BA-conjugating UGTs 1A3, 1A4, 2B4, and 2B7 were analyzed for mRNA and protein levels. Notably, the BA-24G producing UGT1A3 enzyme, abundant in the liver, was not detected in kidney microsomes. In conclusion, the circulating and urinary BA-G profiles are hugely impacted under severe cholestasis. The similar BA-glucuronidating abilities of hepatic and renal extracts suggest that both the liver and kidney may contribute to the urine BA-G pool. PMID:29850459

Metabolic and hemodynamic effects of sodium-dependent glucose cotransporter 2 inhibitors on cardio-renal protection in the treatment of patients with type 2 diabetes mellitus.

PubMed

Kashiwagi, Atsunori; Maegawa, Hiroshi

2017-07-01

The specific sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease because of urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole-body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors. In addition, SGLT2 inhibitors have profound hemodynamic effects including diuresis, dehydration, weight loss and lowering blood pressure. The most recent findings on SGLT2 inhibitors come from results of the Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes trial. SGLT2 inhibitors exert extremely unique and cardio-renal protection through metabolic and hemodynamic effects, with long-term durability on the reduction of blood glucose, bodyweight and blood pressure. Although a site of action of SGLT2 inhibitors is highly specific to inhibit renal glucose reabsorption, whole-body energy metabolism, and hemodynamic and renal functions are profoundly modulated during the treatment of SGLT2 inhibitors. Previous studies suggest multifactorial clinical benefits and safety concerns of SGLT2 inhibitors. Although ambivalent clinical results of this drug are still under active discussion, the present review summarizes promising recent evidence on the cardio-renal and metabolic benefits of SGLT2 inhibitors in the treatment of type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Application of regenerative medicine for kidney diseases.

PubMed

Yokoo, Takashi; Fukui, Akira; Kobayashi, Eiji

2007-01-01

Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF).The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application.

Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure

PubMed Central

Wang, Jiali; Xu, Jiankun; Liu, Waiching; Li, Yangde; Qin, Ling

2016-01-01

Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns. PMID:27210744

Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure

NASA Astrophysics Data System (ADS)

Wang, Jiali; Xu, Jiankun; Liu, Waiching; Li, Yangde; Qin, Ling

2016-05-01

Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns.

Concurrent use of methotrexate and celecoxib increases risk of silent liver fibrosis in rheumatoid arthritis patients with subclinical reduced kidney function.

PubMed

Park, Jin Su; Park, Min-Chan; Park, Yong-Beom; Lee, Soo-Kon; Lee, Sang-Won

2014-01-01

We evaluated the effects of concurrent use of methotrexate and celecoxib on silent liver and kidney damages in rheumatoid arthritis (RA) patients. We enrolled 92 RA patients with normal laboratory results related to liver and kidney functions, who had received methotrexate and celecoxib concurrently over 6 months. Liver stiffness measurement (LSM) using transient elastography and ultrasonography were performed along with blood and urine tests. Estimated glomerular filtration rate (eGFR) was calculated by both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) equations. Initial eGFR represented kidney function at the time of the initiation of celecoxib. The cutoff for abnormal LSM values was adopted as 5.3 kPa. The optimal cutoff of each eGFR for abnormal LSM values was also calculated. The median age of patients was 55 years old (74 women). The median LSM was 4.4 kPa and the median eGFRs and median initial eGFRs ranged from 89 to 99 mL/min/1.73 m(2). The cumulative doses of methotrexate and celecoxib and their concurrent administration duration did not affect LSM values and eGFRs. Both eGFRs were significantly associated with LSM values. Patients with initial eGFR(CKD-EPI), initial eGFR(MDRD), and eGFR(CKD-EPI) below each optimal cutoff had significantly high risks for silent liver fibrosis (RR 9.4, 10.3, and 4.4, p < 0.001, respectively). Both initial eGFRs (CKD-EPI and MDRD) and eGFR (CKD-EPI) were significant predictors for the development of silent liver fibrosis in RA patients who had received methotrexate and celecoxib concurrently for at least 6 months.

TAT-MTS-MCM fusion proteins reduce MMA levels and improve mitochondrial activity and liver function in MCM-deficient cells.

PubMed

Erlich-Hadad, Tal; Hadad, Rita; Feldman, Anat; Greif, Hagar; Lictenstein, Michal; Lorberboum-Galski, Haya

2018-03-01

Methylmalonic aciduria (MMA) is a disorder of organic acid metabolism resulting from a functional defect of the mitochondrial enzyme, methylmalonyl-CoA mutase (MCM). The main treatments for MMA patients are dietary restriction of propiogenic amino acids and carnitine supplementation. Liver or combined liver/kidney transplantation has been used to treat those with the most severe clinical manifestations. Thus, therapies are necessary to help improve quality of life and prevent liver, renal and neurological complications. Previously, we successfully used the TAT-MTS-Protein approach for replacing a number of mitochondrial-mutated proteins. In this targeted system, TAT, an 11 a.a peptide, which rapidly and efficiently can cross biological membranes, is fused to a mitochondrial targeting sequence (MTS), followed by the mitochondrial mature protein which sends the protein into the mitochondria. In the mitochondria, the TAT-MTS is cleaved off and the native protein integrates into its natural complexes and is fully functional. In this study, we used heterologous MTSs of human, nuclear-encoded mitochondrial proteins, to target the human MCM protein into the mitochondria. All fusion proteins reached the mitochondria and successfully underwent processing. Treatment of MMA patient fibroblasts with these fusion proteins restored mitochondrial activity such as ATP production, mitochondrial membrane potential and oxygen consumption, indicating the importance of mitochondrial function in this disease. Treatment with the fusion proteins enhanced cell viability and most importantly reduced MMA levels. Treatment also enhanced albumin and urea secretion in a CRISPR/Cas9-engineered HepG2 MUT (-/-) liver cell line. Therefore, we suggest using this TAT-MTS-Protein approach for the treatment of MMA. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Long-term rifaximin therapy as a primary prevention of hepatorenal syndrome.

PubMed

Ibrahim, El-Sayed; Alsebaey, Ayman; Zaghla, Hassan; Moawad Abdelmageed, Sabry; Gameel, Khalid; Abdelsameea, Eman

2017-11-01

Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis, with poor survival. Rifaximin is a gut-selective broad-spectrum antibiotic. The aim of this study was to evaluate the role of rifaximin as a primary prevention of HRS. Eighty patients with liver cirrhosis and ascites were enrolled. They were randomized into two groups: control (n=40) and rifaximin group (n=40). Baseline liver function tests, renal function tests, complete blood count, international normalized ratio, urine analysis, and abdominal ultrasonography were carried out. Rifaximin 550 mg was administered twice daily for 12 weeks. Renal functions were measured every 4 weeks with monitoring of HRS occurrence and possible precipitating factor. Both groups were matched for age, sex, virology, serum bilirubin, serum albumin, aspartate aminotransferase, alanine aminotransferase, hemoglobin, white blood cells, platelets, international normalized ratio, potassium, and Child-Pugh score. In contrast to the rifaximin group, the control group showed statistically significant serial blood urea nitrogen (18.84±7.17, 19.85±6.10, 21.54±4.79, and 22.96±5.82 mg/dl; P=0.001) and serum creatinine (0.94±0.25, 1.02±0.24, 1.12±0.16, and 1.21±0.17 mg/dl; P=0.001) levels. The overall blood urea nitrogen and serum creatinine change was statistically higher in the control group than the rifaximin group (20.8 vs. 18.24 mg/dl and 1.07 vs. 0.99 mg/dl, respectively). HRS developed more in the control group than the rifaximin group [9 (22.5%) vs. 2 (5%); P=0.048]. In both groups, HRS was precipitated by spontaneous bacterial peritonitis mainly and large volume paracentesis. The Child-Pugh score, control group, baseline serum sodium, and creatinine were predictors of HRS. Rifaximin may be useful as a primary prevention of HRS.

Efficacy of extracorporeal albumin dialysis for acute kidney injury due to cholestatic jaundice nephrotoxicity.

PubMed

Sens, Florence; Bacchetta, Justine; Rabeyrin, Maud; Juillard, Laurent

2016-07-07

We report a case of a 37-year-old man with Maturity Onset Diabetes of the Youth (MODY) type 5, admitted for an episode of cholestasis and a simultaneous acute kidney injury (AKI). Chronic liver disease was due to a mutation in the transcription factor 2 (TCF2) gene, thus highlighting the need for a close liver follow-up in these patients. AKI was attributed to a cholemic nephropathy based on the following rationale: (1) alternative diagnoses were actively ruled out; (2) the onset of AKI coincided with the onset of severe hyperbilirubinaemia; (3) renal pathology showed large bile tubular casts and a marked tubular necrosis and (4) creatinine serum dramatically decreased when bilirubin levels improved after the first sessions of extracorporeal albumin dialysis (ECAD), thus suggesting its role in renal recovery. Even though cholestasis can precipitate renal injury, the diagnosis of cholemic nephropathy could require a renal biopsy at times. Future studies should confirm the benefits of ECAD in cholemic nephropathy. 2016 BMJ Publishing Group Ltd.

Oral metastasis from primary transitional cell carcinoma of the renal pelvis: report of a case.

PubMed

Zhang, Y; Gu, Z-Y; Tian, Z; Yang, C; Cai, X-Y

2010-07-01

Transitional cell carcinoma of the renal pelvis is initially a slow growing tumor arising from the transitional epithelium of the mucous membrane of the renal pelvis. Recurrences occur in two forms: superficial bladder cancer and distant metastases. The common metastasis is in the lung, liver, brain and bone. Oral metastasis is seldom reported. The authors report an unusual case of transitional cell carcinoma of the renal pelvis metastasized to the oral cavity and lung simultaneously in a 74-year-old man, which occurred 1 year after a left nephroureterectomy. The patient underwent six courses of chemotherapy (gemcitabine, oxaliplatin, fluorouracil and nedaplatin), and received radiotherapy for the oral lesion. The symptoms were alleviated, but the tumor recurred in the oral cavity 2 years later. Brain and liver metastases were confirmed by CT. Repeated radiotherapy for oral metastasis was performed, but the patient died 4 years after the initial nephroureterectomy due to multiple metastases. Copyright 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

The para isomer of dinitrobenzene disrupts redox homeostasis in liver and kidney of male wistar rats.

PubMed

Sangodele, Janet Olayemi; Olaleye, Mary Tolulope; Monsees, Thomas K; Akinmoladun, Afolabi Clement

2017-07-01

Para - Dinitrobenzene (p -DNB) is one of the isomers of dinitrobenzene which have been detected as environmental toxicants. Skin irritation and organ toxicities are likely for industrial workers exposed to p -DNB. This study evaluated the effect of sub-chronic exposure of rats to p -DNB on cellular redox balance, hepatic and renal integrity. Forty eight male Wistar rats weighing 160-180 g were administered 50, 75, 1000 and 2000 mg/kg b.wt (body weight) of p -DNB or an equivalent volume of vehicle (control) orally and topically for 14 days. After the period of treatment, the activities of kidney and liver catalase (CAT), alkaline phosphatase (ALP) and superoxide dismutase (SOD) as well as extent of renal and hepatic lipid peroxidation (LPO) were determined. Serum ALP activity and plasma urea concentration were also evaluated. Compared with control animals, p -DNB -administered rats showed decrease in the body and relative kidney and liver weights as well as increased renal and hepatic hydrogen peroxide and lipid peroxidation levels accompanied by decreased superoxide dismutase and catalase activities. However, p -DNB caused a significant increase in plasma urea concentration and serum, liver and kidney ALP activities relative to control. In addition, p -DNB caused periportal infiltration, severe macro vesicular steatosis and hepatic necrosis in the liver. Our findings show that sub-chronic oral and sub-dermal administration of p -DNB may produce hepato-nephrotoxicity through oxidative stress.

[A case of Legionella pneumonia with multiple organ failure].

PubMed

Li, Jiali; Wen, Rui; Deng, Hong; Li, Qian

2016-06-28

Legionella pneumonia (LP) is a rare systemic infectious disease, which is often misdiagnosed by clinicians due to the atypical symptoms. A middle-aged man who suffered from fever and dyspnea was diagnosed as community acquired pneumonia (CAP) in Changsha Central Hospital in March 2015. The treatment was unsatisfied firstly. The patients showed further symptoms of rhabdomyolysis, acute liver and renal failure, and impaired neural functions, who was diagnosed as LP with multiple organ failure based on a positive test for Legionella antibody. The patient was recovered after treated with moxifloxacin combined with azithromycin and continuous renal replacement therapy. LP should be paid attention when patient was diagnosed as CAP and failed to be treated. The satisfied outcome is achieved after application of macrolide, quinolones and comprehensive treatments.

Early Allograft Dysfunction After Liver Transplantation Is Associated With Short- and Long-Term Kidney Function Impairment.

PubMed

Wadei, H M; Lee, D D; Croome, K P; Mai, M L; Golan, E; Brotman, R; Keaveny, A P; Taner, C B

2016-03-01

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Response of urinary liver-type fatty acid-binding protein to contrast media administration has a potential to predict one-year renal outcome in patients with ischemic heart disease.

PubMed

Fujita, Daishi; Takahashi, Masao; Doi, Kent; Abe, Mitsuru; Tazaki, Junichi; Kiyosue, Arihiro; Myojo, Masahiro; Ando, Jiro; Fujita, Hideo; Noiri, Eisei; Sugaya, Takeshi; Hirata, Yasunobu; Komuro, Issei

2015-05-01

Urinary liver-type fatty acid-binding proteins (uL-FABP) have recently been recognized as a useful biomarker for predicting contrast-induced nephropathy. Although accumulating studies have evaluated short-term outcomes, its prognostic value for long-term renal prognosis in patients undergoing coronary angiography (CAG) has not been fully examined. This study aimed to evaluate the predictive value of uL-FABP for long-term renal outcome in patients with ischemic heart disease (IHD). Consecutive 24 patients with impaired renal function (serum creatinine >1.2 mg/dL) who underwent CAG were enrolled. uL-FABP was measured before CAG, 24 and 48 h after CAG. The changes in estimated glomerular filtration rate (eGFR) throughout CAG and at 1 year later were compared with the uL-FABP levels. The patients with a greater decrease in eGFR 1 year later had higher uL-FABP levels at all points, but only the value at 48 h after CAG reached statistical significance (lower vs. higher decreased eGFR group, 4.61 ± 3.87 vs. 17.71 ± 12.96; P < 0.01). Measurement of uL-FABP at 48 h after CAG (48h-uL-FABP) showed better correlation with the change in eGFR (pre-CAG uL-FABP vs. 48h-uL-FABP: R = 0.27, P = 0.20 vs. R = 0.65, P < 0.01). Moreover, the high-pre and high-48h-uL-FABP group showed a significantly larger decrease in eGFR compared with the high-pre and low-48h-uL-FABP group (change in eGFR; 8.12 ± 4.06 vs. 1.25 ± 2.23 mL/min/1.73 m2, P < 0.01), although the baseline eGFR levels were similar between these two groups. In this pilot study, measurement of uL-FABP levels at 48 h after CAG may be useful in detecting renal damage, and in predicting 1-year renal outcome in IHD patients undergoing CAG.

Preliminary investigation of high-dose tranexamic acid for controlling intraoperative blood loss in patients undergoing spine correction surgery.

PubMed

Xie, Jingming; Lenke, Lawrence G; Li, Tao; Si, Yongyu; Zhao, Zhi; Wang, Yingsong; Zhang, Ying; Xiao, Jie

2015-04-01

With a significant increase in the number and complexity of spinal deformity corrective surgeries, blood loss, often requiring massive intraoperative transfusions, becomes a major limiting factor during surgery. This scenario is particularly during posterior vertebral column resection (PVCR), where extensive intraoperative blood loss may pose a major risk to the patient, preventing smooth execution of the procedure. Tranexamic Acid (TXA) has been used in cardiac and orthopedic surgeries, including major spinal surgeries, to reduce blood loss and transfusion requirements for decades. To assess the efficacy and safety of high doses of TXA in posterior spinal deformity corrective surgery, including PVCR procedures. A retrospective study from a single institution. Fifty-nine patients (age range 7 to 46 years old) with spinal deformities undergoing spinal corrective surgeries were included. The patients were divided into two groups: the TXA group (total of 26 patients, including 8 PVCR patients) and the control group (total of 33 patients, including 9 PVCR patients). The analyzed outcome measures included estimated intraoperative blood loss, real blood loss (RBL; blood loss/blood volume×100%), blood transfusion requirements, coagulation parameters, complete blood count, liver function, and renal function. Lower limb vein thrombus, symptomatic pulmonary embolism, symptomatic myocardial infarction, seizures, and acute renal failure were also recorded. Before skin incision, the patients in the TXA group received an intravenous loading dose of 100 mg/Kg over a 20-minute period, followed by a maintenance infusion of 10 mg/Kg/h until skin closure was completed. The patients in the control group received saline infusion of a similar volume. Statistics included estimated intraoperative blood loss, RBL, blood transfusion requirements, coagulation parameters, complete blood count, liver function, and renal function. All patients in this study were also carefully monitored for consciousness level, breathing status, chest tightness or pain, and urine output after surgery. These were done to detect the presence or absence of pulmonary embolism, myocardial infarction, seizures, and acute renal failure. Patients treated with TXA were examined via vascular ultrasound before and after surgery. There were no significant differences in the demographic or surgical traits between the two groups. The blood loss of the patients in the TXA group was 2,441±1,666 mL, whereas that of the control group patients was 4,789±4,719 mL. The difference was statistically significant (p<.05). The average RBL of the patients in the TXA group was 80.6%±49.6% versus 160.8%±163.1% in the control group (p<.05). The blood transfusion requirements for the patients in the TXA group were significantly less than that in the control group (p<.05). Blood loss, RBL, and blood transfusion requirements were all significantly lower in the TXA group, compared with the control group among both PVCR patients and non-PVCR patients. In the TXA group, there was an average of 57.4% reduced blood loss in patients who received PVCR and 39.8% in patients not receiving PVCR. There were no differences in liver and renal functions between the TXA and control groups. There was no lower limb vein thrombus, symptomatic myocardial infarction, symptomatic pulmonary embolism, seizures, or acute renal failure reported in the TXA group. In our study, high doses of TXA have been shown to effectively control blood loss and reduce the transfusion requirement. This effect was more apparent in patients receiving PVCR. No adverse drug reaction was recorded in the study. In the future, prospective randomized controlled trials to validate our results will be necessary. Future studies conducted on older patient cohort may also be necessary to confirm the safety of extending the use of TXA to the older patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Leukocyte Cell–Derived Chemotaxin 2–Associated Amyloidosis: A Recently Recognized Disease with Distinct Clinicopathologic Characteristics

PubMed Central

Dogan, Ahmet; Larsen, Christopher P.

2015-01-01

Amyloidosis derived from leukocyte cell–derived chemotaxin 2 is a recently recognized form of amyloidosis, and it has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of kidney and liver. The disease has a strong ethnic bias, affecting mainly Hispanics (particularly Mexicans). Additional ethnic groups prone to develop amyloidosis derived from leukocyte cell–derived chemotaxin 2 include Punjabis, First Nations people in British Columbia, and Native Americans. Most patients are elderly who present with chronic renal insufficiency and bland urinary sediment. Proteinuria is variable, being absent altogether in about one third of patients. Liver involvement is frequently an incidental finding. Amyloidosis derived from leukocyte cell–derived chemotaxin 2 deposits shows a characteristic distribution: in the kidney, there is consistent involvement of cortical interstitium, whereas in the liver, there is a preferential involvement of periportal and pericentral vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and IgA nephropathy being the most common. Patient survival is excellent, likely because of the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease. There is currently no efficacious therapy for amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis. Renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft. The pathogenesis of amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis has not yet been elucidated. It could be a result of leukocyte cell–derived chemotaxin 2 overexpression by hepatocytes either constitutively (controlled by yet-uncharacterized genetic defects) or secondary to hepatocellular damage. It is critical not to misdiagnose amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis as Ig light chain–derived amyloidosis to avoid harmful chemotherapy. PMID:25873265

Vascular toxicity of urea, a new "old player" in the pathogenesis of chronic renal failure induced cardiovascular diseases.

PubMed

Giardino, Ida; D'Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

2017-12-01

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure.

Vascular toxicity of urea, a new “old player” in the pathogenesis of chronic renal failure induced cardiovascular diseases

PubMed Central

D’Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

2017-01-01

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure. PMID:29483797

Short-term risk of liver and renal injury in hospitalized patients using micafungin: a multicentre cohort study.

PubMed

Schneeweiss, Sebastian; Carver, Peggy L; Datta, Kausik; Galar, Alicia; Johnson, Melissa D; Johnson, Matthew G; Marty, Francisco M; Nagel, Jerod; Najdzinowicz, Maryann; Saul, Melissa; Shoham, Shmuel; Silveira, Fernanda P; Varughese, Christy A; Wilck, Marissa; Weatherby, Lisa; Auton, Tim; Walker, Alexander M

2016-10-01

Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice. MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis. There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR = 0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR = 0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators. For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

PubMed

Gill, Katherine L; Houston, J Brian; Galetin, Aleksandra

2012-04-01

Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CL(int, UGT)) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CL(int, UGT) on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CL(int, UGT) in different tissues. Although BSA increased CL(int, UGT) in all tissues, the extent was tissue- and drug-dependent. Scaled CL(int, UGT) in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min(-1) · g tissue(-1) in liver, kidney, and intestinal microsomes. Renal CL(int, UGT) (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CL(int, UGT) for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CL(int, UGT) (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CL(int, UGT) is particularly important for UGT1A9 substrates.

Characterization of In Vitro Glucuronidation Clearance of a Range of Drugs in Human Kidney Microsomes: Comparison with Liver and Intestinal Glucuronidation and Impact of Albumin

PubMed Central

Gill, Katherine L.; Houston, J. Brian

2012-01-01

Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CLint, UGT) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CLint, UGT on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CLint, UGT in different tissues. Although BSA increased CLint, UGT in all tissues, the extent was tissue- and drug-dependent. Scaled CLint, UGT in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min−1 · g tissue−1 in liver, kidney, and intestinal microsomes. Renal CLint, UGT (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CLint, UGT for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CLint, UGT (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CLint, UGT is particularly important for UGT1A9 substrates. PMID:22275465

Roles of renal ammonia metabolism other than in acid-base homeostasis

PubMed Central

Weiner, I. David

2016-01-01

The importance of renal ammonia metabolism in acid-base homeostasis is well known. However, the effects of renal ammonia metabolism other than in acid-base homeostasis are not as widely recognized. First, ammonia differs from almost all other solutes in the urine in that it does not result from arterial delivery. Instead, ammonia is produced by the kidney and only a portion of the ammonia produced is excreted in the urine. The remainder is returned to the systemic circulation through the renal veins. In normal individuals, systemic ammonia addition is metabolized efficiently by the liver, but in patients with either acute or chronic liver disease, conditions that increase renal ammonia addition to the systemic circulation can cause precipitation and/or worsening of hyperammonemia. Second, ammonia appears to serve as an intra-renal paracrine signaling molecule. Hypokalemia increases proximal tubule ammonia production and secretion and it increases reabsorption in the thick ascending limb of the loop of Henle, thereby increasing delivery to the renal interstitium and the collecting duct. In the collecting duct, ammonia decreases potassium secretion and stimulates potassium reabsorption, thereby decreasing urinary potassium excretion and enabling feedback correction of the initiating hypokalemia. Finally, hypokalemia’s stimulation of renal ammonia metabolism and hypokalemia contributes to development of metabolic alkalosis, which can stimulate NaCl reabsorption and thereby contribute to the intravascular volume expansion, increased blood pressure and diuretic resistance that can develop with hypokalemia. In this review, we discuss the evidence supporting these novel non-acid-base roles of renal ammonia metabolism. PMID:27169421

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

PubMed

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats

PubMed Central

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine.

PubMed

Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H; Heinzow, Hauke S

2015-08-05

Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.

Urea.

PubMed

Wang, Hongkai; Ran, Jianhua; Jiang, Tao

2014-01-01

Urea is generated by the urea cycle enzymes, which are mainly in the liver but are also ubiquitously expressed at low levels in other tissues. The metabolic process is altered in several conditions such as by diets, hormones, and diseases. Urea is then eliminated through fluids, especially urine. Blood urea nitrogen (BUN) has been utilized to evaluate renal function for decades. New roles for urea in the urinary system, circulation system, respiratory system, digestive system, nervous system, etc., were reported lately, which suggests clinical significance of urea.

[Nutritional Assessment and Management for Patients with Chronic Liver Disease].

PubMed

Lee, Tae Hee

2018-04-25

When liver disease is severe, the prognosis can be worse if the patient is malnourished. Adequate nutritional support for patients with liver diseases can improve the patient's condition and prognosis. In the case of liver cirrhosis, malnutrition can occur due to a variety of causes, including poor oral intake, maldigestion, malabsorption, associated renal disease, and metabolic abnormalities. For a nutritional assessment, it is important to check the dietary intake, change in body composition, including anthropometry, and a functional assessment of muscle. Counselling and oral or enteral nutrition is preferred over parenteral nutrition as in other diseases. If esophageal varices are present, care should be taken when installing a feeding tube, but if there are ascites, percutaneous endoscopic gastrostomy is contraindicated because of the risk of complications. Calories of 30-35 kcal/kg/day and protein from 1.2 to 1.5 g/kg/day are appropriate. Protein restriction is unnecessary unless the hepatic encephalopathy is severe. A late evening snack and branched chain amino acids can be helpful. In the case of cholestasis, the supply of manganese and copper should be restricted. Sarcopenia in patients with liver cirrhosis is also prevalent and associated with the prognosis.

Primary hyperoxaluria in an adult presenting with end-stage renal failure together with hypercalcemia and hypothyroidism.

PubMed

Karadag, Serhat; Gursu, Meltem; Aydin, Zeki; Uzun, Sami; Dogan, Oner; Ozturk, Savas; Kazancioglu, Rumeyza

2011-10-01

Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease. © 2011 The Authors; Hemodialysis International © 2011 International Society for Hemodialysis.

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model

PubMed Central

Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

2016-01-01

The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet–fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of sublethal tubular cell injury. PMID:26752420

Recommendations of everolimus use in liver transplant.

PubMed

Rubín Suárez, Angel; Bilbao Aguirre, Itxarone; Fernández-Castroagudin, Javier; Pons Miñano, José Antonio; Salcedo Plaza, Magdalena; Varo Pérez, Evaristo; Prieto Castillo, Martín

2017-11-01

Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles. In patients with established kidney failure, initiating EVL may enable clinicians to reduce calcineurin inhibitors exposure, thereby contributing to the improved renal function of these patients. Although there is not sufficient evidence to recommend their use to prevent the recurrence of hepatocellular carcinoma and the progression of de novo tumours, they are used in this context in routine clinical practice. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

[A cohort study of longer-term impact of melamine contaminated formula on infant health].

PubMed

Wang, Pei-xin; Li, Hong-tian; Wang, Lin-lin; Zhang, Long; Zhou, Yu-bo; Liu, Jian-meng

2013-10-15

To prospectively evaluate the health status of infants with exposure to melamine-contaminated milk formula prior to September 2008. The cohort study was conducted in an area close to the manufacturer of Sanlu dairy products. There were three groups (n = 47 each). In September 2008, the exposure group I included infants with exposure to melamine and a diagnosis of renal abnormalities, the exposure group IIhad exposure to melamine but there was no diagnosis of renal abnormalities and the non-exposure group had no exposure to melamine. The exposure II and non-exposure groups were matched with those of exposure group I by birthplaces, gender and date of birth ( ± 3 months). Kidney function tests (urea nitrogen, serum creatinine, uric acid, serum albumin, β2-microglobulin and cystatin C), liver function tests (alanine aminotransferase and aspartate aminotransferase), growth and development assessment and urinary system ultrasonography were implemented between November 2011 and June 2012. The analysis of covariance (least significant difference method) was performed to compare the differences of relevant variables among three groups. The urinary system ultrasonography showed that all abnormalities disappeared in exposure group I and all infants of another two groups had normal ultrasonography. There were statistically significant differences in serum uric acid and albumin of kidney function in exposure group I, exposure group II and non-exposure group ((344 ± 75) and (338 ± 98) and (282 ± 69) µmol/L , (47 ± 5) and (47 ± 6) and (43 ± 5) g/L, all P < 0.05) among three groups. However the differences in the remaining markers of kidney function, markers of liver function and Z scores of weight-for-age and height-for age were all statistically insignificant (all P > 0.05). Further pair-wise comparisons showed that the levels of serum uric acid and albumin in exposure group I were higher than those in non-exposure group (P = 0.001 and 0.010). And the levels of serum uric acid and albumin in exposure group II were also higher than those in non-exposure group (P = 0.003 and 0.005). All affected infants have recovered from kidney abnormalities. Early infant exposure to melamine-contaminated milk formula appears to have no obvious impact on liver function and growth. But its potential impact on kidney function should be further assessed.

IV. HEMOGLOBIN INJECTIONS AND CONSERVATION OF PIGMENT BY KIDNEY, LIVER AND SPLEEN

PubMed Central

Newman, William V.; Whipple, George H.

1932-01-01

When the minimal renal threshold for blood hemoglobin is exceeded there is observed a deposit of iron staining pigment in the epithelium of the renal convoluted tubules. At a certain point this epithelium cannot take up more hemoglobin and this coincides with the minimal renal threshold level. When the injections of blood hemoglobin are kept below the minimal renal threshold level we note a complete absence of iron staining pigment in the renal tubular epithelium. Given a deposit of iron staining pigment in the tubular epithelium, it will slowly disappear during rest periods with no hemoglobin injections. Anemia due to bleeding will accelerate this removal of pigment from the renal epithelium and this indicates a conservation of material by the kidney for use in construction of new hemoglobin. Pigment giving a positive stain for iron will be found in the liver and spleen when hemoglobin injections are given, regardless of the renal threshold. Removal of this pigment is accelerated by anemia due to bleeding and as a rule an anemia period of 2 months at a level of 1/3 normal (40 to 50 per cent hemoglobin) will render the spleen, liver and kidney free from iron staining pigment. Pigment giving a positive iron stain is frequently observed in the mesenteric and lower retroperitoneal lymph glands. This is merely a drainage of pigment and phagocytes including pigment from some organ in which the pigment deposit was primary. In stock dogs in this laboratory the hemoglobin level is quite high when the animals are in a perfectly normal state. The blood hemoglobin averages 120 to 150 per cent hemoglobin. In such dogs iron staining pigment in the spleen is a common finding and on occasion is observed in the liver. To establish an accurate base line for the study of iron and iron staining pigment storage due to diet intake one must submit these dogs to a preliminary anemia period of at least 2 months. Muscle hemoglobin has a very low renal threshold and escapes freely into the urine when given intravenously. Contrasting with blood hemoglobin this musde hemoglobin under identical conditions does not cause the deposit of iron staining pigment within the epithelium of the renal tubules. A pigment giving no iron staining reaction may be found in the epithelium of the convoluted tubules of the kidney. Whether this is due to dietary or other factors is uncertain but this indicates pigment conservation by the kidney. Finally we would emphasize again the fact that the kidney is of considerable importance in the conservation of hemoglobin and hemoglobin split products which presumably are utilized to build up new hemoglobin. PMID:19870019

Breast cancer metastatic to the kidney with renal vein involvement.

PubMed

Nasu, Hatsuko; Miura, Katsutoshi; Baba, Megumi; Nagata, Masao; Yoshida, Masayuki; Ogura, Hiroyuki; Takehara, Yasuo; Sakahara, Harumi

2015-02-01

The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

Impact of preoperative chronic renal failure on liver transplantation: a population-based cohort study

PubMed Central

Chung, Peter Chi-Ho; Chen, Hsiu-Pin; Lin, Jr-Rung; Liu, Fu-Chao; Yu, Huang-Ping

2016-01-01

Purpose The purpose of this study was to assess whether preoperative chronic renal failure (CRF) affects the rates of postoperative complications and survival after liver transplantation. Methods This population-based retrospective cohort study included 2,931 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. Patients were divided into two groups, based on the presence or absence of preoperative CRF. Results The overall estimated survival rate of liver transplantation recipients (LTRs) with preoperative CRF was significantly lower than that of patients without preoperative CRF (P=0.0085). There was no significant difference between the groups in terms of duration of intensive care unit stay, total hospital stay, bacteremia, postoperative bleeding, and pneumonia during hospitalization. Long-term adverse effects, including cerebrovascular disease and coronary heart disease, were not different between patients with versus without CRF. Conclusion These findings suggest that LTRs with preoperative CRF have a higher rate of mortality. PMID:28008264

Clinical spectrum of primary hyperoxaluria type 1: Experience of a tertiary center

PubMed Central

Soliman, Neveen A.; Nabhan, Marwa M.; Abdelrahman, Safaa M.; Abdelaziz, Hanan; Helmy, Rasha; Ghanim, Khaled; Bazaraa, Hafez M.; Badr, Ahmed M.; Tolba, Omar A.; Kotb, Magd A.; Eweeda, Khaled M.; Fayez, Alaa

2018-01-01

Background and aim Primary hyperoxalurias are rare inborn errors of metabolism resulting in increased endogenous production of oxalate that leads to excessive urinary oxalate excretion. Diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. We characterized the clinical presentation as well as renal and extrarenal phenotypes in PH1 patients. Methods This descriptive cohort study included patients with presumable PH1 presenting with nephrolithiasis and/or nephrocalcinosis (NC). Precise clinical characterization of renal phenotype as well as systemic involvement is reported. AGXT mutational analysis was performed to confirm the diagnosis of PH1. Results The study cohort included 26 patients with presumable PH1 with male to female ratio of 1.4:1. The median age at time of diagnosis was 6 years, nevertheless the median age at initial symptoms was 3 years. Thirteen patients (50%) were diagnosed before the age of 5 years. Two patients had no symptoms and were diagnosed while screening siblings of index patients. Seventeen patients (65.4%) had reached end-stage renal disease (ESRD): 6/17 (35.3%) during infancy, 4/17 (23.5%) in early childhood and 7/17 (41.29%) in late childhood. Two patients (7.7%) had clinically manifest extra renal (retina, heart, bone, soft tissue) involvement. Mutational analysis of AGXT gene confirmed the diagnosis of PH1 in 15 out of 19 patients (79%) where analysis had been performed. Fifty percent of patients with maintained renal functions had projected 10 years renal survival. Conclusion PH1 is a heterogeneous disease with wide spectrum of clinical, imaging and functional presentation. More than two-thirds of patients presented prior to the age of 5 years; half of them with the stormy course of infantile PH1. ESRD was the commonest presenting manifestation in two-thirds of our cohort. PMID:28161266

Acute mercury exposition of virgin, pregnant, and lactating rats: Histopathological kidney and liver evaluations.

PubMed

Oliveira, Vitor Antunes; Favero, Gaia; Stacchiotti, Alessandra; Giugno, Lorena; Buffoli, Barbara; de Oliveira, Claudia Sirlene; Lavazza, Antonio; Albanese, Massimo; Rodella, Luigi Fabrizio; Pereira, Maria Ester; Rezzani, Rita

2017-05-01

This work investigated the effects of mercury chloride (HgCl 2 ) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18 th gestation day) and lactating (7 th lactation day) were injected once with HgCl 2 (5 mg/kg) or saline (controls). We observed that HgCl 2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl 2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl 2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl 2 -exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl 2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500-1512, 2017. © 2016 Wiley Periodicals, Inc.

The first clinical liver transplantation of Brazil revisited.

PubMed

Bacchella, T; Machado, M C C

2004-05-01

The first clinical orthotopic liver transplantation in Brazil was performed on August 5, 1968. The patient was awake after surgery and died on the seventh postoperative day due to subdural hematoma, bronchopneumonia, renal failure, and graft rejection. The report of this case is important to understand the evolution of clinical liver transplantation in Brazil, where this procedure is now routinely carried out in many medical centers.

l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

PubMed

Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

2017-01-01

We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Circuit lifespan during continuous renal replacement therapy for combined liver and kidney failure.

PubMed

Chua, Horng-Ruey; Baldwin, Ian; Bailey, Michael; Subramaniam, Ashwin; Bellomo, Rinaldo

2012-12-01

To evaluate circuit lifespan (CL) and bleeding risk during continuous renal replacement therapy (CRRT), in combined liver and renal failure. Single-center retrospective analysis of adults with acute liver failure or decompensated cirrhosis who received CRRT, without anticoagulation or with heparinization in intensive care unit. Seventy-one patients with 539 CRRT circuits were evaluated. Median overall CL was 9 (6-16) hours. CL was 12 (7-24) hours in 51 patients never anticoagulated for CRRT. In 20 patients who subsequently received heparinization, CL was 7 (5-11) hours without anticoagulation, which did not improve with systemic or regional heparinization (P = .231), despite higher peri-circuit activated partial thromboplastin time (APTT) and heparin dose. Using multivariate linear regression, patients with higher baseline APTT or serum bilirubin, or who were not mechanically ventilated, had longer CL (P < .05). Additionally, peri-circuit thrombocytopenia (P < .0001) or higher international normalized ratio (P < .05) predicted longer CL. Of 71 patients, 33 had significant bleeding events. Using multivariate logistic regression, patients with higher baseline APTT, vasoactive drug use >24 hours, or thrombocytopenia, had more bleeding complications (P < .05). Decreasing platelet counts (especially <50 × 10(9)/mm(3)) had an incremental effect on CL (P < .0001). CRRT CL is short in patients with liver failure despite apparent coagulopathy. Thrombocytopenia predicts longer CL and bleeding complications. Copyright © 2012 Elsevier Inc. All rights reserved.

The Intersection of Pulmonary Hypertension and Solid Organ Transplantation.

PubMed

Frost, Adaani E

2016-01-01

Pulmonary hypertension (PH) is a complication and marker of disease severity in many parenchymal lung diseases. It also is a frequent complication of portal hypertension and negatively impacts survival with liver transplant. Pulmonary hypertension is frequently diagnosed in patients with end-stage renal disease who are undergoing dialysis, and it has recently been demonstrated to adversely affect posttransplant outcome in this patient population even though the mechanism of PH is substantially different from that associated with liver disease. The presence of PH in patients with heart failure is frequent, and the necessity for PH therapy prior to heart transplant has evolved in the last decade. We review the frequency of and risk factors for PH in recipients of and candidates for lung, liver, heart, and renal transplants as well as the impact of this diagnosis on posttransplant outcomes.

Safety of statins.

PubMed

Brown, William Virgil

2008-12-01

To examine the evidence for the adverse effects that have been reported during the use of statins. We now have over twenty years of prescription use and many large well controlled trials with statin therapy for hypercholesterolemia. There is only one significant and well documented adverse effect with this group of drugs, rhabdomyolysis. Significant muscle damage is very rare when statin therapy is used in patients carefully screened for concomitant use of other drugs which may interfere with statin catabolism and excretion. Patients with severely impaired liver function are also at risk due to the importance of hepatic excretion of all statins. Chronic myalgias or other pain syndromes have not been confirmed by blinded placebo controlled trials. A significant and reproducible rise in liver enzymes (alanine and aspartate aminotransferases) is observed in 1 to 3% of patients but actual liver damage may not occur at all. Benign and transient proteinuria occurs without evidence of altered renal function. Creatinine clearance is usually increased by statins. Peripheral neuropathy may be a rare adverse effect and this needs further study. Statins are very effective at reducing the incidence of myocardial infarction, stroke and other manifestations of vascular disease. The adverse event rates are very uncommon and the benefit risk ratio is extremely high.

In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates

PubMed Central

Medarova, Zdravka; Vallabhajosyula, Prashanth; Tena, Aseda; Evgenov, Natalia; Pantazopoulos, Pamela; Tchipashvili, Vaja; Weir, Gordon; Sachs, David; Moore, Anna

2009-01-01

Objective As islet transplantation begins to show promise clinically, there is a critical need for reliable, non-invasive techniques to monitor islet graft survival. Previous work in our laboratory has shown that human islets labeled with a superparamagnetic iron oxide contrast agent and transplanted into mice could be detected by magnetic resonance imaging (MRI). The potential translation of these findings to the clinical situation requires validation of our methodology in a non-human primate model, which we have now carried out in baboons (Papio hamadryas) and reported here. Research Design and Methods: For islet labeling, we adapted the FDA-approved superparamagnetic iron oxide contrast agent, Feridex, which is used clinically for liver imaging. After partial pancreatectomy, Feridex-labeled islets were prepared and autotransplanted underneath the renal capsule and into the liver. Longitudinal in vivo MRI at days 1, 3, 8, 16, 23, and 30 after transplantation was performed in order to track the islet grafts. Results The renal subcapsular islet graft was easily detectable on T2*-weighted MRI images as a pocket of signal loss disrupting the contour of the kidney at the transplantation site. Islets transplanted in the liver appeared as distinct signal voids dispersed throughout the liver parenchyma. A semi-automated computational analysis of our MR imaging data established the feasibility of monitoring both the renal and intrahepatic grafts during the studied post-transplantation period. Conclusion This study establishes a method for the noninvasive, longitudinal detection of pancreatic islets transplanted into non-human primates using a low field clinical MRI system. PMID:19502957

A retrospective 15-year review: survival advantage after switching to sirolimus in hepatitis C virus infected liver graft recipients.

PubMed

Shah, M; Shankar, A; Gee, I; Nash, K; Hoare, M; Gibbs, P; Davies, S; Alexander, G J M

2015-02-01

The use of sirolimus-based immune suppression in liver transplantation, particularly in hepatitis C virus (HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards hepatic fibrosis, is renal sparing and may be of benefit in preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus has not been adopted by many transplant centres because of persistent concerns regarding an increased risk of hepatic artery thrombosis, graft loss and death with de novo sirolimus. To review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis. A retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15 years. 113 patients were switched from calcineurin inhibitor (CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15 months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%). Patients switched to sirolimus had improved survival (P < 0.001) and slower progression to cirrhosis (P = 0.001). In patients with HCC (n = 91), sirolimus duration rather than strategy was an independent predictor of survival (P = 0.001) and extended time to HCC recurrence (33 vs. 16 months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108 μmol/L, P = 0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes (P = 0.03). These data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome. © 2014 John Wiley & Sons Ltd.

Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis.

PubMed

Markwardt, Daniel; Holdt, Lesca; Steib, Christian; Benesic, Andreas; Bendtsen, Flemming; Bernardi, Mauro; Moreau, Richard; Teupser, Daniel; Wendon, Julia; Nevens, Frederik; Trebicka, Jonel; Garcia, Elisabet; Pavesi, Marco; Arroyo, Vicente; Gerbes, Alexander L

2017-10-01

The development of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated with high mortality rates. Renal failure is the most significant organ dysfunction that occurs in ACLF. So far there are no biomarkers predicting ACLF. We investigated whether cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) can predict development of renal dysfunction (RD), hepatorenal syndrome (HRS), ACLF, and mortality. We determined the plasma levels of CysC and NGAL in 429 patients hospitalized for acute decompensation of cirrhosis in the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study. The patients were followed for 90 days. Patients without RD or ACLF at inclusion but with development of either had significantly higher baseline concentrations of CysC and NGAL compared to patients without. CysC, but not NGAL, was found to be predictive of RD (odds ratio, 9.4; 95% confidence interval [CI], 1.8-49.7), HRS (odds ratio, 4.2; 95% CI, 1.2-14.8), and ACLF (odds ratio, 5.9; 95% CI, 1.3-25.9). CysC at day 3 was not found to be a better predictor than baseline CysC. CysC and NGAL were both predictive of 90-day mortality, with hazard ratios for CysC of 3.1 (95% CI, 2.1-4.7) and for NGAL of 1.9 (95% CI, 1.5-2.4). Baseline CysC is a biomarker of RD, HRS, and ACLF and an independent predictor of mortality in patients with acutely decompensated liver cirrhosis, though determining CysC at day 3 did not provide any benefit; while NGAL is also associated with short-term mortality, it fails to predict development of RD, HRS, and ACLF. Baseline CysC may help to identify patients at risk earlier and improve clinical management. (Hepatology 2017;66:1232-1241). © 2017 by the American Association for the Study of Liver Diseases.

Roles of renal ammonia metabolism other than in acid-base homeostasis.

PubMed

Weiner, I David

2017-06-01

The importance of renal ammonia metabolism in acid-base homeostasis is well known. However, the effects of renal ammonia metabolism other than in acid-base homeostasis are not as widely recognized. First, ammonia differs from almost all other solutes in the urine in that it does not result from arterial delivery. Instead, ammonia is produced by the kidney, and only a portion of the ammonia produced is excreted in the urine, with the remainder returned to the systemic circulation through the renal veins. In normal individuals, systemic ammonia addition is metabolized efficiently by the liver, but in patients with either acute or chronic liver disease, conditions that increase the addition of ammonia of renal origin to the systemic circulation can result in precipitation and/or worsening of hyperammonemia. Second, ammonia appears to serve as an intrarenal paracrine signaling molecule. Hypokalemia increases proximal tubule ammonia production and secretion as well as reabsorption in the thick ascending limb of the loop of Henle, thereby increasing delivery to the renal interstitium and the collecting duct. In the collecting duct, ammonia decreases potassium secretion and stimulates potassium reabsorption, thereby decreasing urinary potassium excretion and enabling feedback correction of the initiating hypokalemia. Finally, the stimulation of renal ammonia metabolism by hypokalemia may contribute to the development of metabolic alkalosis, which in turn can stimulate NaCl reabsorption and contribute to the intravascular volume expansion, increased blood pressure and diuretic resistance that can develop with hypokalemia. The evidence supporting these novel non-acid-base roles of renal ammonia metabolism is discussed in this review.

Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo.

PubMed

Edison, Erica E; Brosnan, Margaret E; Meyer, Christian; Brosnan, John T

2007-12-01

A fraction of the body's creatine and creatine phosphate spontaneously degrades to creatinine, which is excreted by the kidneys. In humans, this amounts to approximately 1-2 g/day and demands a comparable rate of de novo creatine synthesis. This is a two-step process in which l-arginine:glycine amidinotransferase (AGAT) catalyzes the conversion of glycine and arginine to ornithine and guanidinoacetate (GAA); guanidinoacetate methyltransferase (GAMT) then catalyzes the S-adenosylmethionine-dependent methylation of GAA to creatine. AGAT is found in the kidney and GAMT in the liver, which implies an interorgan movement of GAA from the kidney to the liver. We studied the renal production of this metabolite in both rats and humans. In control rats, [GAA] was 5.9 microM in arterial plasma and 10.9 microM in renal venous plasma for a renal arteriovenous (A-V) difference of -5.0 microM. In the rat, infusion of arginine or citrulline markedly increased renal GAA production but infusion of glycine did not. Rats fed 0.4% creatine in their diet had decreased renal AGAT activity and mRNA, an arterial plasma [GAA] of 1.5 microM, and a decreased renal A-V difference for GAA of -0.9 microM. In humans, [GAA] was 2.4 microM in arterial plasma, with a renal A-V difference of -1.1 microM. These studies show, for the first time, that GAA is produced by both rat and human kidneys in vivo.

Adult onset Still's disease and collapsing glomerulopathy: successful treatment with intravenous immunoglobulins and mycophenolate mofetil.

PubMed

Bennett, A N; Peterson, P; Sangle, S; Hangartner, R; Abbs, I C; Hughes, G R V; D'Cruz, D P

2004-06-01

In this Grand Round we present a 32-yr-old African man who became severely ill after a 5-month history of weight loss, pyrexia, arthralgia, sweats and rash. He went on to develop pericarditis, pericardial effusion with tamponade, hepatomegaly with abnormal liver function tests, lymphadenopathy, massive proteinuria and required ventilatory, circulatory and renal support. The differential diagnosis was adult onset Still's disease, systemic lupus erythematosus (SLE), infection and lymphoma. Primary infection and lymphoma were excluded and he was treated, with dramatic success, with intravenous immunoglobulins (i.v.IG). Subsequent renal biopsy excluded SLE but confirmed collapsing glomerulopathy. The proteinuria improved dramatically following treatment with mycophenolate mofetil. We discuss some of the difficult diagnostic and management issues raised by this patient and the different uses and mechanisms of action of i.v.IG.

Benefit of early inflow exclusion during living donor liver transplantation for unresectable hepatoblastoma.

PubMed

Uchida, Hajime; Fukuda, Akinari; Sasaki, Kengo; Hirata, Yoshihiro; Shigeta, Takanobu; Kanazawa, Hiroyuki; Nakazawa, Atsuko; Miyazaki, Osamu; Nosaka, Shunsuke; Mali, Vidyadhar Padmakar; Sakamoto, Seisuke; Kasahara, Mureo

2016-11-01

Hepatoblastoma (HB) is a highly malignant primary liver tumor in children. Although liver transplantation (LT) is an effective treatment for unresectable HB with good long-term outcomes, post-transplant survival is mainly affected by recurrence, despite adjuvant chemotherapy. Novel strategies are needed to improve the outcomes in patients undergoing LT for unresectable HB. Twelve children received LT for unresectable HB. In 9 patients, we applied early exclusion of hepatic inflow (hepatic artery and portal vein) and creation of a temporary portocaval shunt during LT. There were differences in the duration of and the blood loss during operation as compared with previously reports. The estimated glomerular filtration rate was well preserved at 3, 6, and 12months and the latest follow-up after LT, and the recurrence-free survival was 88.9%. Early inflow control during LT for unresectable HB may benefit recurrence-free survival by minimizing blood loss and tumor dissemination, preserving renal function and allowing early adjuvant chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimation of liver parameters and oxidative stress in chronic renal failure patients on hemodialysis in Erbil governorate

NASA Astrophysics Data System (ADS)

Kakey, Musher Ismail Salih; Abdoulrahman, Kamaran Kaiani

2017-09-01

The present study aims to evaluate iron related parameters in chronic renal failure (CRF) patients on hemodialysis (HD). The study was carried out in Kidney Dialysis Center of Hawler Teaching Hospital in Erbil governorate. This study comprised (76) patients with chronic renal failure on hemodialysis and 41 healthy subjects as a control group of same ages. All hemodialysis patients were taking erythropoietin. The blood samples were taken from the patients before and after the process of hemodialysis for liver parameters and oxidative stress estimations. The results of this study showed lower levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin, total protein and total antioxidant capacity (TAC), while higher levels of alkaline phosphatase (ALP), direct bilirubin and malondialdeyhde (MDA) before analysis was seen. Hemodialysis causes increasing in AST, ALT, albumin, total bilirubin, total protein and decreasing in ALP, direct bilirubin MDA and TAC.

Comparison of FDG-PET/CT images between chronic renal failure patients on hemodialysis and controls.

PubMed

Toriihara, Akira; Kitazume, Yoshio; Nishida, Hidenori; Kubota, Kazunori; Nakadate, Masashi; Tateishi, Ukihide

2015-01-01

The whole-body 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) distribution in chronic renal failure (CRF) patients on hemodialysis would be different from that in subjects with normal renal function, because they lack urinary FDG excretion and remain in a constant volume overload. We evaluated the difference in the physiological uptake pattern of FDG between chronic renal failure patients on hemodialysis and control subjects. The subjects for this retrospective study consisted of 24 chronic renal failure patients on hemodialysis (HD group) and 24 age- and sex-matched control subjects (NC group). Standardized uptake values normalized by the body weight (SUVbw), ideal body weight (SUVibw), lean body mass (SUVlbm), and body surface area (SUVbsa) in the cerebellum, lungs, liver, gluteal muscles and subcutaneous fat, spleen, thoracolumbar spine, thoracic and abdominal aorta, and right atrium were calculated in positron emission tomography/computed tomography (PET/CT) images. SUVbw in the gluteal muscles, subcutaneous fat, spleen and right atrium was significantly higher in the HD group as compared to that in the NC group (p < 0.05; unpaired t test). In addition, SUVibm, SUVlbm, as well as SUVbsa in the abdominal aorta were significantly higher in the HD group as compared to those in the NC group (p < 0.05; unpaired t test). In conclusion, as compared to normal subjects, chronic renal failure patients on hemodialysis show significantly higher physiological FDG uptake in the soft tissues, spleen and blood pool.

Comparison of FDG-PET/CT images between chronic renal failure patients on hemodialysis and controls

PubMed Central

Toriihara, Akira; Kitazume, Yoshio; Nishida, Hidenori; Kubota, Kazunori; Nakadate, Masashi; Tateishi, Ukihide

2015-01-01

The whole-body 2-deoxy-2-[18F]fluoro-D-glucose (FDG) distribution in chronic renal failure (CRF) patients on hemodialysis would be different from that in subjects with normal renal function, because they lack urinary FDG excretion and remain in a constant volume overload. We evaluated the difference in the physiological uptake pattern of FDG between chronic renal failure patients on hemodialysis and control subjects. The subjects for this retrospective study consisted of 24 chronic renal failure patients on hemodialysis (HD group) and 24 age- and sex-matched control subjects (NC group). Standardized uptake values normalized by the body weight (SUVbw), ideal body weight (SUVibw), lean body mass (SUVlbm), and body surface area (SUVbsa) in the cerebellum, lungs, liver, gluteal muscles and subcutaneous fat, spleen, thoracolumbar spine, thoracic and abdominal aorta, and right atrium were calculated in positron emission tomography/computed tomography (PET/CT) images. SUVbw in the gluteal muscles, subcutaneous fat, spleen and right atrium was significantly higher in the HD group as compared to that in the NC group (p < 0.05; unpaired t test). In addition, SUVibm, SUVlbm, as well as SUVbsa in the abdominal aorta were significantly higher in the HD group as compared to those in the NC group (p < 0.05; unpaired t test). In conclusion, as compared to normal subjects, chronic renal failure patients on hemodialysis show significantly higher physiological FDG uptake in the soft tissues, spleen and blood pool. PMID:25973341

The Effect of Chronic Renal Failure on Drug Metabolism and Transport

PubMed Central

Dreisbach, Albert W; Lertora, Juan JL

2009-01-01

Background Chronic renal failure (CRF) has been shown to significantly reduce the nonrenal clearance and alter bioavailability of drugs predominantly metabolized by the liver and intestine. Objectives The purpose of this article is to review all significant animal and clinical studies dealing with the effect of CRF on drug metabolism and transport. Methods The National Library of Medicine PubMed was utilized with the search terms ‘chronic renal failure, cytochrome P450, liver metabolism, efflux drug transport and uptake transport’ including relevant articles back to 1969. Results Animal studies in CRF have shown a major downregulation (40-85%) of hepatic and intestinal cytochrome P450 (CYP) metabolism. High levels of parathyroid hormone, cytokines, and uremic toxins have been shown to reduce CYP activity. Phase II reactions and drug transporters such as P-glycoprotein (Pgp) and organic anion transporting polypeptide (OATP) are also affected. Conclusion CRF alters intestinal, renal, and hepatic drug metabolism and transport producing a clinically significant impact on drug disposition and increasing the risk for adverse drug reactions. PMID:18680441

The utility of liver function tests for mortality prediction within one year in primary care using the algorithm for liver function investigations (ALFI).

PubMed

McLernon, David J; Dillon, John F; Sullivan, Frank M; Roderick, Paul; Rosenberg, William M; Ryder, Stephen D; Donnan, Peter T

2012-01-01

Although liver function tests (LFTs) are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease. In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic) and performance, and validated using a separate cohort of Scottish primary care practices. From the derivation cohort (n = 95 977), 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase). The C-statistic for the final model was 0.82 (95% CI 0.80-0.84), and was similar in the validation cohort (n = 11 653) 0.86 (0.79-0.90). As an example of performance, for a 10% predicted probability cut-off, sensitivity = 52.8%, specificity = 94.0%, PPV = 21.0%, NPV = 98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%. The Algorithm for Liver Function Investigations (ALFI) is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the clinical utility of ALFI remains to be established since LFTs did not improve an already high NPV for short term mortality and only modestly improved a very low PPV.

Toxicity following methoxyflurane anaesthesia. IV. The role of obesity and the effect of low dose anaesthesia on fluoride metabolism and renal function.

PubMed

Samuelson, P N; Merin, R G; Taves, D R; Freeman, R B; Calimlim, J F; Kumazawa, T

1976-09-01

Seven obese and five normal weight patients were studied before, during and after one hour of methoxyflurane-nitrous oxide anaesthesia during peripheral surgical operations and compared with eight patients of normal weight anaesthetized with nitrous oxide-meperidine and d-tubocurare. Estimates were made of renal function, including serum and urinary electrolytes, osmolarity, uric acid, urea and creatinine. Renal clearances for the latter three substances were also calculated. Serum and urinary inorganic and organic fluoride concentrations were measured, as were renal clearances. This low dose methoxyflurane anaesthesia resulted only in a decrease in uric acid clearance among all the measures, when compared to the meperidine-nitrous oxide controls. The clearance of uric acid remained depressed for longer in the obese patients, but otherwise they did not differ from the normal weight patients. It is possible but not proven that depressed uric acid clearance may be related to the organic fluoride metabolite and an early indicator of methoxyflurane renal toxicity. The previously documented biotransformation of methoxyflurane was seen in this study. A double peak in serum inorganic fluoride was shown in all patients but one. Rather large differences in peak levels of serum inorganic fluoride occurred. The only significant difference between the obese and normal weight patients as far as fluoride metabolism was concerned was a greater variability in the serum inorganic fluoride levels in the obese patients. It would appear that the obese patient metabolizes methoxyflurane in a quantitatively if not qualitatively different fashion than the normal weight patient, perhaps because of fatty infiltration of the liver. Caution is advised in the use of methoxyflurane for more than 90 minutes of low concentration administration in view of the unpredictability of the biotransformation.

Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice.

PubMed

Jia, Yingli; He, Jinzhao; Wang, Liang; Su, Limin; Lei, Lei; Huang, Wei; Geng, Xiaoqiang; Zhang, Shun; Meng, Xiaolu; Zhou, Hong; Yang, Baoxue

2018-01-01

A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson's trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

The apelin-APJ axis: A novel potential therapeutic target for organ fibrosis.

PubMed

Huang, Shifang; Chen, Linxi; Lu, Liqun; Li, Lanfang

2016-05-01

Apelin, an endogenous ligand of the G-protein-coupled receptor APJ, is expressed in a diverse number of organs. The apelin-APJ axis helps to control the processes of pathological and physiological fibrosis, including renal fibrosis, cardiac fibrosis, liver fibrosis and pulmonary fibrosis. However, the role of apelin-APJ in organ fibrosis remains controversial due to conflicting study results. The apelin-APJ axis is a detrimental mechanism which promotes liver fibrosis mainly via up-regulation the expression of collagen-II and platelet-derived growth factor receptor β (PDGFRβ). On the contrary, the apelin-APJ axis is beneficial for renal fibrosis, cardiac fibrosis and pulmonary fibrosis. The apelin-APJ axis alleviates renal fibrosis by restraining the expression of transforming growth factor-β1 (TGF-β1). In addition, the apelin-APJ axis attenuates cardiac fibrosis through multiple pathways. Furthermore, the apelin-APJ axis has beneficial effects on experimental bronchopulmonary dysplasia (BPD) and acute respiratory distress syndrome (ARDS) which suggest the apelin-APJ axis potentially alleviates pulmonary fibrosis. In this article, we review the controversies associated with apelin-APJ in organ fibrosis and introduce the drugs that target apelin-APJ. We conclude that future studies should place more emphasis on the relationship among apelin isoforms, APJ receptor subtypes and organ fibrosis. The apelin-APJ axis will be a potential therapeutic target and those drugs targeted for apelin-APJ may constitute a novel therapeutic strategy for renal fibrosis, cardiac fibrosis, liver fibrosis and pulmonary fibrosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Preemptive living-donor kidney transplantation: clinical course and outcome.

PubMed

el-Agroudy, Amgad E; Donia, Ahmed F; Bakr, Mohamed A; Foda, Mohamed A; Ghoneim, Mohamed A

2004-05-15

Dialysis is not only associated with morbidity, it is also expensive. In developing countries, preemptive renal transplantation (Tx) may be a cost-effective option, offering an additional benefit to conventional renal Tx. Between March 1976 and March 2001, 1,279 first living-donor Txs were performed in our center. The 82 patients (6.4%) who underwent Tx without prior dialysis were compared with 1,197 patients who had been dialyzed before Tx. The dialysis-dependent group received more blood transfusions (65% vs. 30%) before Tx. Actuarial graft and patient survival at 5 years was comparable in both groups (P =0.2 and P =0.8, respectively). The incidence of acute and chronic rejection was not different between the two groups. Mortality rate was also similar in the two groups. The main cause of death with a functioning graft was cardiovascular in the preemptive Tx group and chronic liver disease and infection in the control group. In the context of a developing country, preemptive Tx offers comparable patient and graft survival to conventional renal Tx and eliminates the complications, inconvenience, and cost of dialysis.

Tissue heavy metal concentrations of stranded California sea lions (Zalophus californianus) in Southern California.

PubMed

Harper, Erin R; St Leger, Judy A; Westberg, Jody A; Mazzaro, Lisa; Schmitt, Todd; Reidarson, Tom H; Tucker, Melinda; Cross, Dee H; Puschner, Birgit

2007-06-01

Concentrations of nine heavy metals (As, Cd, Cu, Fe, Hg, Pb, Mn, Mo and Zn) were determined in the hepatic and renal tissues of 80 stranded California sea lions (Zalophus californianus). Significant age-dependant increases were observed in liver and kidney concentrations of cadmium and mercury, and renal zinc concentrations. Hepatic iron concentrations were significantly higher in females than males. Animals with suspected domoic acid associated pathological findings had significantly higher concentrations of liver and kidney cadmium; and significantly higher liver mercury concentrations when compared to animals classified with infectious disease or traumatic mortality. Significantly higher hepatic burdens of molybdenum and zinc were found in animals that died from infectious diseases. This is the largest study of tissue heavy metal concentrations in California sea lions to date. These data demonstrate how passive monitoring of stranded animals can provide insight into environmental impacts on marine mammals.

Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases.

PubMed

Han, Eugene; Lee, Yong Ho

2017-12-01

As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged. Copyright © 2017 Korean Diabetes Association.

[Osteomyelitis and papillary renal adenoma in a red panda (Ailurus fulgens fulgens)].

PubMed

Kummerfeld, M; Knieriem, A; Wohlsein, P

2008-11-01

A 13 year-old female Red Panda (Ailurus fulgens fulgens) kept in a zoological garden was euthanatized due to poor general condition. Pathological examination revealed a chronic bacterial ulcerative to necrotizing dermatitis and osteomyelitis at the lower jaw with subsequent pyogranulomatous pneumonia and diffuse hydropic degeneration of the liver. Additionally, in the kidney a papillary renal adenoma was found. Immunohistochemistry revealed an expression of cytokeratins 8 and/or 19 indicating an origin from the renal tubular epithelium.

[Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

PubMed

Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A

2012-01-01

Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

Protective role of dietary Spirulina platensis against diazinon-induced Oxidative damage in Nile tilapia; Oreochromis niloticus.

PubMed

Abdelkhalek, Nevien K M; Eissa, Ismail A M; Ahmed, Eman; Kilany, Omnia E; El-Adl, Mohamed; Dawood, Mahmoud A O; Hassan, Ahmed M; Abdel-Daim, Mohamed M

2017-09-01

The current study was performed to investigate the ameliorating effect of dietary supplementation of 0.5 and 1% Spiurolina platensis (SP) diet against the sub-acute toxicity of diazinon (DZN) 0.28mg/L in Nile tilapia. At the end of experiment after 28days, hepatic and renal damage markers (aspartate transaminase, alanine transaminase, alkaline phosphatase, urea, uric acid and creatinine), serum biochemical parameters (total proteins, albumin, cholesterol and glucose) and tissue antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and malondialdehyde) were detesrmined. The results of the current study revealed significant improvement in hepatic and renal damage markers after SP supplementation in fish exposed to DZN toxicity. Moreover, SP improved serum biochemical markers through increasing serum albumin and globulins with a significant decrease in serum glucose and cholesterol. In addition, liver, kidneys and gills antioxidant status showed a significant improvement after SP supplemented to fish exposed to DZN where a significant increase in tissue antioxidant activity were observed with a significant decline in lipid peroxidation levels. It can be concluded that, SP supplementation attenuated the toxic effect of DZN toxicity in Nile tilapia through improving liver and kidney functions with a significant enhancement of tissue antioxidant status. Copyright © 2017 Elsevier B.V. All rights reserved.

[From gene to disease; primary hyperoxaluria type I caused by mutations in the AGXT gene].

PubMed

van Woerden, C S; Groothof, J W; Wanders, R J A; Waterham, H R; Wijburg, F R

2006-07-29

Primary hyperoxaluria type I (PH1) is a congenital defect in glyoxylate metabolism caused by a deficiency in the liver-specific peroxisomal enzyme known as alanine glyoxylate aminotransferase (AGT). The deficiency is due to mutations in the AGXT gene, located on chromosome 2q37.3, and results in the conversion of glyoxylate to oxalate. The crystallisation of oxalate with calcium results in symptoms varying from a solitary kidney stone to end-stage renal disease with systemic oxalosis. The diagnosis is based on increased oxalate and glycolate excretion in the urine, reduced AGT activity in liver tissue, and confirmed mutations in the AGXT gene. Over 50 disease-causing mutations have been identified in PH1, which are associated with a wide range of effects on the AGT enzyme. Homozygous Gly170Arg or Phei52Ile mutations are associated with a reduction in urinary oxalate excretion upon pyridoxine administration and long-term preservation of renal function when treatment is initiated in a timely manner. Homozygous 33insC and Gly82Arg mutations result in a much poorer prognosis. Mutational analysis of the AGXT gene in PH1 patients can be a useful tool for establishing the diagnosis and choosing an appropriate therapeutic strategy.

Nonalcoholic fatty liver disease (NAFLD)--is it a new marker of hyporesponsiveness to recombinant human erythropoietin in patients that are on chronic hemodialysis?

PubMed

Orlic, L; Mikolasevic, I; Lukenda, V; Racki, S; Stimac, D; Milic, S

2014-12-01

Anemia is a major consequence of chronic kidney disease (CKD) that develops early in the course of illness and affects most patients who exhibit some degree of reduced renal function. Erythropoietin (EPO) deficiency is considered the most important cause of anemia in CKD. Renal anemia has serious clinical consequence. In addition to reducing patient physical capacity and quality of life, anemia induces adaptive cardiovascular mechanisms that increase the risk of cardiovascular disease and death. Thus, treatment of anemia in CKD is very important. While EPO is effective in correcting anemia in most cases, up to 10% of patients however, have an inadequate response to therapy. The two most common and important reasons why patients become relatively unresponsive to EPO therapy are the development of true iron deficiency and the onset of an inflammatory state that impairs the response to EPO. Indeed, the role of inflammation and pro-inflammatory cytokines in resistance to EPO therapy is gaining increasing recognition. On the other hand, the main organ for C-reactive protein (CRP) synthesis is the liver and it is well known that the synthesis of an acute-phase proteins by the liver is up regulated by inflammation. The main consequence of nonalcoholic fatty liver disease (NAFLD) is sub-chronic liver inflammation that leads and contributes to dyslipidemia, inflammation, enhanced oxidative stress and endothelial dysfunction. Considering the recent data about high prevalence of NAFLD in CKD patients, probably due to shared metabolic risk factors, we hypothesized that end-stage renal disease (ESRD) patients with NAFLD will need a much higher dose of EPO to achieve the target hemoglobin levels in comparison with ESRD patients without NAFLD. The possible underlying mechanism is sub-chronic liver inflammation in NAFLD patients that leads and contributes to poor response to EPO. Therefore, we believe that NAFLD could be a new clinical marker of poor response to EPO therapy in ESRD patients. Optimizing response to EPO therapy is important for both patient outcomes and the cost of treatment, and require consideration of a growing number of factors. Detection of NAFLD by some of non-invasive methods in ESRD patients could identify responsiveness and resistance to EPO therapy. Furthermore, we propose that all the patients who undergo dialysis treatment should be screened for NAFLD in order to identify the patients that will have a poor response to EPO therapy. The work could help to determine whether we have a new marker of poor EPO response in ESRD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for Mucormycosis▿

PubMed Central

Spellberg, Brad; Andes, David; Perez, Mario; Anglim, Anne; Bonilla, Hector; Mathisen, Glenn E.; Walsh, Thomas J.; Ibrahim, Ashraf S.

2009-01-01

We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis. PMID:19433555

Acute renal failure in 2 adult llamas after exposure to Oak trees (Quercus spp.)

PubMed Central

Chamorro, Manuel F.; Passler, Thomas; Joiner, Kellye; Poppenga, Robert H.; Bayne, Jenna; Walz, Paul H.

2013-01-01

Two adult llamas (Lama glama) previously exposed to oak trees (Quercus spp.) were presented with a history of depression and anorexia. Clinicopathological abnormalities included severe gastroenteritis, acute renal failure, and increased liver enzymes. This is believed to be the first report of oak toxicosis in South American camelids. PMID:23814303

Discrepant effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on oxidative stress and energy metabolism in the livers and kidneys of mice.

PubMed

Yan, Jin; Wang, Dezhen; Miao, Jiyan; Liu, Chang; Wang, Yao; Teng, Miaomiao; Zhou, Zhiqiang; Zhu, Wentao

2018-08-01

Endosulfan, an organochloride pesticide, has been used for many commercial purposes. Endosulfan is composed of two isomers, α-endosulfan and β-endosulfan. In biological and soil systems, endosulfan is metabolized into endosulfan sulfate. In this study, the different toxicological effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on the livers and kidneys of mice were comprehensively investigated. The results demonstrated that both endosulfan isomers and endosulfan sulfate disturbed the hepatic and renal antioxidant systems. Furthermore, 1 H NMR metabolomics analysis revealed that endogenous metabolites involved in oxidative stress and energy metabolism were altered after exposure to these compounds. In the liver, the changes in hepatic endogenous metabolites and the induction of hepatic CYP450 mRNA isoforms were similar among mice treated with the three compounds, and the sulfate metabolite was the exclusive exogenous compound detected. Therefore, the metabolism of α- and β-endosulfan to endosulfan sulfate is likely the main cause of toxicological effects in the livers of mice. However, in kidneys, the changes in the metabolome and in CYP450 mRNA expression induced by α-endosulfan and β-endosulfan were stereoselective. Additionally, endosulfan sulfate, which induced a significant increase of renal Cyp3a11, showed a more robust disturbance of renal metabolites than either of the two isomers. These findings revealed that more attention should be given to the toxicological evaluation of endosulfan sulfate in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Matcha, a powdered green tea, ameliorates the progression of renal and hepatic damage in type 2 diabetic OLETF rats.

PubMed

Yamabe, Noriko; Kang, Ki Sung; Hur, Jong Moon; Yokozawa, Takako

2009-08-01

Matcha, a powdered green tea produced by grinding with a stone mill, has been popularly used in the traditional tea ceremony and foods in Japan. Matcha is well known to be richer in some nutritional elements and epigallocatechin 3-O-gallate than other green teas. In our previous study, epigallocatechin 3-O-gallate exhibited protective effects against renal damage in a rat model of diabetic nephropathy. In the present study, we investigated the preventive effects of Matcha (50, 100, or 200 mg/kg/day) on the progression of hepatic and renal damage in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats were orally administered Matcha for 16 weeks, and we assessed biochemical parameters in the serum, liver, and kidney and expression levels of major products of advanced glycation end products (AGEs), N(6)-(carboxylmethyl)lysine (CML) and N(6)-(carboxylethyl)lysine (CEL), receptor for AGE (RAGE), and sterol regulatory element binding proteins (SREBPs)-1 and -2. Serum total protein levels were significantly increased by Matcha administration, whereas the serum albumin and glycosylated protein levels as well as the renal glucose and triglyceride levels were only slightly or not at all affected. However, Matcha treatment significantly lowered the glucose, triglyceride, and total cholesterol levels in the serum and liver, renal AGE levels, and the serum thiobarbituric acid-reactive substances levels. In addition, Matcha supplementation resulted in decreases in the renal CML, CEL, and RAGE expressions as well as an increase in hepatic SREBP-2 expression, but not that of SREBP-1. These results suggest that Matcha protects against hepatic and renal damage through the suppression of renal AGE accumulation, by decreases in hepatic glucose, triglyceride, and total cholesterol levels, and by its antioxidant activities.

Cytochrome P450-2C11 mRNA is not expressed in endothelial cells dissected from rat renal arterioles.

PubMed

Heil, Sandra G; De Vriese, An S; Kluijtmans, Leo A J; Dijkman, Henry; van Strien, Denise; Akkers, Robert; Blom, Henk J

2005-01-01

Cytochrome P450 (CYP) isoenzymes (CYP2C and CYP2J) are involved in the production of epoxyeicosatrienoic acids, which are postulated as endothelium-derived hyperpolarizing factors (EDHFs). We hypothesized that if CYP2C11 is involved in the EDHF-mediated responses, its mRNA should be expressed in endothelial cells. We, therefore, examined the mRNA expression of CYP2C11 in endothelial cells of renal arterioles. Laser microdissection was applied to isolate endothelial cells from the renal arterioles of 4 male and 4 female Wistar rats. As a positive control of CYP2C11 expression, hepatocytes were also dissected from these rats. RNA was isolated and real-time quantitative polymerase chain reaction (Q-PCR) analysis was applied. Q-PCR analysis showed that CYP2C11 mRNA was not expressed in laser microdissected endothelial cells of renal arterioles of male and female rats. CYP2C11 mRNA expression was highly abundant in hepatocytes dissected from male livers, but in female livers hardly any CYP2C11 mRNA was detected. We have shown that endothelial cells can be dissected from small renal arterioles by laser microdissection to study the mRNA expression of specific genes by Q-PCR. Using this novel tool, we demonstrated that the CYP2C11 mRNA was not expressed in the endothelial cells of renal arterioles. Therefore, we speculate that CYP2C11 does not contribute to the EDHF-mediated responses in renal arterioles. Copyright (c) 2005 S. Karger AG, Basel.

Potential immunotoxic effects of trichloroethylene-induced IV allergic reaction in renal impairment

PubMed Central

Yu, Jun-Feng; Feng, Yan-Yan

2017-01-01

Trichloroethylene (TCE) is known to induce allergic contact dermatitis and subsequent occupational medicamentosa-like dermatitis (OMLD) with multi-system injuries, including liver, kidney, and skin injuries. However, the mechanisms underlying immune system dysfunction that result in organ injury have not yet been clearly elucidated. In the present study, we measured the levels of secreted cytokines by effect or T cells in TCE-treated guinea pigs to better understand the contribution of allergic disorders in renal injuries. We immunized guinea pigs with trichloroethylene using the Guinea Pig Maximization Test (GPMT) and scored the inflammation on the guinea pigs’ skin. The kidney function and ultra-structural changes in the kidneys were detected using biochemical methods and electron microscopy. The deposition of cytokines was determined using immunohistochemistry. The sensitization rate was 63.16% in the TCE-sensitized groups. The electron microscopy results showed tubular epithelial cell mitochondrial swelling, vacuolar degeneration, and atrophy of the microvillus in the sensitized groups. A high degree of cytokine deposition was observed in the renal tubular proximal epithelial cells in the TCE-sensitized groups. As observed in this study, the variation in the level of immune system activation not only indicates that TCE can largely magnify the immune reaction but also suggests a potential role of immune dysfunction in renal impairment. PMID:28867961

Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects

PubMed Central

Oniki, Kentaro; Saruwatari, Junji; Izuka, Tomoko; Kajiwara, Ayami; Morita, Kazunori; Sakata, Misaki; Otake, Koji; Ogata, Yasuhiro; Nakagawa, Kazuko

2015-01-01

In normal weight subjects (body mass index < 25 kg/m2), non-alcoholic fatty liver disease (NAFLD) is likely to coexist with metabolic diseases. The patatin-like phospholipase 3 (PNPLA3) polymorphism rs738409 (c.444C>G) is associated with the risk of NAFLD and/or renal dysfunction; however, the influence of the weight status on the associations remains unknown. We aimed to clarify the associations of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while also paying careful attention to the weight status of the subjects. Cross-sectional and retrospective longitudinal studies with 5.5 ± 1.1 years of follow-up were conducted in 740 and 393 Japanese participants (61.2 ± 10.5 and 67.5 ± 6.0 years), respectively, during a health screening program. Among 591 subjects who did not have a habitual alcohol intake and/or hepatitis B or C virus infections, the PNPLA3 G/G genotype was associated with the risk for NAFLD in normal weight subjects [odds ratio (95% CI): 3.06 (1.11–8.43), P < 0.05]. Among all subjects, carriers of the PNPLA3 G/G genotype with a normal weight had a lower eGFR than those of the C/C genotype [partial regression coefficient (SE): -3.26 (1.48), P < 0.05]. These associations were replicated in the longitudinal analyses. Among the overweight subjects, none of the genotypes were significantly associated in the cross-sectional and longitudinal analyses; however, the power of the analyses was small, especially in the analyses among overweight subjects. The findings of this study suggest that carriers of the PNPLA3 G/G genotype with a normal weight status should nevertheless be carefully monitored for the presence of NAFLD and/or renal dysfunction. PMID:26200108

Temporal monitoring of liver and kidney lesions in contaminated East Greenland polar bears (Ursus maritimus) during 1999-2010.

PubMed

Sonne, Christian; Letcher, Robert J; Leifsson, Pall S; Rigét, Frank F; Bechshøft, Thea Ø; Bossi, Rossana; Asmund, Gert; Dietz, Rune

2012-11-01

Organohalogen contaminants bioaccumulate to high concentrations in tissues of polar bears (Ursus maritimus). The exposure levels are in the order to be toxic to inner organs like liver and kidney. We therefore investigated the temporal development of lesions in liver (n=115) and kidney (n=122) samples from East Greenland polar bears taken over the 12 year period from 1999 to 2010. Seven liver and seven kidney lesions were observed of which six were age-related. Controlling for this, the analyses showed that hepatic steatosis and renal cell infiltrations, glomerular sclerosis and tubular hyperplasia decreased over the investigated time period (all p<0.05). Similarly, hypertrophy of hepatic Ito cells, renal glomerular capillary wall thickening and interstitial fibrosis increased over the study period (all p<0.05). Regarding contaminant, concentrations of polybrominated diphenyl ethers in adipose tissue were negatively associated with hepatic mononuclear cell infiltrations (p=0.05) and a similar trend was found for Hg (p=0.09). Hexachlorobenzene was positively associated with portal cell infiltrations and hepatic lipid granulomas, while polychlorinated biphenyls were negatively associated with the prevalence of steatosis (both p<0.05) and a similar trend was found for hexachlorocyclohexanes (p=0.08). Mercury was positively correlated with the frequencies of hypertrophic Ito cells (p=0.002) and a similar trend was found for perfluorooctanesulfonic acid (p=0.07). In renal tissue, hexachlorocyclohexanes were positively associated with medullar hyaline casts (p=0.03) and a similar trend was found for cell infiltrations (p=0.08). There was a trend of trans-nonachlor being positively associated with glomerular sclerosis (p=0.06) while dichlorodiphenyltrichloroethanes were negatively associated with tubular hyperplasia (p=0.02). These results suggest that specific liver and renal lesions have decreased or increased over time and that long-range transported organohalogen contaminants and mercury may be among the co-factors responsible for these observations. These relationships are important to take into account when biomonitoring health and pollution in wildlife species such as polar bears. Copyright © 2012 Elsevier Ltd. All rights reserved.

Correlation between differential renal function estimation using CT-based functional renal parenchymal volume and (99m)Tc - DTPA renal scan.

PubMed

Sarma, Debanga; Barua, Sasanka K; Rajeev, T P; Baruah, Saumar J

2012-10-01

Nuclear renal scan is currently the gold standard imaging study to determine differential renal function. We propose helical CT as single modality for both the anatomical and functional evaluation of kidney with impaired function. In the present study renal parenchymal volume is measured and percent total renal volume is used as a surrogate marker for differential renal function. The objective of this study is to correlate between differential renal function estimation using CT-based renal parenchymal volume measurement with differential renal function estimation using (99m)TC - DTPA renal scan. Twenty-one patients with unilateral obstructive uropathy were enrolled in this prospective comparative study. They were subjected to (99m)Tc - DTPA renal scan and 64 slice helical CT scan which estimates the renal volume depending on the reconstruction of arterial phase images followed by volume rendering and percent renal volume was calculated. Percent renal volume was correlated with percent renal function, as determined by nuclear renal scan using Pearson coefficient. RESULTS AND OBSERVATION: A strong correlation is observed between percent renal volume and percent renal function in obstructed units (r = 0.828, P < 0.001) as well as in nonobstructed units (r = 0.827, P < 0.001). There is a strong correlation between percent renal volume determined by CT scan and percent renal function determined by (99m)TC - DTPA renal scan both in obstructed and in normal units. CT-based percent renal volume can be used as a single radiological tests for both functional and anatomical assessment of impaired renal units.

Effects of prolonged daily low level mercuric chloride dosing in a horse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, M.C.; Seawright, A.A.

1978-12-01

Relatively few of the signs hitherto accepted as being consistent with chronic inorganic mercury intoxication were exhibited by a horse exposed to 31.3 g inorganic mercury (dose rate 0.4 mg/kg) given as mercuric chloride over 23.5 weeks. Clinical features included poor appetite, weight loss, debility, dullness, transient diarrhea and polydipsia, with little impairment of functional renal capacity. Limited degenerative changes were seen in the renal tubules. Edema and a mild inflammatory infiltrate of predominantly the mucosa and submucosa caused marked thickening of the lower alimentary tract. An approximate mean plasma inorganic mercury concentration of 400 ng/ml was quickly reached andmore » maintained. The kidneys had the highest tissue mercury content, almost 10 times greater than the liver and over 70 times that found in the intestinal mucosa and the dorsal root ganglia. 18 references, 6 figures.« less

Durability of small-for-size living donor allografts.

PubMed

Au, Kin Pan; Chan, See Ching; Chok, Kenneth Siu Ho; Chan, Albert Chi Yan; Wong, Tiffany Cho Lam; Sharr, William Wei; Lo, Chung Mau

2015-11-01

Our aim was to study the long-term outcomes of living donor liver transplantation using small-for-size (SFS) grafts. From July 2002 to July 2009, 233 patients received a right liver graft with a middle hepatic vein from a living donor in our center. Recipients were stratified according to the graft weight to recipient standard liver volume (GW/SLV) ratio into 4 groups: >50% (n = 89), >40% to 50% (n = 85), >35% to 40% (n = 38), and ≤ 35% (n = 21). They were compared in terms of graft survivals, biliary stricture rates, renal function in terms of estimated glomerular filtration rate (eGFR), platelet counts, and graft function in terms of serum bilirubin and international normalized ratio (INR). The 5-year graft survivals for patients with GW/SLV of >50%, >40% to 50%, >35% to 40% and ≤ 35% were 88.8%, 88.2%, 81.5%, and 81.0%, respectively. Transplantation for hepatocellular carcinoma affected graft survivals (P = 0.02), but graft size did not (P = 0.66). There were no differences in frequency of biliary stricture (21.3% versus 17.1% versus 21.1% versus 28.6%; P = 0.75). At each year after transplant, their platelet counts (P = 0.12-0.65), eGFR (P = 0.49-0.91), bilirubin (P = 0.14-0.51), and INR (P = 0.20-0.98) remained comparable. SFS grafts with GW/SLV ≤ 35% and >35% to 40% had comparable long-term outcomes with larger liver grafts. Graft size did not affect long-term graft survivals. © 2015 American Association for the Study of Liver Diseases.

Phosphorus amendment reduces hepatic and renal oxidative stress in mallards ingesting lead-contaminated sediments

USGS Publications Warehouse

Hoffman, D.J.; Heinz, G.H.; Audet, D.J.

2006-01-01

Lead poisoning of waterfowl has been reported for decades in the Coeur d'Alene River Basin (CDARB) in Idaho as a result of the ingestion of lead-contaminated sediments. This study was conducted to determine whether the addition of phosphoric acid to CDARB sediments would reduce the bioavailability and toxicity of lead to the liver and kidney of mallards (Anas platyrhynchos). Mallards received diets containing 12% clean sediment (controls) or 12% sediment from three different CDARB sites containing 4520, 5390, or 6990 ug/g lead (dry weight) with or without phosphoric acid amendment. Liver and kidney lead concentrations were significantly higher in all CDARB treatment groups and ranged from geometric mean values of 18.2 (liver) and 28.7 (kidney) for the first 2 sites to 22.5 (liver) and 45.6 (kidney) ug/g (wet weight) for the third site. With amendments all liver lead concentrations were reduced 36 to 55%, and all kidney lead concentrations were lowered 54 to 73%. Unamended CDARB sediment from the third site resulted in the following hepatic effects: over 1.6-fold elevation of liver glutathione (reduced form; GSH) concentration, higher GSH S-transferase and oxidized glutathione (GSSG) reductase activities, and lower protein-bound thiols (PBSH) concentration. Renal effects included higher kidney GSH concentrations for all CDARB sites, with over 2.1-fold higher for the third site. Resulting kidney GSSG to GSH ratios were lower at two sites. At the third site, gamma-glutamyl transferase (GGT) activity was elevated, and lipid peroxidation as thiobarbituric acid-reactive substances (TBARS) was 1.7-fold greater. Amendment restored all hepatic variables as well as the renal variables TBARS and GGT so they did not differ from controls. Although amendments of phosphorus substantially reduced the bioavailability of lead and some of the adverse effects, lead concentrations in the tissues of mallards fed the amended sediments were still above those considered to be harmful to waterfowl under the present conditions.

Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure.

PubMed

Yaqoob, Noreen; Evans, Andrew; Foster, John R; Lock, Edward A

2014-09-02

Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has been shown to cause liver tumours in rodents and a small incidence of renal tubule tumours in male rats. The basis for the renal tubule injury is believed to be related to metabolism of TCE via glutathione conjugation to yield the cysteine conjugate that can be activated by the enzyme cysteine conjugate β-lyase in the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH) have been shown to cause formic aciduria which can cause renal injury after chronic exposure in rats. In this study we have compared the renal toxicity of TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or formic aciduria can account for the toxicity. Male rats were given TCE (500mg/kg/day) or TCE-OH at (100mg/kg/day) for 12 weeks and the extent of renal injury measured at several time points using biomarkers of nephrotoxicity and prior to termination assessing renal tubule cell proliferation. The extent of formic aciduria was also determined at several time points, while renal pathology and plasma urea and creatinine were determined at the end of the study. TCE produced a very mild increase in biomarkers of renal injury, total protein, and glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase in these biomarkers in urine. However, both chemicals produced a marked and sustained increase in the excretion of formic acid in urine to a very similar extent. The activity of methionine synthase in the liver of TCE and TCE-OH treated rats was inhibited by about 50% indicative of a block in folate synthesis. Both renal pathology and renal tubule cell proliferation were reduced after TCE and TCE-OH treatment compared to controls. Our findings do not clearly identify the pathway which is responsible for the renal toxicity of TCE but do provide some support for metabolism via glutathione conjugation. Copyright © 2014. Published by Elsevier Ireland Ltd.

Effect of Contrast Media on Single Shot EPI: Implications for Abdominal Diffusion Imaging

PubMed Central

Gulani, Vikas; Willatt, Jonathan M.; Blaimer, Martin; Hussain, Hero K.; Duerk, Jeffrey L.; Griswold, Mark A.

2010-01-01

Purpose The goal of this study was to determine the effect of contrast media on the signal behavior of single shot echo planar imaging (ssEPI) used for abdominal diffusion imaging. Materials and Methods The signal of a ssEPI spin echo sequence in a water phantom with varying concentrations of gadolinium was modeled with Bloch equations and the predicted behavior validated on a phantom at 1.5 T. Six volunteers were given gadolinium contrast, and signal intensity (SI) time courses for regions of interest (ROIs) in the liver, pancreas, spleen, renal cortex and medulla were analyzed. The Student's t-test was used to compare pre-contrast SI to 0, 1, 4, 5, 10, and 13 minutes following contrast. Results The results show that following contrast, ssEPI SI goes through a nadir, recovering differently for each organ. Maximal contrast related signal losses relative to pre-contrast signal are 20%, 20%, 53%, and 67%, for the liver, pancreas, renal cortex and medulla respectively. The SIs remain statistically below the pre-contrast values for 5, 4, and 1 minutes for the pancreas, liver, and spleen, and for all times measured for the renal cortex and medulla. Conclusion Abdominal diffusion imaging should be performed prior to contrast due to adverse effects on the signal in ssEPI. PMID:19856456

Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids

PubMed Central

Wang, Lirui; Hartmann, Phillipp; Haimerl, Michael; Bathena, Sai P.; Sjöwall, Christopher; Almer, Sven; Alnouti, Yazen; Hofmann, Alan F.; Schnabl, Bernd

2014-01-01

Background & aims Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. Methods We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2−/− mice. Results Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2−/− mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2−/− mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion. Conclusions Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte. PMID:24560660

Multiorgan failure following mass wasp stings.

PubMed

Lin, Cheng-Jui; Wu, Chih-Jen; Chen, Han-Hsiang; Lin, Hsin-Chang

2011-05-01

Wasp bites usually bring temporary discomfort and pain, but on occasion, they can cause serious infections and fatal allergic reactions. We report on a patient who experienced massive wasp stings and developed multiple organ failure, including acute kidney, hepatic failure, and circulatory collapse 4 days later. He was treated with aggressive fluid resuscitation, inotropic agent, intravenous injection of steroids, broad-spectrum antibiotics, and hemodialysis. After intensive treatment, his liver function recovered one month later. Recovery of renal function was delayed, and the patient needed temporary regular hemodialysis. The pathology of kidney biopsy showed acute tubulointerstitial nephritis. This case shows that toxic reactions following massive wasp attacks may happen several days after the fact and result in severe, multiorgan system dysfunction.

Diphenyl ditelluride intoxication triggers histological changes in liver, kidney, and lung of mice.

PubMed

da Luz, Sônia Cristina Almeida; Daubermann, Melissa Falster; Thomé, Gustavo Roberto; Dos Santos, Matheus Mülling; Ramos, Angelica; Torres Salazar, Gerson; da Rocha, João Batista Teixeira; Barbosa, Nilda Vargas

2015-01-01

Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 μmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 μmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 μmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 μmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung.

Simultaneous Occurrence of Varicella Zoster Virus-Induced Pancreatitis and Hepatitis in a Renal Transplant Recipient: A Case Report and Review of Literature

PubMed Central

Chhabra, Puneet; Ranjan, Priyadarshi; Bhasin, Deepak K

2017-01-01

Introduction: Gastrointestinal complications are common after renal transplantation, including oral lesions, esophagitis, gastritis, diarrhea, and colon carcinoma. The differential diagnosis is difficult in this scenario because multiple factors such as drugs, infections, and preexisting gastrointestinal disease come into play. Case Presentation: We report a case of varicella zoster virus-induced pancreatitis and hepatitis in a renal transplant recipient. The patient underwent renal transplantation 3 years earlier and now presented with severe pain in the epigastrium radiating to his back and had raised serum lipase levels and skin lesions characteristic of varicella. Liver enzyme levels were also elevated. He was started on a regimen of acyclovir. His pain improved in 24 hours, and liver enzyme levels returned to normal in 48 hours. Discussion: There is a paucity of literature on the simultaneous occurrence of varicella zoster virus-induced hepatitis and pancreatitis in both immunocompetent and immunocompromised patients. Our case highlights the gastrointestinal complications of varicella infection in immunocompromised patients that may precede the characteristic dermatologic manifestations, and the fact that rarely both hepatitis and pancreatitis may be seen. PMID:28333601

Acute-On-Chronic Liver Failure: Causes, Clinical Characteristics and Predictors of Mortality.

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan

2017-01-01

To determine the causes, characteristics and predictors of mortality in patients with acute-on-chronic liver failure (ACLF). Cross-sectional study. Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from July 2014 to June 2016. All patients with acute-on-chronic liver disease (ACLD) with ages > 12 were included. Patients with ACLF, as defined by the Asian Pacific Association for the Study of Liver (APASL, 2014) were identified. Predictors of mortality were identified using chi-square or Fisher's exact test. Included in the study were 72 patients with mean age of 36.71 years, 46 (63.9%) being males. Among them, 61 developed ACLF. Commonest causes of chronic liver disease (CLD) were chronic viral hepatitis (37, 51.4%) and autoimmune hepatitis (14, 19.4%). Commonest causes of acute liver injury (ALI) were acute viral hepatitis (24, 33.3%) and drug induced liver injury (DILI) (17, 23.6%). Among those with ACLF, 24 (39.3%) patients died with median survival of 17.1 ±13.5 days. Mortality was significantly associated with Child Turcotte Pugh (CTP) score ≥13 (p=0.010), model for end-stage liver disease (MELD) score ≥30 (p=0.001), age >40 years (p=0.036), organ failures (OF) ≥3 (p <0.0001), portosystemic encephalopathy (PSE) (p <0.0001), renal failure (p <0.0001) and urosepsis (p <0.0001). Acute viral hepatitis and DILI are commonest causes of ACLF. Mortality is high in ACLF patients having OF ≥3, CTP ≥13, MELD ≥30, age >40 years, PSE, renal failure and urosepsis.

Plasma protein biomarkers enhance the clinical prediction of kidney injury recovery in patients undergoing liver transplantation.

PubMed

Levitsky, Josh; Baker, Talia B; Jie, Chunfa; Ahya, Shubhada; Levin, Murray; Friedewald, John; Al-Saden, Patrice; Salomon, Daniel R; Abecassis, Michael M

2014-12-01

Biomarkers predictive of recovery from acute kidney injury (AKI) after liver transplantation (LT) could enhance decision algorithms regarding the need for liver-kidney transplantation or renal sparing regimens. Multianalyte plasma/urine kidney injury protein panels were performed immediately before and 1 month post-LT in an initial test group divided by reversible pre-LT AKI (rAKI = post-LT renal recovery) versus no AKI (nAKI). This was followed by a larger validation set that included an additional group: irreversible pre-LT AKI (iAKI = no post-LT renal recovery). In the test group (n = 16), six pre-LT plasma (not urine) kidney injury proteins (osteopontin [OPN], neutrophil gelatinase-associated lipocalin, cystatin C, trefoil factor 3, tissue inhibitor of metalloproteinase [TIMP]-1, and β-2-microglobulin) were higher in rAKI versus nAKI (P < 0.05) and returned to normal values with renal recovery post-LT. In the validation set (n = 46), a number of proteins were significantly higher in both rAKI and iAKI versus nAKI. However, only pre-LT plasma OPN (P = 0.009) and TIMP-1 (P = 0.019) levels were significantly higher in rAKI versus iAKI. Logistic regression modeling was used to correlate the probability of post-LT rAKI, factoring in both pre-LT protein markers and clinical variables. A combined model including elevated OPN and TIMP-1 levels, age <57, and absence of diabetes had the highest area under the curve of 0.82, compared to protein-only and clinical variable-only models. These data suggest that plasma protein profiles might improve the prediction of pre-LT kidney injury recovery after LT. However, multicenter, prospective studies are needed to validate these findings and ultimately test the value of such protein panels in perioperative management and decision making. © 2014 by the American Association for the Study of Liver Diseases.

Functions of the Renal Nerves.

ERIC Educational Resources Information Center

Koepke, John P.; DiBona, Gerald F.

1985-01-01

Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis.

PubMed

Tajiri, Kazuto; Tokimitsu, Yoshiharu; Ito, Hiroyuki; Atarashi, Yoshinari; Kawai, Kengo; Minemura, Masami; Yasumura, Satoshi; Takahara, Terumi; Shimizu, Yukihiro; Sugiyama, Toshiro

2018-05-31

The study aimed to evaluate the effects of tolvaptan treatment on survival of patients with decompensated liver cirrhosis with refractory ascites. This multicenter, retrospective, observational study included patients with cirrhosis who were treated with tolvaptan for hepatic ascites refractory to conventional diuretics. Patients who could and could not decrease accompanying diuretics within 1 month after tolvaptan administration were defined as the "Decreased" and "Not-decreased" groups, respectively. Median body weight change 1 week after tolvaptan treatment was -1.95 kg, with the 50% of patients experiencing a 2 kg/week reduction. Spot urinary sodium was found to be a better predictor of tolvaptan response than liver function and liver fibrosis markers. Median survival was significantly longer (not reached versus 116 days, p = 0.005) and serum creatinine concentrations 12 weeks after tolvaptan administration significantly lower (0.99 vs. 1.55 mg/dL, p < 0.05) in the Decreased than in the Not-decreased group. Multivariate analysis showed that the presence of viable hepatocellular carcinoma (hazards ratio [HR] 2.14, p = 0.02) and a decrease in diuretics were independently prognostic of survival (HR 0.36, p < 0.01). The maintenance of renal function is essential in enhancing survival of patients with cirrhosis. Doses of diuretics should be adjusted appropriately during tolvaptan treatment. © 2018 S. Karger AG, Basel.

Supplementation of Ascorbic Acid in Weanling Horses Following Prolonged Transportation

PubMed Central

Ralston, Sarah; Stives, Michelle

2012-01-01

Simple Summary Horses normally synthesize adequate amounts of ascorbic acid (vitamin C) in their liver to meet their needs for the vitamin. However, prolonged stress results in low plasma concentrations and reduced immune function. Weanling horses were supplemented with ascorbic acid for 5 or 10 days or no ascorbic acid (4 per group) following 50+ hours of transportation. Supplementation caused increases in plasma concentrations but both supplemented groups had decreased plasma ascorbic acid for 1 to 3 weeks following cessation of supplementation, possibly due to suppressed synthesis. Supplementation of ascorbic acid following prolonged stress will increase plasma concentrations, but prolonged supplementation should be avoided. Abstract Though horses synthesize ascorbic acid in their liver in amounts that meet their needs under normal circumstances, prolonged stress results in low plasma concentrations due to enhanced utilization and renal excretion and can reduce immune function. It was hypothesized that plasma ascorbic acid could be maintained in weanling horses by oral supplementation following prolonged transportation. Weanlings were supplemented with no ascorbic acid (Tx 0: n = 4), 5 grams ascorbic acid twice daily for 5 days (Tx 1: n = 4) or for 10 days (Tx 2: n = 4) following >50 hours of transportation. Supplementation caused slight (P < 0.2) increases in plasma ascorbic acid concentrations. Both supplemented groups had decreased (P < 0.05) plasma concentrations for 1 to 3 weeks following cessation of supplementation, possibly due to increased renal excretion or suppressed hepatic synthesis. Supplementation of ascorbic acid following prolonged stress will increase plasma concentrations, but prolonged supplementation should be avoided. PMID:26486916

Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).

PubMed

Sakaida, Isao; Terai, Shuji; Kurosaki, Masayuki; Yasuda, Moriyoshi; Okada, Mitsuru; Bando, Kosuke; Fukuta, Yasuhiko

2017-10-01

Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings. Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6 months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure. Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38 kg on day 7 and -3.52 kg on day 14. Ascites and bloated feeling was significantly improved within 14 days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146 mEq/L was observed in 12 patients (2.7%). In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained. © 2016 The Japan Society of Hepatology.

Vasopressin and a nonpeptide antidiuretic hormone receptor antagonist (OPC-31260).

PubMed

Burrell, L M; Phillips, P A; Stephenson, J M; Risvanis, J; Johnston, C I

1994-03-01

The development of nonpeptide orally active AVP analogues has provided a new tool with which to assess the physiological and pathophysiological role of vasopressin (AVP). We have previously characterised the nonpeptide vasopressin V1 receptor antagonist OPC-21268, and now report the in vitro characterisation of the nonpeptide V2 receptor antagonist OPC-31260 in the rat. OPC-31260 caused a concentration-dependent displacement of the selective AVP V2 receptor antagonist radioligand, [3H]desGly-NH2(9)[d(CH2)5, D-Ile2,Ile4]AVP from V2 receptors in rat kidney medulla membranes. The concentration of OPC-31260 that displaced 50% of specific AVP binding (IC50) was 20 +/- 2 nmol/l for renal V2 receptors. OPC-31260 also caused a concentration-dependent displacement of the selective AVP V1 receptor antagonist radioligand, [125I]-[d(CH2)5,sarcosine7]AVP from V1 receptors in both rat liver and kidney medulla membranes. The IC50 was 500 +/- 30 nmol/l for both renal and liver V1 receptors. After oral administration to rats, OPC-31260 was an effective inhibitor of AVP at renal V2 and liver V1 receptors in a time-dependent manner. In vitro binding kinetic studies showed that OPC-31260 was a competitive antagonist at both the renal V2 receptor and the hepatic V1 receptor. OPC-31260 is a nonpeptide, orally effective competitive inhibitor of AVP with a V2:V1 receptor selectivity ratio of 25:1 indicating relative V2 receptor selectivity.

Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy.

PubMed

Sandoval-Sus, Jose D; Mogollon-Duffo, Francis; Patel, Ankita; Visweshwar, Nathan; Laber, Damian A; Kim, Richard; Jagal, Michael V

2017-01-01

We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient's wishes before admission, and after agreement with the family, nivolumab (3 mg/kg every 2 weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5 months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response. We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options. Unlike classic cytotoxic chemotherapy, which relies on preserved organ function to ameliorate potential severe side effects (i.e. myelosuppression), elimination of monoclonal antibodies is fairly independent of baseline renal and hepatic function since they are usually metabolized by circulating phagocytes and/or by their target antigen-expressing cell.

Kidney and liver transplants from donors after cardiac death: initial experience at the London Health Sciences Centre.

PubMed

Hernandez-Alejandro, Roberto; Caumartin, Yves; Chent, Cameron; Levstik, Mark A; Quan, Douglas; Muirhead, Norman; House, Andrew A; McAlister, Vivian; Jevnikar, Anthony M; Luke, Patrick P W; Wall, William

2010-04-01

The disparity between the number of patients waiting for an organ transplant and availability of donor organs increases each year in Canada. Donation after cardiac death (DCD), following withdrawal of life support in patients with hopeless prognoses, is a means of addressing the shortage with the potential to increase the number of transplantable organs. We conducted a retrospective, single-centre chart review of organs donated after cardiac death to the Multi-Organ Transplant Program at the London Health Sciences Centre between July 2006 and December 2007. In total, 34 solid organs (24 kidneys and 10 livers) were procured from 12 DCD donors. The mean age of the donors was 38 (range 18-59) years. The causes of death were craniocerebral trauma (n = 7), cerebrovascular accident (n = 4) and cerebral hypoxia (n = 1). All 10 livers were transplanted at our centre, as were 14 of the 24 kidneys; 10 kidneys were transplanted at other centres. The mean renal cold ischemia time was 6 (range 3-9.5) hours. Twelve of the 14 kidney recipients (86%) experienced delayed graft function, but all kidneys regained function. After 1-year follow-up, kidney function was good, with a mean serum creatinine level of 145 (range 107-220) micromol/L and a mean estimated creatinine clearance of 64 (range 41-96) mL/min. The mean liver cold ischemia time was 5.8 (range 5.5-8) hours. There was 1 case of primary nonfunction requiring retransplantation. The remaining 9 livers functioned well. One patient developed a biliary anastomotic stricture that resolved after endoscopic stenting. All liver recipients were alive after a mean follow-up of 11 (range 3-20) months. Since the inception of this DCD program, the number of donors referred to our centre has increased by 14%. Our initial results compare favourably with those from the transplantation of organs procured from donors after brain death. Donation after cardiac death can be an important means of increasing the number of organs available for transplant, and its widespread implementation in Canada should be encouraged.

Endovascular management of arterial injuries after blunt or iatrogenic renal trauma

PubMed Central

Chevallier, Olivier; Gehin, Sophie; Midulla, Marco; Berthod, Pierre-Emmanuel; Galland, Christophe; Briche, Pascale; Duperron, Céline; Majbri, Nabil; Mousson, Christiane; Falvo, Nicolas

2017-01-01

The kidney is the third most common abdominal organ to be injured in trauma, following the spleen and liver, respectively. The most commonly used classification scheme is the American Association for the Surgery of Trauma (AAST) classification of blunt renal injuries, which grades renal injury according to the size of laceration and its proximity to the renal hilum. Arteriovenous fistula and pseudoaneurysm are the most common iatrogenic biopsy-related or surgery-related vascular injuries in native kidneys. The approach to renal artery injuries has changed over time from more aggressive intervention to more conservative observational or endovascular management, including selective transcatheter arterial embolization (TAE) and the placement of stents/stent grafts. In this article, we describe the role and technical aspects of endovascular interventions in the management of arterial injuries after blunt or iatrogenic renal trauma. PMID:28932700

Differential effects of liver steatosis on pharmacokinetic profile of two closely related hepatoselective NO-donors; V-PYRRO/NO and V-PROLI/NO.

PubMed

Kus, Kamil; Kus, Edyta; Zakrzewska, Agnieszka; Jawien, Wojciech; Sitek, Barbara; Walczak, Maria; Chlopicki, Stefan

2017-06-01

To analyze the effect of liver steatosis and obesity on pharmacokinetic profile of two structurally-related liver-selective NO-donors - V-PYRRO/NO and V-PROLI/NO. C57BL/6 mice were fed control or high-fat diet for 15 weeks to induced liver steatosis and obesity (HFD mice). Pharmacokinetics and renal elimination studies were conducted in vivo following iv dosing of V-PYRRO/NO and V-PROLI/NO (0.03mmol/kg). Hepatic clearance was evaluated ex vivo in the isolated perfused mice liver and in vitro with the use of liver microsomes. V-PYRRO/NO and V-PROLI/NO, despite similar structure, displayed different pharmacokinetic properties. V-PYRRO/NO was uptaken and metabolized by the liver, while V-PROLI/NO was eliminated unchanged with urine. In HFD mice, despite increased CYP450 metabolism of V-PYRRO/NO the elimination rate was slower most likely due to the impairment of hepatic microcirculation caused by liver fat accumulation. In turn, in HFD mice renal clearence of V-PROLI/NO was accelerated and volume of distribution was increased most likely due to additional intracellular water in HFD mice. The pharmacokinetics of V-PROLI/NO, the novel proline-based analog of V-PYRRO/NO with additional single carboxylic acid moiety, attached to the molecule of V-PYRRO/NO to improve the water solubility, was differently affected by liver steatosis and obesity as compared with the parent compound V-PYRRO/NO. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Clinical spectrum of primary hyperoxaluria type 1: Experience of a tertiary center.

PubMed

Soliman, Neveen A; Nabhan, Marwa M; Abdelrahman, Safaa M; Abdelaziz, Hanan; Helmy, Rasha; Ghanim, Khaled; Bazaraa, Hafez M; Badr, Ahmed M; Tolba, Omar A; Kotb, Magd A; Eweeda, Khaled M; Fayez, Alaa

2017-05-01

Primary hyperoxalurias are rare inborn errors of metabolism resulting in increased endogenous production of oxalate that leads to excessive urinary oxalate excretion. Diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. We characterized the clinical presentation as well as renal and extrarenal phenotypes in PH1 patients. This descriptive cohort study included patients with presumable PH1 presenting with nephrolithiasis and/or nephrocalcinosis (NC). Precise clinical characterization of renal phenotype as well as systemic involvement is reported. AGXT mutational analysis was performed to confirm the diagnosis of PH1. The study cohort included 26 patients with presumable PH1 with male to female ratio of 1.4:1. The median age at time of diagnosis was 6 years, nevertheless the median age at initial symptoms was 3 years. Thirteen patients (50%) were diagnosed before the age of 5 years. Two patients had no symptoms and were diagnosed while screening siblings of index patients. Seventeen patients (65.4%) had reached end-stage renal disease (ESRD): 6/17 (35.3%) during infancy, 4/17 (23.5%) in early childhood and 7/17 (41.29%) in late childhood. Two patients (7.7%) had clinically manifest extra renal (retina, heart, bone, soft tissue) involvement. Mutational analysis of AGXT gene confirmed the diagnosis of PH1 in 15 out of 19 patients (79%) where analysis had been performed. Fifty percent of patients with maintained renal functions had projected 10 years renal survival. PH1 is a heterogeneous disease with wide spectrum of clinical, imaging and functional presentation. More than two-thirds of patients presented prior to the age of 5 years; half of them with the stormy course of infantile PH1. ESRD was the commonest presenting manifestation in two-thirds of our cohort. Copyright © 2016 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Extracolonic Findings on Computed Tomography (CT) Colonography

ClinicalTrials.gov

2017-03-16

Solitary Pulmonary Nodules; Multiple Pulmonary Nodules; Renal Neoplasms; Adrenal Gland Neoplasms; Aortic Aneurysm, Abdominal; Liver Neoplasms; Adnexal and Skin Appendage Neoplasms; Lymphadenopathy; Pancreatic Neoplasms

Protective Effects of the Third Generation Vasodilatory Βeta - Blocker Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats

PubMed Central

Atwa, Ahmed; Hegazy, Rehab; Mohsen, Rania; Yassin, Neamat; Kenawy, Sanaa

2017-01-01

BACKGROUND: Renal dysfunction is very common in patients with advanced liver cirrhosis and portal hypertension. The development of renal failure in the absence of clinical, anatomical or pathological causes renal of failure is termed hepatorenal syndrome (HRS). AIM: The present study was constructed to investigate the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)-induced HRS in rats. MATERIAL AND METHODS: Rats were treated with Nebi for ten successive days. On the 8th day of the experiment, they received a single dose of Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration. Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), total nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase-1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also assessed. Finally, histopathological examination was performed. RESULTS: Nebi attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal-induced oxidative stress and inflammatory recruitment. CONCLUSION: Results demonstrated both nephroprotective and hepatoprotective effects of Nebi against HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic and NO-releasing properties. PMID:29362613

Serum sodium identifies patients with cirrhosis at high risk of hepatorenal syndrome.

PubMed

Janičko, M; Veselíny, E; Abraldes, J G; Jarčuška, P

2013-07-01

Although the precipitating events of hepatorenal syndrome (HRS) development have been well characterized, the actual baseline risk of these events resulting in HRS is much less studied. To assess the predictive value of hyponatremia in the development of HRS. We performed a retrospective observational cohort study including consecutive patients with decompensated liver cirrhosis and normal creatininemia admitted to tertiary center in Slovakia. Patients were censored at two months, development of renal failure, classified either as HRS or renal failure not fulfilling criteria of HRS, was the main outcome. Out of 202 patients 18 developed HRS and 14 renal failure not fulfilling the HRS criteria. A significant difference was found between patients with and without HRS in serum sodium (135.76 ± 5.01 vs. 130.78 ± 3.574 mmol/l; p < 0.0001), creatinine, (81 ± 20.11 vs. 98.18 ± 25.032 µmol/l; p = 0.006), bilirubin (90.4 ± 104.82 vs.175.42 ± 174.12 µmol/l; p < 0.0001), MELD (15.17 ± 5.52 vs. 21.61 ± 6.0; p < 0.0001) and MELD-Na score (19.96 ± 6.0 vs. 25.89 ± 4.96; p < 0.0001). Sodium, creatinine, bilirubin, MELD, MELD-Na score were found to be significant predictors of HRS in univariate analysis. Multivariate analysis two prediction models (Model 1: Bilirubin, creatinin, sodium and Model 2: Sodium, MELD) showed that sodium together with creatinine are the strongest HRS predictors, followed by bilirubin or MELD score. Serum levels of sodium, creatinine and parameters of liver function are important predictors of hepatorenal syndrome. © Georg Thieme Verlag KG Stuttgart · New York.

Hepatic Regeneration and Reno-Protection by Fish oil, Nigella sativa Oil and Combined Fish Oil/Nigella sativa Volatiles in CCl4 Treated Rats.

PubMed

Al-Okbi, Sahar Y; Mohamed, Doha A; Hamed, Thanaa E; Edris, Amr E; Fouda, Karem

2018-03-01

The aim of the present research was to investigate the effect of fish oil, crude Nigella sative oil and combined fish oil/Nigella sative volatile oil as hepato-regenerative and renal protective supplements. The oils were administered as emulsions to rat model with liver injury induced by CCl 4 . Plasma activities of transaminases (AST and ALT) were evaluated as liver function indicators, while plasma creatinine and urea and creatinine clearance were determined as markers of kidney function. Plasma malondialdehyde (MDA), nitrite (NO) and tumor necrosis factor-α (TNF-α) were estimated to assess the exposure to oxidative stress and subsequent inflammation. Liver fat was extracted and their fatty acids´ methyl esters were determined using gas chromatography. Results showed that plasma activities of AST and ALT were significantly higher in CCl 4 control group compared to control healthy group. Plasma levels of creatinine and urea increased significantly in CCl 4 control, while creatinine clearance was reduced significantly in the same group. All rat treated groups given the three oil emulsions showed improvement in liver function pointing to the initiation of liver regeneration. The combination of fish oil/Nigella sative volatiles showed the most promising regenerative activity. Oxidative stress and inflammation which were increased significantly in CCl 4 control group showed improvement on administration of the three different oil emulsions. Fatty acids methyl ester of liver fat revealed that rats treated with fish oil/Nigella sative volatile oil presented the highest content of unsaturated fatty acids (45.52% ± 0.81) while fish oil showed the highest saturated fatty acids (53.28% ± 1.68). Conclusion; Oral administration of oil emulsions of native fish oil, Nigella sative crude oil and combined fish oil/Nigella sative volatile oil reduced liver and kidney injury in rat model of CCl 4 through exerting anti-inflammatory and antioxidant activity. Fish oil/Nigella sative volatile oil emulsion was the most promising hepato-regenerative and reno-protective formula among the different groups.

Renal water handling in rats with decompensated liver cirrhosis.

PubMed

Jonassen, T E; Christensen, S; Kwon, T H; Langhoff, S; Salling, N; Nielsen, S

2000-12-01

The present study was performed to investigate the renal handling of water in rats with decompensated liver cirrhosis. Liver cirrhosis was induced by intraperitoneal administration of carbon tetrachloride twice weekly for 16 wk. Control rats were treated with vehicle. The cirrhotic rats developed severe disturbances in water homeostasis: urine production was decreased and hyperosmotic, the rats had significantly decreased plasma sodium concentration and ascites, and the ability to excrete an intravenous water load was significantly impaired. Plasma concentrations of vasopressin and aldosterone were increased. Mean arterial pressure, glomerular filtration rate (GFR), and fractional lithium excretion were decreased. Acute vasopressin type 2-receptor blockade with the selective nonpeptide antagonist OPC-31260 (800 microg. kg(-1). h(-1)) was performed during conditions whereby volume depletion was prevented by computer-driven, servo-controlled intravenous volume replacement with 150 mM glucose. The aquaretic response to OPC-31260 was similar in cirrhotic and control rats. However, the OPC 31260-induced rises in fractional water excretion (delta V/GFR; +24%) and fractional distal water excretion (delta V/C(Li); +46%) were significantly increased in the cirrhotic rats, where V is flow rate and delta is change. This suggests that vasopressin-mediated renal water reabsorption capacity was increased in the cirrhotic rats. Semiquantitative immunoblotting revealed that the expression of the vasopressin-regulated water channel aquaporin-2 was unchanged in membrane fractions of both whole kidney and inner medulla from cirrhotic rats. Together, these results suggest a relative escape from vasopressin on collecting duct water reabsorption in rats with decompensated liver cirrhosis.

Hyperemesis gravidarum presenting as jaundice and transient hyperthyroidism complicated with acute pancreatitis.

PubMed

Weng, Meng Tzu; Wei, Shu Chen; Wong, Jau Min; Chang, Tien Chun

2005-03-01

Hyperemesis gravidarum is an extreme form of nausea and vomiting during pregnancy. Its presenting symptoms include vomiting, disturbed nutrition, electrolyte imbalance, ketosis, extreme weight loss, renal and/or liver damage. It is rare for a hyperemesis gravidarum patient to present with jaundice, hyperthyroidism and idiopathic acute pancreatitis during the same hospitalization period. Here, we report such a case. A 25-year-old pregnant woman without underlying liver or thyroid disease was admitted due to jaundice noted for 2 days at 8 weeks of gestational age. Hyperthyroidism symptoms of tachycardia and finger tremor also bothered her. After treatment with parenteral fluid and antithyroid agents, her clinical condition improved. However, an episode of idiopathic pancreatitis occurred after nausea and vomiting subsided. Bowel rest with parenteral fluid and nutrition supplement was given and the increased pancreatic enzyme level gradually subsided. Follow-up liver and thyroid function were normal after gestational age of 26 weeks. She delivered a healthy female baby without low birth body weight at gestational age of 39 weeks. Rapid diagnosis and supportive care are important for the hyperemesis gravidarum patient with the complication of acute pancreatitis.

Rejection is less common in children undergoing liver transplantation for hepatoblastoma.

PubMed

Ruth, N D; Kelly, D; Sharif, K; Morland, B; Lloyd, C; McKiernan, P J

2014-02-01

To compare the incidence of acute histologically proven rejection in children who have had a liver transplant for hepatoblastoma with a control group of children transplanted for biliary atresia (EHBA). A retrospective case notes based study was performed. Twenty patients were identified with hepatoblastoma who were transplanted at a single unit between 1991 and 2008. These were matched as closely as possible for age, gender, year of transplant and type of immunosuppression used to the control group transplanted for biliary atresia (n = 60). There was a significant decrease in rate of acute rejection as assessed by the rejection activity index (RAI) in the hepatoblastoma group (75% vs. 50%, respectively, p < 0.04). Chronic rejection was rare in both groups, but twice as common in the biliary atresia group. Equal levels of immunosuppression were achieved in both groups. Renal function was noted to be reduced one yr post-transplant in both groups, as previously reported. A modified immunosuppression regimen could be considered in children with hepatoblastoma undergoing liver transplantation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Preliminary study of a traditional Chinese medicine formula in systemic lupus erythematosus patients to taper steroid dose and prevent disease flare-up.

PubMed

Liao, Yen-Nung; Liu, Ching-Shen; Tsai, Tong-Rong; Hung, Yu-Chiang; Chang, Shun-Jen; Lin, Hong-Long; Chen, Ying-Chou; Lai, Han-Ming; Yu, Shan-Fu; Chen, Chung-Jen

2011-07-01

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Prolonged complete remission is rare. Most patients with SLE need long-term treatment with glucocorticoid and immunomodulators. However, side effects because of the above medications are common. We evaluated the effect of adding-on Dan-Chi-Liu-Wei combination (DCLWC) on SLE patients with conventional therapy in tapering steroid and preventing disease flare-up. This was a double-blind and randomized controlled trial. Sixty-six SLE patients were recruited into this study and 53 patients who fulfilled the 1997 revised criteria for the classification of SLE with an SLE disease activity index (SLEDAI) score of 2-12 and a steroid (measured with prednisolone) daily dose of less than 20mg/d were enrolled. The patients were randomized into either an experimental or control group. We checked the urine analysis, hemogram, liver function, renal function, C3, C4, erythrocyte sedimentation rate, and anti-dsDNA, evaluated the SLEDAI score, and recorded the steroid dose at 0 months, 3 months, and 6 months, respectively. After 6 months of study, the C4 and blood urea nitrogen level revealed a statistically significant difference in either group. There was a tendency toward a decreased SLEDAI score in the experimental group (p=0.083) but not in the control group (p=0.867). The steroid dose was not statistically significant in either group. Renal function and liver function revealed no statistically significant statistics changes in either group. Adding-on DCLWC to conventional therapy for the treatment of SLE was safe and might have a borderline effect in decreasing disease activity, but it was not possible to taper the dosage of steroid after 6 months of clinical trial. Therefore, a long-term follow-up and a large-scale study are necessary to confirm the effect of DCLWC. Copyright © 2011 Elsevier Taiwan LLC. All rights reserved.

Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrill, Joshua A.; Hukkanen, Renee R.; Lawson, Marie

2013-10-15

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague–Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expressionmore » of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 μg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ∼ 30–45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species. - Highlights: • An AHR knockout rat was generated on a Sprague–Dawley outbred background. • AHR-KO rats lack expression of AHR protein. • AHR-KO rats are insensitive to TCDD-mediated effects. • Data suggests difference in the role of AHR in tissue development of rats and mice. • Abnormalities in vascular development are observed in AHR-KO mouse, but not rat. • Renal pathology is observed in AHR-KO rat, but not mouse.« less

Bile duct epithelial tight junctions and barrier function

PubMed Central

Rao, R.K.; Samak, G.

2013-01-01

Bile ducts play a crucial role in the formation and secretion of bile as well as excretion of circulating xenobiotic substances. In addition to its secretory and excretory functions, bile duct epithelium plays an important role in the formation of a barrier to the diffusion of toxic substances from bile into the hepatic interstitial tissue. Disruption of barrier function and toxic injury to liver cells appear to be involved in the pathogenesis of a variety of liver diseases such as primary sclerosing cholangitis, primary biliary cirrhosis and cholangiocarcinoma. Although the investigations into understanding the structure and regulation of tight junctions in gut, renal and endothelial tissues have expanded rapidly, very little is known about the structure and regulation of tight junctions in the bile duct epithelium. In this article we summarize the current understanding of physiology and pathophysiology of bile duct epithelium, the structure and regulation of tight junctions in canaliculi and bile duct epithelia and different mechanisms involved in the regulation of disruption and protection of bile duct epithelial tight junctions. This article will make a case for the need of future investigations toward our understanding of molecular organization and regulation of canalicular and bile duct epithelial tight junctions. PMID:24665411

Evaluation of renal function in patients with a main renal stone larger than 1 cm and perioperative renal functional change in minimally invasive renal stone surgery: a prospective, observational study.

PubMed

Piao, Songzhe; Park, Juhyun; Son, Hwancheol; Jeong, Hyeon; Cho, Sung Yong

2016-05-01

To compare the perioperative relative renal function and determine predictors of deterioration and recovery of separate renal function in patients with renal stones >10 mm and who underwent mini-percutaneous nephrolithotomy or retrograde intra-renal surgery. A main stone >10 mm or stones growing, high-risk stone formers and extracorporeal shock-wave lithotripsy-resistant stones were prospectively included in 148 patients. Patients with bilateral renal stones and anatomical deformities were excluded. Renal function was evaluated by estimated glomerular filtration rate, 99m-technetium dimercaptosuccinic acid and 99m-technetium diethylenetriamine pentaacetate prior to intervention and at postoperative 3 months. Logistic regression analyses were performed to find predictors of functional deterioration and recovery. The overall stone-free rate was 85.1 %. A third of patients (53/148, 35.8 %) with renal stones >10 mm showed deterioration of separate renal function. Mean renal function of operative sites showed 58.2 % (36.8 %/63.2 %) of that of contralateral sites in these patients. Abnormal separate renal function showed postoperative recovery in 31 patients (58.5 %). Three cases (5.7 %) showed deterioration of separate renal function despite no presence of remnant stones. Improvement rates of the abnormal separate renal function did not differ according to the type of surgery. The presence of hydronephrosis and three or more stones were significant predictors for renal function deterioration. Female gender and three or more stones were significantly correlated with postoperative recovery. Mini-percutaneous nephrolithotomy or retrograde intra-renal surgery was effective and safe for renal function preservation. Patients with multiple large stones should be considered for candidates of active surgical removal.

Third-stage larvae of the enoplid nematode Dioctophyme renale (Goeze, 1782) in the freshwater turtle Trachemys dorbigni from southern Brazil.

PubMed

Mascarenhas, C S; Müller, G

2015-09-01

The giant kidney worm Dioctophyme renale is normally found in wild carnivores and domestic dogs, with aquatic oligochaetes acting as intermediate hosts. In the present study a prevalence of 50% of third-stage larvae of D. renale was recorded in 60 specimens of the freshwater turtle Trachemys dorbigni from southern Brazil. Larvae were encysted in muscles, the coelomic cavity and mesentery, the serous lining of the stomach and on the surfaces of the lung, heart, liver, pancreas, spleen and intestines. There are no previous records of reptiles being part of the life cycle of D. renale, although fish and amphibians normally act as paratenic hosts. This is the first report of third-stage D. renale larvae in the freshwater turtle, T. dorbigni.

Hepatic extraction and renal production of 3,3'-diiodothyronine and 3',5'-diiodothyronine in man.

PubMed Central

Faber, J; Faber, O K; Lund, B; Kirkegaard, C; Wahren, J

1980-01-01

The sequential deiodination of thyroxine (T4) gives rise to several iodothyronine analogs including 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2). In vitro animal studies suggest that the liver and the kidneys are the main sites of both formation and degradation of 3,3'-T2 and 3',5'-T2. To determine the metabolism of 3,3'-T2 and 3',5'-T2 in human liver and kidneys plasma samples were obtained from (a) a brachial artery and a hepatic vein in 20 normal subjects, and from (b) a femoral artery and a renal vein in 11 normal subjects. Further, the hepatic plasma flow (a) and the renal plasma flow (b) were determined. Both plasma 3,3'-T2 and 3',5'-T2 levels were reduced in the hepatic venous blood as compared to arterial values (1.09 +/- 0.40 vs. 1.75 +/- 0.74 ng/dl (P < 0.02)) (mean +/- 1 SD). This resulted in a hepatic extraction of both, 3,3'-T2 and 3',5'-T2, which averaged 8.2 and 5.2 microgram/d, respectively. Plasma 3,3'-T2 as well as 3'5'-T2 levels were higher in the renal vein as compared to arterial values, 1.49 +/- 0.42 vs. 1.39 +/- 0.45 ng/dl (P < 0.05) and 2.35 +/- 0.83 vs. 2.09 +/- 0.81 ng/dl (P < 0.05), respectively. This positive venoarterial difference implies a net production of 3,3'-T2 and 3',5'-T2 in the kidneys of 1.2 and 3.0 microgram/d, respectively. It is concluded that the liver is an important site of 3,3'-T2 and 3',5'-T2 extraction in normal man. In contrast, the renal production of 3,3'-T2 as well as 3'5'-T2 exceeds the degradation and urinary excretion. PMID:6776146

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Genetic analysis--a diagnostic tool for primary hyperoxaluria type I.

PubMed

Milosevic, Danko; Rinat, Choni; Batinic, Danica; Frishberg, Yaacov

2002-11-01

Primary hyperoxaluria type I is an autosomal recessive metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of disease, ranging from renal failure in infancy to mere renal stones in late adulthood. The diagnosis may be suspected when clinical signs and increased urinary oxalate and glycolate excretion present, and is confirmed by the measurement of decreased alanine:glyoxylate aminotransferase activity in a liver sample. The enzymatic assay is not readily available to pediatric nephrologists in many parts of the world. We describe three families from Croatia in whom the diagnosis of primary hyperoxaluria was solely based on clinical findings that included nephrolithiasis and nephrocalcinosis accompanied by increased urinary oxalates and glycolate excretion, as enzymatic assays of liver samples could not be performed. Mutation analysis of the AGXT gene encoding the defective enzyme confirmed the diagnosis, revealing three alleles carrying the C156ins mutation and two the G630A mutation. Screening first-degree relatives for the relevant mutation disclosed an asymptomatic affected sibling. Mutation analysis of the AGXT gene is a non-invasive and accurate tool for the diagnosis of type I primary hyperoxaluria that may replace enzymatic assays of liver biopsies.

Localized intestinal perforations as a potential complication of brain hypothermic therapy for perinatal asphyxia.

PubMed

Nishizaki, Naoto; Maiguma, Atsuko; Obinata, Kaoru; Okazaki, Tadaharu; Shimizu, Toshiaki

2016-01-01

Brain hypothermic therapy (BHT) is becoming a frequently used standard of care for perinatal asphyxia. Although cardiovascular side effects, coagulation disorders, renal impairment, electrolyte abnormalities, impaired liver function, opportunistic infections, and skin lesions are well-known adverse effects of BHT in newborns, little information is available on the clinical features of intestinal perforation-related BHT. We herein report a case of therapeutic brain cooling for perinatal asphyxia complicated by localized intestinal perforation. In practice, the neonatologist should be aware that intestinal perforation in an infant with perinatal asphyxia is possible, particularly following BHT.

[The specificity between "fei and dachang" in the lung injury of rats with ulcerative colitis].

PubMed

Zhu, Li; Wang, Xin-yue; Yang, Xue; Jing, Shan; Zhou, Bo; Huang, Xiu-xia; Jia, Xu

2013-03-01

To observe the features of bronchopulmonary lesions in ulcerative colitis (UC) rats and the specificity with Fei and Dachang, thus providing reliance for the theory of "intestinal diseases involved Fei". The UC rat model was duplicated by using rabbit intestine mucosa tissue allergenic model and TNBS-ethanol model. A normal rat group was set up as the control. The pulmonary functions [including inspiratory resistance (Ri), expiratory resistance (Re), forced vital capacity (FVC); FEV. 2/FVC, maximal voluntary ventilation (MVV), forced expiratory flow rate (FEF25% - 75%)], and indicators of liver and kidney functions [serum alanine aminotransferase (ALT), aspartate amino transferase (AST), blood urea nitrogen (BUN), and creatinine (Cr)] were detected in the two groups. The pathological changes of colon, lung, liver, and kidney were observed in the two groups. Rats in the model group in both acute and chronic stages had weight loss, mucus and loose stool. Partial rats had such symptoms as dyspnea, shortness of breath, and wheezing. Compared with the normal group, the MW, FVC, FEV0.2 and FEF25% -75% in the acute stage; Ri, Re, MVV, FVC, and FEF25% - 75% in the chronic stage all significantly decreased (P <0.05, P <0.01), and FEV0.2/FVC significantly increased in the model group (P <0.05). The pathological results showed interstitial pneumonia and pulmonary interstitial fibrosis in the model group. But the indicators of liver and kidney functions were all in the normal range. No obvious pathological change was seen in the renal and liver tissues in the two groups. UC could specifically induce bronchopulmonary lesions. Lung injury was one of UC's intestinal manifestations. The theory of "Fei and Dachang being interior-exteriorly correlated" was demonstrated from the theory of "intestinal diseases involved Fei".

Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats.

PubMed

Gargouri, M; Magné, C; Ben Amara, I; Ben Saad, H; El Feki, A

2017-02-28

Lead (Pb) is a highly toxic metal present in the environment. It causes disturbances of several functions, including hematologic, renal, reproductive and nervous ones. Preventive or curative use of medicinal plants against these disorders may be a promising and safe therapeutic strategy. This study evaluated the hepatic toxic effects of prenatal exposure to lead in rats and the possible protective effect of dandelion (Taraxacum officinale) added to the diet. Female rats were given a normal diet (control) or a diet enriched with dandelion (treated). In addition, lead acetate was administered to half of the rats through drinking water from the 5th day of gestation until the 14th day postpartum. Lead toxicity was evaluated in their offspring by measuring body and liver weights, plasma biochemical parameters, liver damage, as well as protein content and activities of antioxidant enzymes in the liver tissues. Lead poisoning of mothers caused lead deposition in blood and stomach of their pups as well as hepatic tissue damages. Moreover, significant decreases in liver weight and protein content were found. Lead treatment caused oxidative stress and marked changes in the activity of antioxidant enzymes. However, no damages or biochemical changes were observed in puppies from the rats co-treated with lead and dandelion. These results indicate that supplementation of pregnant and lactating rats with dandelion protects their offspring against lead poisoning, likely through reduction of oxidative stress and liver damages.

Microvillous inclusion disease: how to improve the prognosis of a severe congenital enterocyte disorder.

PubMed

Halac, Ugur; Lacaille, Florence; Joly, Francisca; Hugot, Jean-Pierre; Talbotec, Cécile; Colomb, Virginie; Ruemmele, Frank M; Goulet, Olivier

2011-04-01

Microvillous inclusion disease (MVID) is a rare congenital enterocyte disorder causing severe diarrhea and intestinal failure. The objective of this study was to analyze clinical evolution and the most frequent complications of MVID in children receiving parenteral nutrition (PN) and after small-bowel transplantation (SBTx) with the aim to improve treatment strategies and prognosis. From 1995 to 2009, 24 patients (16 boys, median follow-up 4.7 years, range: from birth to 23.5 years) with MVID were admitted to our unit. The recorded parameters included growth, neurological development, liver and renal functions, bone disease, and outcome. Almost half of the children were from consanguineous families from the Mediterranean area. All of the patients completely depended on PN. Four children died of PN complications before 4 years of age. Before or without SBTx, growth failure was common (mean height -2.5 standard deviations [SD]), as was developmental delay (12/24), liver (20/22 with fibrosis) or kidney disease (3/23 with moderate renal insufficiency), and osteoporosis (6/24). Thirteen children underwent SBTx (9 isolated, 4 combined with liver Tx) at a median age of 3.5 years. Follow-up after SBTx was 0.4 to 14 years. Patient survival rates were 63% without SBTx and 77% with SBTx. After SBTx, 4 children experienced catch-up growth. PN in MVID is difficult to manage and requires expertise. Despite improved results in expert centers, the risk of death or irreversible sequelae is higher with PN than after Tx. SBTx, despite being complicated, remains the only hope to improve the quality of life and long-term prognosis of these children.

Dose-response analysis of heavy metal toxicants in man. Direct in vivo assessment of body burden

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellis, K.J.

Differences in uptake, metabolism, and excretion of heavy metals makes selection of a suitable biological media as a monitor of body burden very difficult. Exposure assessments based on body fluid levels can provide, at best, only general population estimates. The most frequently monitored media are blood, urine, nail or hair clippings, sweat, and saliva. Unfortunately each of these tissues can be influenced by recent exposure conditions and are not accurate indices of the total dose or body burden. However, direct in vivo measurements of body burden in humans, have recently been performed. This nuclear technique has focused on the measurementsmore » of kidney and liver cadmium (Cd) by neutron activation analysis and bone lead (Pb) determinations using x-ray fluorescence. The dose-response relationship for renal dysfunction based on the direct in vivo body burden for Cd is presented. The most probable Cd value for the kidney associated with renal impairment is approximately 35 mg. Approximately 10% of the subjects with 20 mg Cd in the kidney will have moderately elevated ..beta../sub 2/-microglobulin, an early indicator of potential renal functional changes. 11 refs., 5 figs., 2 tabs.« less

Recent analytical approaches to detect exhaled breath ammonia with special reference to renal patients.

PubMed

Krishnan, Sanduru Thamarai; Devadhasan, Jasmine Pramila; Kim, Sanghyo

2017-01-01

The ammonia odor from the exhaled breath of renal patients is associated with high levels of blood urea nitrogen. Typically, in the liver, ammonia and ammonium ions are converted into urea through the urea cycle. In the case of renal dysfunction, urea is unable to be removed and that causes a buildup of excessive ammonia. As small molecules, ammonia and ammonium ions can be forced into the blood-lung barrier and occur in exhaled breath. Therefore, people with renal failure have an ammonia (fishy) odor in their exhaled breath. Thus, exhaled breath ammonia can be a potential biomarker for monitoring renal diseases during hemodialyis. In this review, we have summarized the source of ammonia in the breath of end-stage renal disease patient, cause of renal disorders, exhaled breath condensate, and breath sampling. Further, various biosensor approaches to detect exhaled ammonia from renal patients and other ammonia systems are also discussed. We conclude with future perspectives, namely colorimetric-based real-time breathing diagnosis of renal failure, which might be useful for prospective studies.

Recommendations for the proper use of nonprescription cough suppressants and expectorants in solid-organ transplant recipients.

PubMed

Gabardi, Steven; Carter, Danielle; Martin, Spencer; Roberts, Keri

2011-03-01

To describe the pharmacology and safety of oral over-the-counter cough suppressants and expectorants and to present recommendations for the use of these agents in solid-organ transplant recipients based on the potential for adverse drug reactions or drug-disease interactions. Data from journal articles and other sources describing the pharmacology and safety of over-the-counter cough suppressants and expectorants, drug-drug interactions with immunosuppressive agents, and drug-disease state interactions are reviewed. Potential and documented drug-drug interactions between immunosuppressive agents and over-the-counter cough medications guaifenesin, dextromethorphan, diphenhydramine, and codeine were evaluated on the basis of pharmacokinetic and pharmacodynamic principles. Interactions between these cough medications and the physiological changes in the body following transplantation also were examined. Diphenhydramine requires additional monitoring when used to treat cough in transplant recipients owing to its anticholinergic properties and the potential for interactions with cyclosporine. Dextromethorphan can be used in most transplant recipients, although greater caution should be exercised if the patient has undergone liver transplant or has liver impairment. Guaifenesin can be used in transplant recipients but should be used with caution in patients receiving kidney or lung transplants and in patients with renal impairment. Codeine combined with guaifenesin is another option for cough and can be used in most transplant patients although those with reduced renal function should be monitored carefully for adverse events.

Ameliorating effects of goby fish protein hydrolysates on high-fat-high-fructose diet-induced hyperglycemia, oxidative stress and deterioration of kidney function in rats.

PubMed

Nasri, Rim; Abdelhedi, Ola; Jemil, Ines; Daoued, Ines; Hamden, Khaled; Kallel, Choumous; Elfeki, Abdelfattah; Lamri-Senhadji, Myriem; Boualga, Ahmed; Nasri, Moncef; Karra-Châabouni, Maha

2015-12-05

This study investigated the therapeutic potential of undigested goby fish (Zosterisessor ophiocephalus) muscle proteins (UGP) and their hydrolysates on high-fat-high-fructose diet (HFFD)-fed rats. HFFD induced hyperglycemia, manifested by a significant increase in the levels of glucose and glycogen as well as α-amylase activity when compared to normal rats. The administration of GPHs to HFFD-fed rats significantly decreased α-amylase activity and the contents of blood glucose and hepatic glycogen. By contrast, the UGP increased the glucose metabolic disorders in HFFD-fed rats. Furthermore, HFFD-fed rats showed oxidative stress, as evidenced by decreased antioxidant enzyme activities and glutathione (GSH) levels and increased concentration of the lipid peroxidation product malondialdehyde in liver and kidney. Interestingly, the daily gavage of UGP and GPHs improved the redox status in liver and kidney of HFFD-rats by ameliorating or reversing the above-mentioned changes. Moreover, GPHs exhibited a renal protective role by reversing the HFFD-induced decease of uric acid and increase of creatinine levels in serum and preventing some HFFD-induced changes in kidney architecture. The results demonstrate that GPHs contain bioactive peptides that possess significant hypoglycemic and antioxidant properties, and ameliorate renal damage in rats fed hypercaloric diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

PubMed Central

Micanovic, Radmila; Chitteti, Brahmananda R.; Dagher, Pierre C.; Srour, Edward F.; Khan, Shehnaz; Hato, Takashi; Lyle, Allison; Tong, Yan; Wu, Xue-Ru

2015-01-01

Tamm-Horsfall protein (THP) is a glycoprotein uniquely expressed in the kidney. We recently showed an important role for THP in mediating tubular cross-talk in the outer medulla and in suppressing neutrophil infiltration after kidney injury. However, it remains unclear whether THP has a broader role in neutrophil homeostasis. In this study, we show that THP deficiency in mice increases the number of neutrophils, not only in the kidney but also in the circulation and in the liver, through enhanced granulopoiesis in the bone marrow. Using multiplex ELISA, we identified IL-17 as a key granulopoietic cytokine specifically upregulated in the kidneys but not in the liver of THP−/− mice. Indeed, neutralization of IL-17 in THP−/− mice completely reversed the systemic neutrophilia. Furthermore, IL-23 was also elevated in THP−/− kidneys. We performed real-time PCR on laser microdissected tubular segments and FACS-sorted renal immune cells and identified the S3 proximal segments, but not renal macrophages, as a major source of increased IL-23 synthesis. In conclusion, we show that THP deficiency stimulates proximal epithelial activation of the IL-23/IL-17 axis and systemic neutrophilia. Our findings provide evidence that the kidney epithelium in the outer medulla can regulate granulopoiesis. When this novel function is added to its known role in erythropoiesis, the kidney emerges as an important regulator of the hematopoietic system. PMID:25556169

Expression of cytochrome P-450 4 enzymes in the kidney and liver: regulation by PPAR and species-difference between rat and human.

PubMed

Ito, Osamu; Nakamura, Yasuhiro; Tan, Liping; Ishizuka, Tsuneo; Sasaki, Yuko; Minami, Naoyoshi; Kanazawa, Masayuki; Ito, Sadayoshi; Sasano, Hironobu; Kohzuki, Masahiro

2006-03-01

Members of the cytochrome P-450 4 (CYP4) family catalyze the omega-hydroxylation of fatty acids, and some of them have the PPAR response element in the promoter area of the genes. The localization of CYP4A and PPAR isoforms and the effect of PPAR agonists on CYP4A protein level and activity were determined in rat kidney and liver. Immunoblot analysis showed that CYP4A was expressed in the liver and proximal tubule, with lower expression in the preglomerular microvessel, glomerulus and thick ascending limb (TAL), but the expression was not detected in the collecting duct. PPARalpha was expressed in the liver, proximal tubule and TAL. PPARgamma was expressed in the collecting duct, with lower expression in the TAL, but no expression in the proximal tubule and liver. The PPARalpha agonist clofibrate induced CYP4A protein levels and activity in the renal cortex and liver. The PPARgamma agonist pioglitazone did not modulate them in these tissues. The localization of CYP4A and CYP4F were further determined in human kidney and liver by immunohistochemical technique. Immunostainings for CYP4A and CYP4F were observed in the hepatocytes of the liver lobule and the proximal tubules, with lower stainings in the TALs and collecting ducts, but no staining in the glomeruli or renal vasculatures. These results indicate that the inducibility of CYP4A by PPAR agonists in the rat tissues correlates with the expression of the respective PPAR isoforms, and that the localization of CYP4 in the kidney has a species-difference between rat and human.

[Lopinavir/ritonavir in patients with human immunodeficiency virus infection in special situations].

PubMed

Tasias, María; Aldeguer, José López

2014-11-01

Ritonavir-boosted lopinavir (LPV/r) is a protease inhibitor used for the treatment of human immunodeficiency virus (HIV) infection in both normal patients and in certain situations. In patients with renal failure, LPV/r does not require dosage adjustment because it is metabolized in the liver. Cohort studies have shown that the incidence of varying degrees of renal disease and/or crystalluria related to combination antiretroviral therapy with tenofovir and some protease inhibitors (PI) does not appear with LPV/r or that the incidence is much lower with this combination. Neurocognitive impairments are described in a high proportion of patients with HIV infection and viral replication or related inflammatory activity in the subarachnoid space. In these patients, LPV/r is one of the therapeutic options. A score has been published that rates antiretroviral drugs according to the concentration attained in the cerebrospinal fluid (CSF). LPV/r levels reached in CSF exceed the IC50 of wild-type HIV and has a valuable score (score 3) of the drugs currently used. The most important comorbid condition is chronic hepatitis, due to its frequency and because the biotransformation of LPV/r occurs in the liver. In these circumstances, it is important to evaluate the influence of liver failure on blood drug levels and how these values may cause liver toxicity. LPV/r dose modification has not been established in the presence of liver failure. LPV/r-induced liver toxicity has only been reported with a certain frequency when liver enzymes were elevated at baseline or in patients with chronic hepatitis C, although most cases of liver toxicity were mild. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality, acute cellular rejection, infections, and changes in the liver function tests while on caspofungin.

PubMed

Doria, Cataldo; Bodzin, Adam S; Vaccino, Silvia; Daskalakis, Constantine; Krawitz, Steven; Ramirez, Carlo B

2011-01-01

This study is a retrospective analysis of death, adverse events (AE), fungal infections, and hepatic function among recipients of liver transplantation at high risk of fungal infection who received prophylactic treatment with caspofungin. After reviewing data of 105 patients who had received isolated liver transplant between January 2003 and April 2007, we identified and analyzed 82 high-risk patients. Post-transplant patients at high risk for fungal infection are commonly defined by the presence of at least one of the following: (i) re-transplantation; (ii) re-operation; (iii) renal dysfunction. However, in our practice, patients are also considered at high risk for developing fungal infections if they present with the following: (iv) fever of unknown origin; (v) hypothermia; (vi) positive random culture for fungus at the time of transplant (bile and/or ascites); (vii) sepsis; (viii) use of vasopressors; (ix) re-intubation, during the first hospitalization after liver transplant; (x) prolonged intubation (>24 h), and (xi) acute respiratory distress syndrome, until negative fungal cultures are obtained. Exact conditional logistic regression was used to compare the risk of death, AEs, and fungal infections between patients who received caspofungin, other antifungal drugs, and no antifungal drugs. Analyses were then performed with SAS 9.1 (SAS Institute Inc., Cary, NC, USA). Patients were between 27 and 72 yr old (mean = 55), with two-thirds male and three-quarters Caucasian. Sixteen patients received caspofungin (11 preventively), and 32 received other antifungal (26 preventively). There were no proven fungal infections among the patients who received caspofungin, three infections among patients who received other antifungal (3/26 = 12%), and 14 infections among patients who were not preventively treated (14/45 = 31%). These infection rates were significantly different across the three groups (p = 0.029), with caspofungin and other antifungal preventive treatment comparable (p = 0.540), and both better than no preventive treatment at all (OR = 0.15, p = 0.049, for caspofungin versus no preventive treatment; OR = 0.29, p = 0.085, for other antifungal versus no preventive treatment). Caspofungin appears to be an effective preventive agent against fungal infections when used in recipients of liver transplant designated as high risk for fungal infection. Usage of caspofungin in these patients does not carry an apparent increase in risk of death or acute cellular rejection, although we observed a significantly higher risk of AEs, especially acute renal failure (p = 0.001), in patients who received this agent. © 2010 John Wiley & Sons A/S.

Liver Transplantation and Donor Body Mass Index >30: Use or Refuse?

PubMed

Andert, Anne; Becker, Niklas; Ulmer, Florian; Schöning, Wenzel; Hein, Marc; Rimek, Alexandra; Neumann, Ulf; Schmeding, Maximilian

2016-03-31

Organ shortage is a major problem in liver transplantation. The use of extended criteria donors has become the most important strategy for increasing the donor pool. However, the role of donor body mass index has not yet been thoroughly investigated. The aim of our study was to compare outcomes after liver transplantation in patients who received a liver from a donor with a BMI <30, 30-39, and ≥40, with special regard to the incidence of early allograft dysfunction (EAD) and primary non-function (PNF). One hundred and sixty-three patients who underwent liver transplantation at the University Hospital Aachen between June 2010 and January 2014 were included in this analysis. The outcome of liver transplantation was evaluated by the 30-day and 1-year patient and graft survival rates and the incidences of post-reperfusion syndrome (PRS), EAD, and PNF. The BMI 30-39 group had a higher incidence of EAD than the BMI <30 and BMI ≥40 groups. We observed 5 cases of PNF in the BMI <30 group. The incidence of acute renal failure was significantly higher in the BMI 30-39 and BMI ≥40 groups than in the BMI <30 group. Patient and graft survival did not differ significantly among the 3 groups. Based on the findings of this study, grafts from obese donors with a BMI >30 can be safely transplanted. Therefore, the donor pool can be enlarged to include such obese donors without a negative impact on the long-term patient outcome after liver transplantation.

Thymoglobulin induction in liver transplant recipients with a tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: a five-year randomized prospective study.

PubMed

Boillot, Olivier; Seket, Belhassen; Dumortier, Jérôme; Pittau, Gabriella; Boucaud, Catherine; Bouffard, Yves; Scoazec, Jean-Yves

2009-11-01

This randomized, comparative study assessed the long-term efficacy and tolerability of thymoglobulin (TMG) induction in 93 liver transplant patients with an initial regimen of tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids. Forty-four patients were randomly allocated to the TMG+ group, and 49 patients were randomly allocated to the TMG- group. In both groups, Tac was given orally at the initial daily dose of 0.075 mg/kg twice daily, and MMF was given at the initial daily dose of 2 g/day. Steroid withdrawal was planned at 3 months after liver transplantation. The results were evaluated with respect to acute rejection incidence, patient and graft survival, graft function, and medical complications until 5 years or death for all patients. No significant differences were found between groups for the incidence of acute rejection at 5 years (11.4% versus 14.3%), 5-year patient survival (77.3% versus 87.8%), graft function, or postoperative renal function. One patient in the TMG- group underwent retransplantation. There was no difference between groups with respect to the incidence of medical complications, excepted for a higher rate of leukopenia in the TMG+ group, during the 5-year follow-up. In conclusion, the results of this prospective randomized study suggest that the addition of TMG to a triple immunosuppressive regimen (Tac, MMF, and steroids) did not modify the incidence of acute rejection episodes or long-term survival and was responsible for increased leukopenia rates.

Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease.

PubMed

Fujimaru, T; Mori, T; Sekine, A; Mandai, S; Chiga, M; Kikuchi, H; Ando, F; Mori, Y; Nomura, N; Iimori, S; Naito, S; Okado, T; Rai, T; Hoshino, J; Ubara, Y; Uchida, S; Sohara, E

2018-07-01

Distinguishing autosomal-dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease-causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The kidney of chicken adapts to chronic metabolic acidosis: in vivo and in vitro studies.

PubMed

Craan, A G; Lemieux, G; Vinay, P; Gougoux, A

1982-08-01

Renal adaptation to chronic metabolic acidosis was studies in Arbor Acre hens receiving ammonium chloride by stomach tube 0.75 g/kg/day during 6 days. During a 14-day study, it was shown that the animals could excrete as much as 60% of the acid load during ammonium chloride administration. At the same time urate excretion fell markedly but the renal contribution to urate excretion (14%) did not change. During acidosis, blood glutamine increased twofold and the tissue concentration of glutamine rose in both liver and kidney. Infusion of L-glutamine led to increased ammonia excretion and more so in acidotic animals. Glutaminase I, glutamate dehydrogenase, alanine aminotransferase (GPT), and malic enzyme activities increased in the kidney during acidosis but phosphoenolpyruvate carboxykinase (PEPCK) activity did not change. Glutaminase I was not found in the liver, but hepatic glutamine synthetase rose markedly during acidosis. Glutamine synthetase was not found in the kidney. Renal tubules incubated with glutamine and alanine were ammoniagenic and gluconeogenic to the same degree as rat tubules with the same increments in acidosis. Lactate was gluconeogenic without increment during acidosis. The present study indicates that the avian kidney adapts to chronic metabolic acidosis with similarities and differences when compared to dog and rat. Glutamine originating from the liver appears to be the major ammoniagenic substrate. Our data also support the hypothesis that hepatic urate synthesis is decreased during acidosis.

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.

PubMed

Radha Krishna, Yellapu; Saraswat, Vivek Anand; Das, Khaunish; Himanshu, Goel; Yachha, Surender Kumar; Aggarwal, Rakesh; Choudhuri, Gour

2009-03-01

Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute-on-chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with this distinctive form of liver failure. ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti-hepatitis A virus (HAV)/anti-hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto-systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3-month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver-operating curves were plotted to measure performance of the present prognostic model, model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score. ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3+/-18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd-Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4+/-1.6 and mean MELD score was 28.6+/-9.06. Three-month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in 45 (34%), spontaneous bacterial peritonitis in 27 (20.5%), UGI bleeding in 15(11%) and hyponatraemia in 50 (41.3%). On univariate analysis, ascites, hepatic encephalopathy, renal failure, GI bleeding, total bilirubin, hyponatraemia and coagulopathy were significant predictors of mortality. Multivariate analysis revealed grades 3 and 4 HE [odds ratio (OR 32.1)], hyponatraemia (OR 9.2) and renal failure (OR 16.8) as significant predictors of 3-month mortality and a prognostic model using these predictors was constructed. Areas under the curve for the present predicted prognostic model, MELD, and CTP were 0.952, 0.941 and 0.636 respectively. ACLF due to hepatitis A or E super infection results in significant short-term mortality. The predictors of ominous outcome include grades 3 and 4 encephalopathy, hyponatraemia and renal failure. Present prognostic model and MELD scoring system were better predictors of 3-month outcome than CTP score in these patients. Early recognition of those with dismal prognosis may permit timely use of liver replacement/supportive therapies.

Tissue gadolinium deposition in renally impaired rats exposed to different gadolinium-based MRI contrast agents: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

PubMed

Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Kanki, Akihiko; Watanabe, Shigeru; Nishimura, Hirotake; Tanimoto, Daigo; Higashi, Hiroki; Yamamoto, Akira

2013-10-01

To quantify tissue gadolinium (Gd) deposition in renally impaired rats exposed to Gd-EOB-DTPA and other Gd-based MRI contrast agents by means of inductively coupled plasma mass spectrometry (ICP-MS), and to compare the differences in distribution among major organs as possible triggers for nephrogenic systemic fibrosis (NSF). A total of 15 renally impaired rats were injected with Gd-EOB-DTPA, Gd-DTPA-BMA and Gd-HP-DO3A. Gd contents of skin, liver, kidney, lung, heart, spleen, diaphragm and femoral muscle were measured by inductively coupled plasma mass spectrometry (ICP-MS). Histological assessment was also conducted. Tissue Gd deposition in all organs was significantly higher (P=0.005~0.009) in the Gd-DTPA-BMA group than in the Gd-HP-DO3A and Gd-EOB-DTPA groups. In the Gd-DTPA-BMA group, Gd was predominantly deposited in kidney (1306±605.7μg/g), followed by skin, liver, lung, spleen, femoral muscle, diaphragm and heart. Comparing Gd-HP-DO3A and Gd-EOB-DTPA groups, Gd depositions in the kidney, liver and lung were significantly lower (P=0.009~0.011) in the Gd-EOB-DTPA group than in the Gd-HP-DO3A group although no significant differences were seen for any other organs. Gd-EOB-DTPA is a stable and safe Gd-based contrast agent (GBCA) showing lower Gd deposition in major organs in renally impaired rats, compared with other GBCAs. This fact suggests that the risk of NSF onset would be low in the use of Gd-EOB-DTPA. Copyright © 2013 Elsevier Inc. All rights reserved.

The sodium phosphate cotransporter family and nicotinamide phosphoribosyltransferase contribute to the daily oscillation of plasma inorganic phosphate concentration.

PubMed

Miyagawa, Atsumi; Tatsumi, Sawako; Takahama, Wako; Fujii, Osamu; Nagamoto, Kenta; Kinoshita, Emi; Nomura, Kengo; Ikuta, Kayo; Fujii, Toru; Hanazaki, Ai; Kaneko, Ichiro; Segawa, Hiroko; Miyamoto, Ken-Ichi

2018-05-01

Circulating inorganic phosphate exhibits a remarkable daily oscillation based on food intake. In humans and rodents, the daily oscillation in response to food intake may be coordinated to control the intestinal absorption, renal excretion, cellular shifts, and extracellular concentration of inorganic phosphate. However, mechanisms regulating the resulting oscillation are unknown. Here we investigated the roles of the sodium phosphate cotransporter SLC34 (Npt2) family and nicotinamide phosphoribosyltransferase (Nampt) in the daily oscillation of plasma inorganic phosphate levels. First, it is roughly linked to urinary inorganic phosphate excretion. Second, expression of renal Npt2a and Npt2c, and intestinal Npt2b proteins also exhibit a dynamic daily oscillation. Analyses of Npt2a, Npt2b, and Npt2c knockout mice revealed the importance of renal inorganic phosphate reabsorption and cellular inorganic phosphate shifts in the daily oscillation. Third, experiments in which nicotinamide and a specific Nampt inhibitor (FK866) were administered in the active and rest phases revealed that the Nampt/NAD + system is involved in renal inorganic phosphate excretion. Additionally, for cellular shifts, liver-specific Nampt deletion disturbed the daily oscillation of plasma phosphate during the rest but not the active phase. In systemic Nampt +/- mice, NAD levels were significantly reduced in the liver, kidney, and intestine, and the daily oscillation (active and rest phases) of the plasma phosphate concentration was attenuated. Thus, the Nampt/NAD + system for Npt2 regulation and cellular shifts to tissues such as the liver play an important role in generating daily oscillation of plasma inorganic phosphate levels. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Peripheral Blood Eosinophilia and Hypersensitivity Reactions among Patients Receiving Outpatient Parenteral Antibiotics

PubMed Central

Blumenthal, Kimberly G.; Youngster, Ilan; Rabideau, Dustin J.; Parker, Robert A.; Manning, Karen S.; Walensky, Rochelle P.; Nelson, Sandra B.

2015-01-01

Background While drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications. Objective We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs). Methods We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least one differential blood count. We used multivariate Cox proportional hazards models, with time-varying antibiotic treatment indicators, to assess the impact of demographic data and antibiotic exposures on eosinophilia and subsequent HSR, including documented rash, renal injury, and liver injury. Possible Drug Rash Eosinophilia and Systemic Symptoms (DRESS) syndrome cases were identified and manually validated. Results Of 824 patients (60% male, median age 60 years, median therapy duration 41 days), 210 (25%) developed eosinophilia with median peak absolute eosinophil count of 726/mL [IQR: 594–990/mL]. Use of vancomycin, penicillin, rifampin, and linezolid were associated with a higher hazard of developing eosinophilia. There was subsequent HSR in 64/210 (30%) patients with eosinophilia, including rash (N=32), renal injury (N=31), and liver injury (N=13). Patients with eosinophilia were significantly more likely to develop rash (HR = 4.16 [2.54, 6.83]; p<0.0001) and renal injury (HR = 2.13 [1.36, 3.33]; p=0.0009), but not liver injury (HR = 1.75 [0.92, 3.33]; p=0.09). Possible DRESS syndrome occurred in 7/824 (0.8%) patients; 4 (57%) were on vancomycin. Conclusions Drug-induced eosinophilia is common with parenteral antibiotics. While most patients with eosinophilia do not develop an HSR, eosinophilia increases the hazard rate of developing rash and renal injury. DRESS syndrome was more common than previously described. PMID:25981739

Diethylene glycol-induced toxicities show marked threshold dose response in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landry, Greg M., E-mail: Landry.Greg@mayo.edu; Dunning, Cody L., E-mail: cdunni@lsuhsc.edu; Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu

Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUNmore » and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.« less

The influence of acclimation temperature on the lipid composition of the larval lamprey, Petromyzon marinus, depends on tissue and lipid class.

PubMed

Kao, Yung-Hsi; Sheridan, Mark A; Holmes, John A; Youson, John H

2010-11-01

This study was designed to examine the effect of thermal acclimation on the lipid composition of fat depot organs the liver and kidneys of larval sea lamprey, Petromyzon marinus. We found that 21 °C-acclimated larvae possessed lower total lipid amounts in the liver (39% lower) and kidneys (30% lower) than 13 °C-acclimated larvae. Relatively lower lipid contents in the liver and kidneys of 21 °C-acclimated lamprey primarily resulted from a reduction in stored lipid reserve, triacylglycerol, but not the structural lipid, phospholipid. Compared to 21 °C-acclimated larvae, 13 °C-acclimated larvae were found to possess fewer saturated fatty acids (SFAs) and more unsaturated fatty acids (USFAs) in renal triacylglycerol and phospholipid classes, while there were no significant differences in the SFAs and USFAs of hepatic triacylglycerol, phospholipid, cholesteryl ester, fatty acid, and monoacylglycerol classes. Fewer SFAs, found in the kidney triacylglycerol of 13 °C-acclimated lamprey, were due to lower 12:0 and 14:0 fatty acids, but those in the renal phospholipid class were characterized by fewer 14:0, 15:0, and 16:0 fatty acids. More USFAs in renal triacylglycerol, as indicated by a higher unsaturation index, primarily resulted from higher polyunsaturated fatty acids (18:2ω6, 18:3ω3, and 18:4ω3); whereas, in the renal phospholipid class, this was a result of higher monoenes (18:1, 20:1, and 22:1ω9) and ω3 polyunsaturated fatty acids (18:4ω3). These data suggest that the influence of thermal acclimation on the lipid composition of lamprey fat depot organs depends on tissue and lipid class.

Clinical and Virological Outcome of European Patients Infected With HIV

ClinicalTrials.gov

2018-04-26

HIV; Hepatitis B; Hepatitis C; AIDS; Coinfection; Cardiovascular Diseases; Diabetes Mellitus; Acidosis, Lactic; Renal Insufficiency; Fractures, Bone; End Stage Liver Disease; Kidney Failure, Chronic; Proteinuria

The prevalence and implications of BK virus replication in non-renal solid organ transplant recipients: A systematic review.

PubMed

Viswesh, Velliyur; Yost, Sarah E; Kaplan, Bruce

2015-07-01

The significance of BK viruria and viremia in non-renal solid organ transplants is poorly understood. A systematic review was performed reviewing the incidence and implications of BK virus replication in non-renal solid organ transplants. Ninety-seven studies were identified, of which 18 including lung, heart, liver and pancreas transplants were included. The overall incidence of BK viruria and viremia was 20% and 3% respectively and 17 cases of BK nephropathy were identified. Heart transplant recipients had a higher overall incidence of BK viremia than other non-renal organ types, and the majority of cases of BK virus-associated nephropathy were in heart transplant recipients. The incidence of BK viremia was significantly lower in non-renal solid organ transplants than that of renal transplant recipients and BK virus-associated nephropathy was rare. BK virus-associated nephropathy may be considered in heart transplant recipients who have unexplained and persistent renal dysfunction not attributable to other causes. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamic contrast-enhanced magnetic resonance imaging of abdominal solid organ and major vessel: comparison of enhancement effect between Gd-EOB-DTPA and Gd-DTPA.

PubMed

Tamada, Tsutomu; Ito, Katsuyoshi; Sone, Teruki; Yamamoto, Akira; Yoshida, Koji; Kakuba, Koki; Tanimoto, Daigo; Higashi, Hiroki; Yamashita, Takenori

2009-03-01

To evaluate the differences in enhancement of the abdominal solid organ and the major vessel on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) obtained with gadolinium ethoxybenzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA: EOB) and gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) in the same patients. A total of 13 healthy volunteers underwent repeat assessments of abdominal MR examinations with DCE-MRI using either Gd-DTPA at a dose of 0.1 mmol/kg body weight or EOB at a dose of 0.025 mmol/kg body weight. DCE images were obtained at precontrast injection and in the arterial phase (AP: 25 seconds), portal phase (PP: 70 seconds), and equilibrium phase (EP: 3 minutes). The signal intensities (SIs) of liver at AP, PP, and EP; the SIs of spleen, renal cortex, renal medulla, pancreas, adrenal gland, aorta at AP; and the SIs of portal vein and inferior vena cava (IVC) at PP were defined using region-of-interest measurements, and were used for calculation of signal intensity ratio (SIR). The mean SIRs of liver (0.195+/-0.140), spleen (1.35+/-0.353), renal cortex (1.58+/-0.517), renal medulla (0.548+/-0.259), pancreas (0.540+/-0.183), adrenal gland (1.04+/-0.405), and aorta (2.44+/-0.648) at AP as well as the mean SIRs of portal vein (1.85+/-0.477) and IVC (1.16+/-0.187) at PP in the EOB images were significantly lower than those (0.337+/-0.200, 1.99+/-0.443, 2.01+/-0.474, 0.742+/-0.336, 0.771+/-0.227, 1.26+/-0.442, 3.22+/-1.20, 2.73+/-0.429, and 1.68+/-0.366, respectively) in the Gd-DTPA images (P<0.05 each). There was no significant difference in mean SIR of liver at PP between EOB (0.529+/-0.124) and Gd-DTPA (0.564+/-0.139). Conversely, the mean SIR of liver at EP was significantly higher with EOB (0.576+/-0.167) than with Gd-DTPA (0.396+/-0.093) (P<0.001). Lower arterial vascular and parenchymal enhancement with Gd-EOB, as compared with Gd-DTPA, may require reassessment of its dose, despite the higher late venous phase liver parenchymal enhancement. Copyright (c) 2009 Wiley-Liss, Inc.

Evaluation of haematological, hepatic and renal functions of petroleum tanker drivers in Lagos, Nigeria.

PubMed

Awodele, Olufunsho; Sulayman, Ademola A; Akintonwa, Alade

2014-03-01

Hydrocarbons which are among the major components of petroleum products are considered toxic and have been implicated in a number of human diseases. Tanker drivers are continuously exposed to hydrocarbons by inhalation and most of these drivers do not use protective devices to prevent inhalation of petroleum products; nor do they visit hospital regularly for routine check-up. In view of this occupational hazard, we investigated the haematological, renal and hepatic functions of workers of petroleum tankers drivers in Lagos, Nigeria. Twenty-five tanker drivers' and fifteen control subjects were randomly selected based on the selection criteria of not smoking and working for minimum of 5 years as petroleum tanker driver. The liver, renal and haematological parameters were analyzed using automated clinical and haematological analyzers while the lipid peroxidation and antioxidant level tests were assayed using standard methods. There were significant (p ≤ 0.05) increases in the levels of serum alanine amino transferase (31.14±13.72; 22.38±9.89), albumin (42.50±4.69; 45.36±1.74) and alkaline phosphatase (84.04±21.89; 62.04±23.33) of petroleum tanker drivers compared with the controls. A significant (p≤0.05) increase in the levels of creatinine, urea and white blood cells of the tanker drivers, compared with the controls, were also obtained. The results have enormous health implications of continuous exposure to petroleum products reflected hepatic and renal damage of petroleum tanker drivers. Therefore, there is need for this group of workers to be sensitized on the importance of protective devises, regular medical checkup and management.

Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).

PubMed

Sato, Tomohiro; Tamada, Tsutomu; Watanabe, Shigeru; Nishimura, Hirotake; Kanki, Akihiko; Noda, Yasufumi; Higaki, Atsushi; Yamamoto, Akira; Ito, Katsuyoshi

2015-06-01

This study was undertaken to quantify tissue gadolinium (Gd) deposition in hepatorenally impaired rats exposed to gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of inductively coupled plasma mass spectrometry (ICP-MS) and to compare differences in Gd distribution among major organs as possible triggers for nephrogenic systemic fibrosis. Five hepatorenally impaired rats (5/6-nephrectomized, with carbon-tetrachloride-induced liver fibrosis) were injected with Gd-EOB-DTPA. Histological assessment was conducted and Gd content of the skin, liver, kidneys, lungs, heart, spleen, diaphragm, and femoral muscle was measured by inductively coupled plasma mass spectrometry (ICP-MS) at 7 days after last injection. In addition, five renally impaired rats were injected with Gd-EOB-DTPA and the degree of tissue Gd deposition was compared with that in the hepatorenally impaired rats. ICP-MS analysis revealed significantly higher Gd deposition in the kidneys, spleen, and liver (p = 0.009-0.047) in the hepatorenally impaired group (42.6 ± 20.1, 17.2 ± 6.1, 8.4 ± 3.2 μg/g, respectively) than in the renally impaired group (17.2 ± 7.7, 5.4 ± 2.1, 2.8 ± 0.7 μg/g, respectively); no significant difference was found for other organs. In the hepatorenally impaired group, Gd was predominantly deposited in the kidneys, followed by the spleen, liver, lungs, skin, heart, diaphragm, and femoral muscle. Histopathological investigation revealed hepatic fibrosis in the hepatorenally impaired group. Compared with renally impaired rats, tissue Gd deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA was significantly increased in the kidneys, spleen, and liver, probably due to the impairment of the dual excretion pathways of the urinary and biliary systems.

Risk factors and outcomes of acute kidney injury in patients with acute liver failure.

PubMed

Tujios, Shannan R; Hynan, Linda S; Vazquez, Miguel A; Larson, Anne M; Seremba, Emmanuel; Sanders, Corron M; Lee, William M

2015-02-01

Patients with acute liver failure (ALF) frequently develop renal dysfunction, yet its overall incidence and outcomes have not been fully assessed. We investigated the incidence of acute kidney injury (AKI) among patients with ALF, using defined criteria to identify risk factors and to evaluate its effect on overall outcomes. We performed a retrospective review of data from 1604 patients enrolled in the Acute Liver Failure Study Group, from 1998 through 2010. Patients were classified by the Acute Kidney Injury Network criteria, as well as for etiology of liver failure (acetaminophen-based, ischemic, and all others). Seventy percent of patients with ALF developed AKI, and 30% received renal replacement therapy (RRT). Patients with severe AKI had higher international normalized ratio values than those without renal dysfunction (P < .001), and a higher proportion had advanced-grade coma (coma grades 3 or 4; P < .001) or presented with hypotension requiring vasopressor therapy (P < .001). A greater proportion of patients with acetaminophen-induced ALF had severe kidney injury than of patients with other etiologies of ALF; 34% required RRT, compared with 25% of patients with ALF not associated with acetaminophen or ischemia (P < .002). Of the patients with ALF who were alive at 3 weeks after study entry, significantly fewer with AKI survived for 1 year. Although AKI reduced the overall survival time, more than 50% of patients with acetaminophen-associated or ischemic ALF survived without liver transplantation (even with RRT), compared with 19% of patients with ALF attribute to other causes (P < .001). Only 4% of patients requiring RRT became dependent on dialysis. Based on a retrospective analysis of data from more than 1600 patients, AKI is common in patients with ALF and affects short- and long-term outcomes, but rarely results in chronic kidney disease. Acetaminophen-induced kidney injury is frequent, but patients have better outcomes than those with other forms of ALF. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

PubMed

Berenguer, Juan; Rodríguez-Castellano, Elena; Carrero, Ana; Von Wichmann, Miguel A; Montero, Marta; Galindo, María J; Mallolas, Josep; Crespo, Manuel; Téllez, María J; Quereda, Carmen; Sanz, José; Barros, Carlos; Tural, Cristina; Santos, Ignacio; Pulido, Federico; Guardiola, Josep M; Rubio, Rafael; Ortega, Enrique; Montes, María L; Jusdado, Juan J; Gaspar, Gabriel; Esteban, Herminia; Bellón, José M; González-García, Juan

2017-08-01

We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4 + T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Chylous ascites in a cheetah (Acinonyx jubatus) with venoocclusive liver disease.

PubMed

Terrell, Scott P; Fontenot, Deidre K; Miller, Michele A; Weber, Martha A

2003-12-01

An 11-yr-old female cheetah (Acinonyx jubatus) was diagnosed clinically with hepatic and renal disease and euthanatized after an extended illness. Postmortem examination revealed 8-10 L of milky white fluid in the abdominal cavity and markedly dilated lymphatic vessels within the intestinal mesentery. The abdominal fluid was a chylous effusion based on the cytologic predominance of lymphocytes and macrophages and comparison of cholesterol and triglyceride levels in the fluid and in serum. Gross and histopathologic lesions in the liver were consistent with a diagnosis of venoocclusive liver disease. Chylous ascites is uncommon with human chronic liver disease and is rarely identified in animals.

Association of Transcatheter Aortic Valve Replacement With 30-Day Renal Function and 1-Year Outcomes Among Patients Presenting With Compromised Baseline Renal Function: Experience From the PARTNER 1 Trial and Registry.

PubMed

Beohar, Nirat; Doshi, Darshan; Thourani, Vinod; Jensen, Hanna; Kodali, Susheel; Zhang, Feifan; Zhang, Yiran; Davidson, Charles; McCarthy, Patrick; Mack, Michael; Kapadia, Samir; Leon, Martin; Kirtane, Ajay

2017-07-01

The frequency of baseline renal impairment among high-risk and inoperable patients with severe aortic stenosis undergoing a transcatheter aortic valve replacement (TAVR) and the effect of TAVR on subsequent renal function are, to our knowledge, unknown. To determine the effect of TAVR among patients with baseline renal impairment. This substudy of patients with baseline renal impairment (estimated glomerular filtration rate [eGFR] ≤ 60 mL/min) and paired baseline and 30-day measures of renal function undergoing TAVR in the PARTNER 1 trial and continued access registries was conducted in 25 centers in the United States and Canada. Patients were categorized with improved eGFR (30-day follow-up eGFR≥10% higher than baseline pre-TAVR), worsened eGFR (≥10% lower), or no change in renal function (neither). Baseline characteristics, 30-day to 1-year all-cause mortality, and repeat hospitalization were compared. Multivariable models were constructed to identify predictors of 1-year mortality and of improvement/worsening in eGFR. Of the 821 participants, 401 (48.8%) were women and the mean (SD) age for participants with improved, unchanged, or worsening eGFR was 84.90 (6.91) years, 84.37 (7.13) years, and 85.39 (6.40) years, respectively. The eGFR was 60 mL/min or lower among 821 patients (72%), of whom 345 (42%) improved, 196 (24%) worsened, and 280 (34%) had no change at 30 days. There were no differences in baseline age, body mass index, diabetes, chronic obstructive pulmonary disease, coronary artery disease, peripheral arterial disease, hypertension, pulmonary hypertension, renal or liver disease, New York Heart Association III/IV symptoms, transaortic gradient, left ventricular ejection fraction, or procedural characteristics. The group with improved eGFR had more women, nonsmokers, and a lower cardiac index. Those with worsening eGFR had a higher median Society of Thoracic Surgeons score and left ventricle mass. From 30 days to 1 year, those with improved eGFR had no difference in mortality or repeat hospitalization. Those with worsening eGFR had increased mortality (25.5% vs 19.1%, P = .07) but no significant increases in repeat hospitalization or dialysis. Predictors of improved eGFR were being female (odds ratio [OR], 1.38; 95% CI, 1.03-1.85; P = .03) and nonsmoking status (OR, 1.49; 95% CI, 1.11-1.01; P = .01); predictors of worsening eGFR were baseline left ventricle mass (OR, 1.00; 95% CI, 1.00-1.01; P = .01), smoking (OR, 1.51; 95% CI, 1.06-2.14; P = .02), and age (OR, 1.03; 95% CI, 1.00-1.05; P = .05); and predictors of 1-year mortality were baseline left ventricular ejection fraction (OR, 0.98; 95% CI, 0.97-0.99; P = .003), baseline eGFR (OR, 0.98; 95% CI, 0.96-0.99; P < .001), and worsening eGFR vs no change in eGFR (OR, 1.51; 95% CI, 1.02-2.24; P = .04). Baseline renal impairment was frequent among patients who underwent TAVR. While improved eGFR did not improve 1-year outcomes, worsening eGFR was associated with increased mortality. clinicaltrials.gov Identifier: NCT00530894.

Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity

PubMed Central

Giani, Jorge F.; Eriguchi, Masahiro; Bernstein, Ellen A.; Katsumata, Makoto; Shen, Xiao Z.; Li, Liang; McDonough, Alicia A.; Fuchs, Sebastien; Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.

2017-01-01

Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension. PMID:27988209

Fever, thrombocytopenia, and AKI-A profile of malaria, dengue, and leptospirosis with renal failure in a South Indian tertiary-care hospital.

PubMed

Prabhu, Mayoor V; S, Arun; Ramesh, Venkat

In the tropics, the triad of fever, thrombocytopenia, and AKI portends a grim prognosis with high mortality and a severe strain on already-stretched resources. Malaria, dengue, and leptospirosis account for most cases. We undertook a review of cases to determine factors accounting for adverse prognosis. All patients presenting to the emergency room (ER) with a history of fever, thrombocytopenia, and renal failure were included in the study. Patients were followed until discharge or death, and end points looked at were 1-week and 30-day mortality, and renal function upon discharge. Parameters like liver function test (LFT), renal function, and platelet count upon discharge were also documented. A total of 43 patients was included in the study. Mean age was 42.5 years with 86% males. Mean APACHE and SOFA scores on admission were 23.89 and 15.42, respectively. Mean admission platelet counts were 41,000. Mean serum creatinine was 4.1, and bilirubin was 9.94. A platelet count of < 34,000, serum creatinine of > 4, albumin of > 2.3, SOFA score of > 20, and APACHE score of > 32.2 were significantly predictive of 1 week mortality. Need for mechanical ventilation, oliguria on admission, and need for dialysis all were highly predictive of 30-day mortality. In addition, a serum bicarbonate of < 12, INR of > 1.5, hemoglobin of < 9.5 were highly predictive of higher 30 day mortality. Overall, 1-week mortality was 16.3%, of which 48% was accounted for by patients with leptospirosis. Factors like low platelet count, oliguria, need for dialysis, high APACHE and SOFA scores on admission, need for mechanical ventilation, and low serum albumin portend a grave prognosis. There is need for randomized control trials (RCT) to further determine adverse prognostic factors in this subsect of patients.

X-ray attenuation of the liver and kidney in cats considered at varying risk of hepatic lipidosis.

PubMed

Lam, Richard; Niessen, Stijn J; Lamb, Christopher R

2014-01-01

X-ray attenuation of the liver has been measured using computed tomography (CT) and reported to decrease in cats with experimentally induced hepatic lipidosis. To assess the clinical utility of this technique, medical records and noncontrast CT scans of a series of cats were retrospectively reviewed. A total of 112 cats met inclusion criteria and were stratified into three hepatic lipidosis risk groups. Group 1 cats were considered low-risk based on no history of inappetence or weight loss, and normal serum chemistry values; Group 2 cats were considered intermediate risk based on weight loss, serum hepatic enzymes above normal limits, or reasonably controlled diabetes mellitus; and Group 3 cats were considered high risk based on poorly controlled diabetes mellitus due to hypersomatotropism. Mean CT attenuation values (Hounsfield units, HU) were measured using regions of interest placed within the liver and cranial pole of the right kidney. Hepatic and renal attenuation were weakly positively correlated with each other (r = 0.2, P = 0.03) and weakly negatively correlated with body weight (r = -0.21, P = 0.05, and r = -0.34, P = 0.001, respectively). Mean (SD) hepatic and renal cortical attenuation values were 70.7 (8.7) HU and 49.6 (9.2) HU for Group 1 cats, 71.4 (7.9) HU and 48.6 (9.1) HU for Group 2, and 68.9 (7.6) HU and 47.6 (7.2) HU for Group 3. There were no significant differences in hepatic or renal attenuation among groups. Findings indicated that CT measures of X-ray attenuation in the liver and kidney may not be accurate predictors of naturally occurring hepatic lipidosis in cats. © 2013 American College of Veterinary Radiology.

[Hepatic amyloidosis as cause of severe intrahepatic cholestasis].

PubMed

Gavilán, J C; Bermúdez, F J; Márquez, A; Sánchez-Carrillo, J J; González-Santos, P

2003-01-01

The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.

Inappropriate Prescription and Renal Function Among Older Patients with Cognitive Impairment.

PubMed

Sönnerstam, Eva; Sjölander, Maria; Gustafsson, Maria

2016-12-01

Older people are more sensitive to drugs and adverse drug reactions than younger people because of age-related physiological changes such as impaired renal function. As people with dementia are particularly vulnerable to the effects of drugs, it is especially important to evaluate the dosages of renally cleared medications in this group. The aim of this study was to estimate the prevalence of impaired renal function and inappropriate prescriptions on the basis of renal function among older patients with dementia or cognitive impairment. The medical records of 428 patients aged ≥65 years who were admitted to two hospitals in northern Sweden were reviewed and renally cleared medications were identified. The Cockcroft-Gault equation was used to evaluate renal function. Doses were evaluated according to the Geriatric Dosage Handbook. Renal function was impaired (estimated glomerular filtration rate <60 ml/min) in 65.4 % of the study population. Impaired renal function was associated with increasing age. Among 547 prescriptions identified as renally cleared medications, 9.1 % were inappropriate based on the patient's renal function; 13.5 % of the 326 patients prescribed renally cleared medications had inappropriate prescriptions. Inappropriate prescriptions were more common among patients living in nursing homes. Impaired renal function is common and inappropriate prescription is prevalent among old people with cognitive impairment in northern Sweden. Continuous consideration of renal function is important when prescribing medications to this group.

Microsomal and Cytosolic Scaling Factors in Dog and Human Kidney Cortex and Application for In Vitro-In Vivo Extrapolation of Renal Metabolic Clearance

PubMed Central

Scotcher, Daniel; Billington, Sarah; Brown, Jay; Jones, Christopher R.; Brown, Colin D. A.; Rostami-Hodjegan, Amin

2017-01-01

In vitro-in vivo extrapolation of drug metabolism data obtained in enriched preparations of subcellular fractions rely on robust estimates of physiologically relevant scaling factors for the prediction of clearance in vivo. The purpose of the current study was to measure the microsomal and cytosolic protein per gram of kidney (MPPGK and CPPGK) in dog and human kidney cortex using appropriate protein recovery marker and evaluate functional activity of human cortex microsomes. Cytochrome P450 (CYP) content and glucose-6-phosphatase (G6Pase) activity were used as microsomal protein markers, whereas glutathione-S-transferase activity was a cytosolic marker. Functional activity of human microsomal samples was assessed by measuring mycophenolic acid glucuronidation. MPPGK was 33.9 and 44.0 mg/g in dog kidney cortex, and 41.1 and 63.6 mg/g in dog liver (n = 17), using P450 content and G6Pase activity, respectively. No trends were noted between kidney, liver, and intestinal scalars from the same animals. Species differences were evident, as human MPPGK and CPPGK were 26.2 and 53.3 mg/g in kidney cortex (n = 38), respectively. MPPGK was 2-fold greater than the commonly used in vitro-in vivo extrapolation scalar; this difference was attributed mainly to tissue source (mixed kidney regions versus cortex). Robust human MPPGK and CPPGK scalars were measured for the first time. The work emphasized the importance of regional differences (cortex versus whole kidney–specific MPPGK, tissue weight, and blood flow) and a need to account for these to improve assessment of renal metabolic clearance and its extrapolation to in vivo. PMID:28270564

Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice

PubMed Central

Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi

2016-01-01

In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. PMID:26755155

Clinical application of calculated split renal volume using computed tomography-based renal volumetry after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic acid renal scan data.

PubMed

Lee, Chan Ho; Park, Young Joo; Ku, Ja Yoon; Ha, Hong Koo

2017-06-01

To evaluate the clinical application of computed tomography-based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium-99m dimercaptosuccinic acid renal scan. The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The renal cortical volume of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate and split renal volume calculated using this renal cortical volume were compared with the split renal function measured with technetium-99m dimercaptosuccinic acid renal scan. A strong correlation between split renal function and split renal volume of the tumor-bearing kidney was observed before and after surgery (r = 0.89, P < 0.001 and r = 0.94, P < 0.001). The preoperative and postoperative split estimated glomerular filtration rate of the operated kidney showed a moderate correlation with split renal function (r = 0.39, P = 0.004 and r = 0.49, P < 0.001). The correlation between reductions in split renal function and split renal volume of the operated kidney (r = 0.87, P < 0.001) was stronger than that between split renal function and percent reduction in split estimated glomerular filtration rate (r = 0.64, P < 0.001). The split renal volume calculated using computed tomography-based renal volumetry had a strong correlation with the split renal function measured using technetium-99m dimercaptosuccinic acid renal scan. Computed tomography-based split renal volume measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney. © 2017 The Japanese Urological Association.

Multidisciplinary Inpatient Palliative Care Intervention

ClinicalTrials.gov

2006-05-12

Cerebrovascular Accident; Cancer; Coronary Arteriosclerosis; Heart Failure, Congestive; Diabetes Mellitus; Acquired Immunodeficiency Syndrome; Failure to Thrive; Pulmonary Disease, Chronic Obstructive; Dementia; Kidney Failure, Chronic; Pneumonia; Liver Failure; Renal Failure; Respiratory Failure; Stroke

[Acute renal failure in the transretinoic syndrome].

PubMed

Sastre, A; Gago, E; Baños, M; Gómez, E

2007-01-01

The all-trans retinoic acid (ATRA) is the treatment of first line of acute promyelocytic leukemia (APL). ATRA is usually well tolerated, but a few major side effects can be observed, ATRA syndrome (RAS) being the most important of them, potentially fatal. The manifestations of this Syndrome are fever, weight gain, pulmonary infiltrates, pleural or pericardial effusions, hypotension, liver dysfunction and renal failure. We studied to the 29 patients diagnosed in (January of 2002 - December of 2004) of acute promyelocytic leukemia (APL), which were treated with ATRA, all received the 45 dose of mg/m(2)/d . The diagnosis of the leukemia was made by citomorphologist analysis. The criterion of renal insufficiency, it was an increase of the creatinina superior to 20% of the basal level. The definition of the transretinoico acid Syndrome was based on the clinical criteria of Frankel. Fourteen patients presented the Transretinoico Syndrome (48.3%), 11 of which (37.9%) died. The fundamental differences between the patients with or without ATRA were: fever (14 vs. 9, p=0,017), gain of weight (14 vs 0, p=0,000), pleural effusion (14 vs 2, p=0.000), pulmonary infiltrates (13 vs 1, p=0,000), cardiac failure (12 versus 2, p=0,000), respiratory distress (12 versus 4, p=0,003), presence of renal failure (10 vs 4, p=0,02), necessity of substitute renal treatment (6 vs 0, p=0,006) and arterial hypotension (12 vs. 3, p=0,001). The acute renal failure appeared in 10 of the 14 patients with SAR (71.4%), to 12+/-5 (1-25) days of the beginning of the treatment and their duration it was of 14+/-5 (1-46) days. Six (60%) needed substitute renal treatment and 5 (50%) died. Of the patients who survived, only a patient continues in dialysis. In both patient in that renal biopsy was made, the study showed signs of cortical necrosis. The appearance of acute renal failure in the course of the SAR is frequent, being observed deterioration of the renal function that needs substitute renal treatment in more than half the cases. The association of RAS with renal failure entails the high mortality (50%). The diagnosis and the precocious restoration of suitable the preventive measures and therapeutic are very important to avoid in possible the this serious complication of the treatment with ATRA.

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

The effect of anatomic differences on the relationship between renal artery and diaphragmatic crus.

PubMed

Esen, K; Tok, S; Balci, Yuksel; Apaydin, F D; Kara, E; Uzmansel, D

2018-01-01

The aim of this study is to investigate the effect of anatomic differences on the relationship between renal artery and diaphragmatic crus via the touch of two structures. The study included dynamic computed tomography (CT) scans of 308 patients performed mainly for characterisation of liver and renal masses. Anatomic differences including the thickness of the diaphragmatic crus, the localisation of renal artery ostium at the wall of aorta, the level of renal artery origin with respect to superior mesenteric artery were evaluated. Statistical relationships between renal artery-diaphragmatic crus contact and the anatomic differences were assessed. Thickness of the diaphragmatic crus at the level of renal artery origin exhibited a statistically significant relationship to renal artery-diaphragmatic crus contact at the left (p < 0.001) and right side (p < 0.001). There was a statistically significant relationship between high renal artery origin and renal artery- -diaphragmatic crus contact at the left (p < 0.001) and right side (p = 0.01). The localisation of renal artery ostium at the wall of aorta (right side, p = 0.436, left side, p = 0.681) did not demonstrate a relationship to renal artery-diaphragmatic crus contact. Thickness of the diaphragmatic crus and high renal artery origin with respect to superior mesenteric artery are crucial anatomic differences determining the relationship of renal artery and diaphragmatic crus. (Folia Morphol 2018; 77, 1: 22-28).

Pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small cell lung cancer and chronic renal failure who are undergoing hemodialysis.

PubMed

Togashi, Yosuke; Masago, Katsuhiro; Fukudo, Masahide; Terada, Tomohiro; Ikemi, Yasuaki; Kim, Young Hak; Fujita, Shiro; Irisa, Kaoru; Sakamori, Yuichi; Mio, Tadashi; Inui, Ken-Ichi; Mishima, Michiaki

2010-05-01

Although erlotinib, an orally active and selective tyrosine kinase inhibitor of epidermal growth factor receptor, is mainly metabolized in the liver, its effectiveness and safety for patients with chronic renal failure (CRF) undergoing hemodialysis (HD) has not been reported. Thus, we investigated the pharmacokinetics (PK) of erlotinib and its active metabolite OSI-420 in such patients with nonsmall cell lung cancer (NSCLC). We administered 150 mg erlotinib daily to three patients with NSCLC and CRF undergoing HD (HD group) and five patients with NSCLC and normal organ function (control group) and analyzed the PK of erlotinib and OSI-420. In the HD group, PK analyses were performed on day 1 (off HD), day 8 (off HD), and day 9 (on HD) after starting administration of erlotinib, and in the control group, they were performed on day 1 and day 8. In the HD group, there were little differences in the PK data between day 8 and day 9. The PK data on day 1 and day 8 of the HD group were also similar to those of the control group. There were no serious adverse events in any cases, and one of the HD patients achieved partial response. Erlotinib was hardly affected by renal function and HD, which confirms the effectiveness and safety of erlotinib treatment in patients with NSCLC and CRF undergoing HD. Erlotinib can become one treatment option for such patients.

Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with Ureteropelvic Junction Obstruction.

PubMed

Li, Xiao-Dong; Wu, Yu-Peng; Wei, Yong; Chen, Shao-Hao; Zheng, Qing-Shui; Cai, Hai; Xue, Xue-Yi; Xu, Ning

2018-01-01

This study aimed to identify factors predicting the recoverability of renal function after pyeloplasty in adult patients with ureteropelvic junction obstruction. We retrospectively reviewed 138 adults with unilateral renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was classified preoperatively according to the Society for Fetal Urology (SFU) grading system. All patients underwent Doppler ultrasonography, excretory urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic acid radioisotope (99mTc DTPA) renography before and after surgery. Renal resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12 months. Multivariate analysis identified age, renal pelvic type, SFU grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis area ratio (PHAR) as independent predictors of renal function recoverability after pyeloplasty. However, preoperative RRI and RRI decline were not significantly associated with recoverability of renal function in patients aged >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU grade, and extrarenal pelvis were associated with greater improvements in postoperative renal function. Preoperative differential renal function cannot independently predict the recoverability of postoperative renal function in adult patients with unilateral renal obstruction-induced hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline in RRI were significantly associated with the recoverability of renal function in adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR were significantly associated with renal function recoverability in patients aged ≥35 years. Renal function recovery was better in patients younger than 35 years when compared with older patients. © 2018 S. Karger AG, Basel.

Renal dopamine containing nerves. What is their functional significance?

PubMed

DiBona, G F

1990-06-01

Biochemical and morphological studies indicate that there are nerves within the kidney that contain dopamine and that various structures within the kidney contain dopamine receptors. However, the functional significance of these renal dopamine containing nerves in relation to renal dopamine receptors is unknown. The functional significance could be defined by demonstrating that an alteration in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves is dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors. Thus, the hypothesis becomes: reflex or electrical activation of efferent renal nerves causes alterations in renal function (eg, renal blood flow, water and solute handling) that are inhibited by specific and selective dopamine receptor antagonists. As reviewed herein, the published experimental data do not support the hypothesis. Therefore, the view that alterations in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves are dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors remains unproven.

Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry.

PubMed

Mekahli, Djalila; van Stralen, Karlijn J; Bonthuis, Marjolein; Jager, Kitty J; Balat, Ayşe; Benetti, Elisa; Godefroid, Nathalie; Edvardsson, Vidar O; Heaf, James G; Jankauskiene, Augustina; Kerecuk, Larissa; Marinova, Svetlana; Puteo, Flora; Seeman, Tomas; Zurowska, Aleksandra; Pirenne, Jacques; Schaefer, Franz; Groothoff, Jaap W

2016-11-01

The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these children, adolescents, and young adults. Cohort study. We derived data for children, adolescents, and young adults with ARPKD with either kidney or combined liver-kidney transplants for 1995 to 2012 from the ESPN/ERA-EDTA Registry, a European pediatric renal registry collecting data from 36 European countries. Liver transplantation. Transplantation and patient survival. 202 patients with ARPKD aged 19 years or younger underwent transplantation after a median of 0.4 (IQR, 0.0-1.4) years on dialysis therapy at a median age of 9.0 (IQR, 4.1-13.7) years. 32 (15.8%) underwent combined liver-kidney transplantation, 163 (80.7%) underwent kidney transplantation, and 7 (3.5%) were excluded because transplantation type was unknown. Age- and sex-adjusted 5-year patient survival posttransplantation was 95.5% (95% CI, 92.4%-98.8%) overall: 97.4% (95% CI, 94.9%-100.0%) for patients with kidney transplantation in contrast to 87.0% (95% CI, 75.8%-99.8%) with combined liver-kidney transplantation. The age- and sex-adjusted risk for death after combined liver-kidney transplantation was 6.7-fold (95% CI, 1.8- to 25.4-fold) greater than after kidney transplantation (P=0.005). Five-year death-censored kidney transplant survival following combined liver-kidney and kidney transplantation was similar (92.1% vs 85.9%; P=0.4). No data for liver disease of kidney therapy recipients. Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. Long-term follow-up of both kidney and liver involvement are needed to better delineate the optimal transplantation strategy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Changes of Tight Junction Protein Claudins in Small Intestine and Kidney Tissues of Mice Fed a DDC Diet.

PubMed

Abiko, Yukie; Kojima, Takashi; Murata, Masaki; Tsujiwaki, Mitsuhiro; Takeuchi, Masaya; Sawada, Norimasa; Mori, Michio

2013-12-01

DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine)-fed mice are widely used as a model for cholestatic liver disease. We examined the expression of tight junction protein claudin subspecies by immunofluorescent histochemistry in small intestine and kidney tissues of mice fed a DDC diet for 12 weeks. In the small intestine, decreases in claudin-3, claudin-7 and claudin-15 were observed in villous epithelial cells corresponding to the severity of histological changes while leaving the abundance of these claudin subspecies unchanged in crypt cells. Nevertheless, the proliferative activity of intestinal crypt cells measured by immunohistochemistry for Ki-67 decreased in the mice fed the DDC diet compared with that of control mice. These results suggest the possibility that DDC feeding affects the barrier function of villous epithelial cells and thus inhibits the proliferative activity of crypt epithelial cells. On the other hand, in the kidney, remarkable changes were found in the subcellular localization of claudin subspecies in a segment-specific manner, although histological changes of renal epithelial cells were quite minimal. These results indicate that immunohistochemistry for claudin subspecies can serve as a useful tool for detecting minute functional alterations of intestinal and renal epithelial cells.

The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.

PubMed

Albawardi, Alia; Almarzooqi, Saeeda; Saraswathiamma, Dhanya; Abdul-Kader, Hidaya Mohammed; Souid, Abdul-Kader; Alfazari, Ali S

2015-01-01

The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors. It measured the effects of commonly used immunosuppressants (sirolimus-rapamycin, tacrolimus, and cyclosporine) on cellular respiration in target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target of rapamycin (mTOR), a serine/ threonine kinase that supports nutrient-dependent cell growth and survival, is known to control energy conversion processes within the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune®) have been shown to impair mitochondrial function. Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent lymphokine production leading to a reduced T-cell function. Sirolimus (10 μM) inhibited renal (22%, P=0.002), hepatic (39%, P<0.001), and cardiac (42%, P=0.005) cellular respiration. Tacrolimus and cyclosporine had no or minimum effects on cellular respiration in these tissues. Thus, these results clearly demonstrate that impaired cellular respiration (bioenergetics) is a sensitive biomarker of the immunosuppressants that target mTOR.

Inferior long-term outcomes of liver-kidney transplantation using donation after cardiac death donors: single-center and organ procurement and transplantation network analyses.

PubMed

Wadei, Hani M; Bulatao, Ilynn G; Gonwa, Thomas A; Mai, Martin L; Prendergast, Mary; Keaveny, Andrew P; Rosser, Barry G; Taner, C Burcin

2014-06-01

Limited data are available for outcomes of simultaneous liver-kidney (SLK) transplantation using donation after cardiac death (DCD) donors. The outcomes of 12 DCD-SLK transplants and 54 SLK transplants using donation after brain death (DBD) donors were retrospectively compared. The baseline demographics were similar for the DCD-SLK and DBD-SLK groups except for the higher liver donor risk index for the DCD-SLK group (1.8 ± 0.4 versus 1.3 ± 0.4, P = 0.001). The rates of surgical complications and graft rejections within 1 year were comparable for the DCD-SLK and DBD-SLK groups. Delayed renal graft function was twice as common in the DCD-SLK group. At 1 year, the serum creatinine levels and the iothalamate glomerular filtration rates were similar for the groups. The patient, liver graft, and kidney graft survival rates at 1 year were comparable for the groups (83.3%, 75.0%, and 82.5% for the DCD-SLK group and 92.4%, 92.4%, and 92.6% for the DBD-SLK group, P = 0.3 for all). The DCD-SLK group had worse patient, liver graft, and kidney graft survival at 3 years (62.5%, 62.5%, and 58.9% versus 90.5%, 90.5%, and 90.6%, P = 0.03 for all) and at 5 years (62.5%, 62.5%, and 58.9% versus 87.4%, 87.4%, and 87.7%, P < 0.05 for all). An analysis of the Organ Procurement and Transplantation Network database showed inferior 1- and 5-year patient and graft survival rates for DCD-SLK patients versus DBD-SLK patients. In conclusion, despite comparable rates of surgical and medical complications and comparable kidney function at 1 year, DCD-SLK transplantation was associated with inferior long-term survival in comparison with DBD-SLK transplantation. © 2014 American Association for the Study of Liver Diseases.

Pancreas Transplantation: Solid Organ and Islet

PubMed Central

Mittal, Shruti; Johnson, Paul; Friend, Peter

2014-01-01

Transplantation of the pancreas, either as a solid organ or as isolated islets of Langerhans, is indicated in a small proportion of patients with insulin-dependent diabetes in whom severe complications develop, particularly severe glycemic instability and progressive secondary complications (usually renal failure). The potential to reverse diabetes has to be balanced against the morbidity of long-term immunosuppression. For a patient with renal failure, the treatment of choice is often a simultaneous transplant of the pancreas and kidney (SPK), whereas for a patient with glycemic instability, specifically hypoglycemic unawareness, the choice between a solid organ and an islet transplant has to be individual to the patient. Results of SPK transplantation are comparable to other solid-organ transplants (kidney, liver, heart) and there is evidence of improved quality of life and life expectancy, but the results of solitary pancreas transplantation and islets are inferior with respect to graft survival. There is some evidence of benefit with respect to the progression of secondary diabetic complications in patients with functioning transplants for several years. PMID:24616200

Creation of a solid organ transplant program in an underdeveloped country: Mexico's General Hospital transplantation program.

PubMed

García Covarrubias, L; Rossano García, A; Cicero Lebrija, A; Luque Hernández, A; Hinojosa Heredia, H; Fernández Ángel, D; Córdova, J; García Covarrubias, A; Bautista Olayo, R; Diliz Perez, H S

2013-05-01

With a population of >112 million persons, all Mexicans are entitled to receive medical care by the state and more than half have limited access to healthcare. From January 1985 to March 2009, 40 renal transplants were performed from living donors with a high percentage of complications. In April 2009, a new Solid Organ Transplantation Program was started; herein, we present this enterprise to the international community and briefly present a perspective on the Mexican transplant situation. We performed a retrospective chart review of kidney and liver transplant recipients from April 2009 to November 2011, including demographic features, immunosuppression, complications as well as initial and 1 month function. We performed 68 kidney (59 living and 9 deceased donors) and 5 liver transplants (cadaveric donors). The kidney transplant recipients were 73.5% males and showed an overall mean age of 29.77 years (range, 18-60). The donor mean age was 34.08 years. Mean recipient creatinine pretransplant was 13.32 mg/dL, while at day 5 it was 2.33 and at month one, 1.32 mg/dL. Five grafts were lost (7.3%): 4 due to death with a functioning graft and 1 due to acute pyelonephritis. Five patients experienced delayed graft function Basiliximab induction was required in all but one who received thymoglobulin owing to a high panel reactive antibody. Maintenance therapy included a calcineurin inhibitor, mycophenolate mofetil (MMF), and prednisone. Liver transplant recipients were 83.6% women. The etiologies were alcoholic cirrhosis (n = 2), primary billiary cirrhosis (n = 1) and hepatitis C virus infection (n = 2). Complications included: reperfusion syndrome (n = 1), convulsive crisis (medication; n = 1), acute respiratory distress syndrome (n = 1), and death (n = 1). Their Model for End-Stage Liver Disease scopes were 10-21. After basiliximab induction, they had maintenance therapy with tacrolimus, MMF, and steroids. The donor mean age was 26.2 years. All survivors show normal liver function tests currently. From 1985 to 2009, 40 kidney transplants were performed, with multiple complications including donor deaths. Our current results were comparable to international standards, with <15% complication rate. Copyright © 2013 Elsevier Inc. All rights reserved.

Perioperative Characteristics of Siblings Undergoing Liver or Kidney Transplant.

PubMed

Ersoy, Zeynep; Ozdemirkan, Aycan; Pirat, Arash; Torgay, Adnan; Arslan, Gulnaz; Haberal, Mehmet

2015-11-01

Reasons for chronic liver and kidney failure may vary; sometimes more than 1 family member may be affected, and may require a transplant. The aim of this study was to examine the similarities or differences between the perioperative characteristics of siblings undergoing liver or kidney transplant. The medical records of 6 pairs of siblings who underwent liver transplant and 4 pairs of siblings who underwent kidney transplant at Baskent University Hospital between 1989 and 2014 were retrospectively analyzed. Collected data included demographic features; comorbidities; reasons for liver and kidney failure; perioperative laboratory values; intraoperative hemodynamic parameters; use and volume of crystalloids, colloids, blood products, cell saver system, and albumin; duration of anesthesia; urine output; and postoperative follow-up data. The mean age of the 6 sibling pairs who underwent liver transplant was 16.3 ± 12.2 years. All 12 patients had Child-Pugh grade B cirrhosis, with mean disease duration of 7.8 ± 3.9 years. There were no significant differences between siblings with respect to intraoperative blood product transfusion, crystalloid and colloid fluid replacements, hypotension frequency, blood gas analyses, urinary output, duration of anhepatic phase, inotropic agent administration, postoperative laboratory values, need for mechanical ventilation and vasopressors, occurrence of acute renal failure and infections, and duration intensive care unit stay (P > .05). The mean age of the 4 sibling pairs who underwent kidney transplant was 21.3 ± 6.4 years, with mean duration of renal insufficiency of 2.2 ± 1.6 years. There were no significant differences between siblings with respect to intraoperative crystalloid and colloid fluid administration, duration of anesthesia, intraoperative mannitol and furosemide administration, and postoperative laboratory values (P > .05). In conclusion, the 6 sibling pairs who underwent liver transplant and 4 sibling pairs who underwent kidney transplant in our cohort had similar perioperative characteristics.

Reducing Disparities in the Quality of Advance Care Planning for Older Adults

ClinicalTrials.gov

2018-05-07

Metastatic Cancer; Congestive Heart Failure; Chronic Obstructive Pulmonary Disease; Parkinson Disease; Interstitial Lung Disease; Amyotrophic Lateral Sclerosis; End Stage Liver Disease; End Stage Renal Disease; Diabetes Complications

Reduction of systemic exposure and toxicity of cisplatin by encapsulation in poly-lactide-co-glycolide.

PubMed

Verrijk, R; Smolders, I J; Bosnie, N; Begg, A C

1992-12-01

The tissue distribution and normal tissue toxicity of cisplatin (cDDP) administered as poly-lactide-co-glycolide (PLAGA) microspheres, developed for loco-regional administration of cDDP to the liver, were studied in Wag/Rij rats. Venoportal administration of this formulation resulted in a reduction in total systemic and renal toxicity, which correlated with a decrease in normal tissue exposure to cDDP while maintaining high liver platinum levels. Liver-to-kidney platinum level ratios were 28 times higher after 4 h and 19 times higher after 24 h with PLAGA-cDDP microspheres than with free cDDP. Liver-to-blood platinum ratios at these times were 38 times and 36 times higher using PLAGA-cDDP. In a CC531 colon carcinoma liver micrometastases model, cytotoxicity of microsphere-released cDDP was confirmed in vivo by equal inhibition of tumor growth by PLAGA-cDDP and free cDDP over a period of 26 days. Free cDDP, however, caused significantly more histological renal damage and total body weight loss. The results were supported by the finding of higher plasma creatinine and urea concentrations 26 days after administration of free cDDP. Kidney platinum levels were 7 times lower when PLAGA-cDDP was used. These findings indicate a sparing effect on normal tissues when cDDP is targeted to the liver by formulation in PLAGA. PLAGA-cDDP microspheres may, therefore, be a useful and effective addition to current techniques of loco-regional chemotherapy for disseminated hepatic tumors.

Association between pulmonary function and renal function: findings from China and Australia.

PubMed

Yu, Dahai; Chen, Tao; Cai, Yamei; Zhao, Zhanzheng; Simmons, David

2017-05-01

The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function. Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m 2 were used as outcome. eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively. In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics).

[Strategies for a greater supply of organs for transplantation].

PubMed

Gridelli, B; Perico, N; Remuzzi, G

2001-01-01

The number of recipients waiting for a solid organ transplantation has increased greatly in the past 5 years. The supply of donor organs during this period has not kept pace, resulting in a large shortage of suitable organs. In an effort to overcome the disparity between supply of donor and demands, various strategies have emerged to expand the existing donor selection criteria. Kidneys from very old donors can be used successfully when a pre-transplant biopsy shows a modest degree of glomerular injury. Kidneys from donors of 50 years or more, or with a history of hypertension and diabetes, or other evidence of renal disease, currently not accepted for single' kidney transplantation, provide excellent function when transplanted together. In contrast, one liver can be enough for two patients. Split-liver transplantation, i.e. sharing one liver between an adult and a pediatric recipient, is becoming routine procedure and has the potential for meeting the need for liver replacement among children without interfering with adult waiting list. Splitting the liver for transplantation in two adults is a further step forward in the more efficient use of hepatic grafts from cadaver donors. Adult-to-adult living donor liver transplantation can further alleviate the pressure in the waiting list, but the risk for the donor must not be underestimated. The decrease in the number of heart-lung transplants in favour of more single and double lung transplants has also made more hearts and more lungs available. It is difficult to quantify the impact of all these procedures on the shortage of organ donors, but the waiting list should be cut by at least one-third for kidney and may be more for liver and lung transplants.

Clinical and laboratory aspects of Legionnaire's disease.

PubMed

Strampfer, M J; Cunha, B A

1987-12-01

Legionnaires' disease is an illness with protean manifestations that are due to infection with Legionella pneumophila. It occurs both in epidemic and sporadic form and usually presents as an atypical pneumonia. Relative bradycardia, abnormal liver function test results, and a patient presenting with an atypical pneumonia should alert the clinician to the possibility of Legionella. The presence of systemic involvement, specifically neurological, gastrointestinal, and renal abnormalities, should further suggest the diagnosis. Patients may demonstrate multiple extrapulmonary manifestations of legionnaires' disease, sometimes without pneumonia. Several methods are available to aid the clinician in making the diagnosis of legionnaires' disease, and the use of all tests will increase the overall sensitivity.

Outcome of tyrosinaemia type III.

PubMed

Ellaway, C J; Holme, E; Standing, S; Preece, M A; Green, A; Ploechl, E; Ugarte, M; Trefz, F K; Leonard, J V

2001-12-01

Tyrosinaemia type III is a rare disorder caused by a deficiency of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the catabolic pathway of tyrosine. The majority of the nine previously reported patients have presented with neurological symptoms after the neonatal period, while others detected by neonatal screening have been asymptomatic. All have had normal liver and renal function and none has skin or eye abnormalities. A further four patients with tyrosinaemia type III are described. It is not clear whether a strict low tyrosine diet alters the natural history of tyrosinaemia type III, although there remains a suspicion that treatment may be important, at least in infancy.

Nitrogen and sulphur mustard induced histopathological observations in mouse visceral organs.

PubMed

Sharma, Manoj; Pant, S C; Pant, J C; Vijayaraghavan, R

2010-11-01

Nitrogen mustards (HN) and sulphur mustard (SM) are potent alkylating blister inducing chemical warfare agents. Single 1.0 LD50 dose produced a progressive fall in body weight from second day onwards in all groups of mustard agents exposed animals. Histological examination of spleen, liver skin and kidney revealed significant histopathological lesions in nitrogen mustards and sulphur mustard. These lesions include granulovascular degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. The maximum toxic manifestation were noted in spleen and skin of HN-3 exposed mice while sulphur mustard reported maximum toxicity in liver and kidneys. The study suggests both nitrogen mustards and sulphur mustard to be extremely toxic by percutaneous route based on histopathological observation and can contributed to earlier reported free radical generation by these toxicants.

Effect of N-acetylarginine, a metabolite accumulated in hyperargininemia, on parameters of oxidative stress in rats: protective role of vitamins and L-NAME.

PubMed

Sasso, Simone; Dalmedico, Leticia; Delwing-Dal Magro, Débora; Wyse, Angela T S; Delwing-de Lima, Daniela

2014-08-01

In the present investigation, we initially evaluated the in vitro effect of N-acetylarginine on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of rats. Results showed that N-acetylarginine, at a concentration of 5.0 μM, decreased the activity of CAT in erythrocytes, enhanced TBA-RS in the renal cortex, decreased CAT and SOD activities in the renal medulla and decreased CAT and increased SOD and GSH-Px activities in the liver of 60-day-old rats. Furthermore, we tested the influence of the antioxidants, trolox and ascorbic acid, as well as of the N(ω) -nitro-L-arginine methyl ester (L-NAME) on the effects elicited by N-acetylarginine on the parameters tested. Antioxidants and L-NAME prevented most of the alterations caused by N-acetylarginine on the oxidative stress parameters evaluated. Data indicate that oxidative stress induction is probably mediated by the generation of NO and/or ONOO(-) and other free radicals because L-NAME and antioxidants prevented the effects caused by N-acetylarginine in the blood, renal tissues and liver of rats. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by N-acetylarginine. Copyright © 2014 John Wiley & Sons, Ltd.

Abernethy malformation associated with Caroli's syndrome in a patient with a PKHD1 mutation: a case report.

PubMed

Mi, Xiao-Xiao; Li, Xiao-Guang; Wang, Zi-Rong; Lin, Ling; Xu, Chun-Hai; Shi, Jun-Ping

2017-08-16

Abernethy malformation is a rare congenital anomaly characterised by the partial or complete absence of the portal vein and the subsequent development of an extrahepatic portosystemic shunt. Caroli's disease is a rare congenital condition characterised by non-obstructive saccular intrahepatic bile duct dilation. Caroli's disease combined with congenital hepatic fibrosis and/or renal cystic disease is referred to - Caroli's syndrome. The combination of Abernethy malformation and Caroli's syndrome has not been reported previously. We present the case of a 23-year-old female who was found to have both type II Abernethy malformation and Caroli's syndrome. Radiological imaging was performed, including computed tomography with three-dimensional reconstruction and magnetic resonance imaging with (magnetic resonance cholangiopancreatography (MRCP), which revealed a side-to-side portocaval shunt, intrahepatic bile duct dilation, congenital hepatic fibrosis, and renal cysts. In addition, PKHD1 (polycystic kidney and hepatic disease 1) gene mutational analysis revealed a paternally inherited heterozygous missense mutation (c.1877A > G, p.Lys626Arg). A liver biopsy confirmed the pathological features of Caroli's syndrome. To our knowledge, this is the first reported case of a patient with both type II Abernethy malformation and Caroli's syndrome diagnosed using a comprehensive approach that included imaging, mutational analysis, and liver biopsy. Additionally, this is the second reported case to date of an Asian patient presenting with liver and renal disorders with the same paternally inherited PKHD1 missense mutation.

Renal Function Descriptors in Neonates: Which Creatinine-Based Formula Best Describes Vancomycin Clearance?

PubMed

Bhongsatiern, Jiraganya; Stockmann, Chris; Yu, Tian; Constance, Jonathan E; Moorthy, Ganesh; Spigarelli, Michael G; Desai, Pankaj B; Sherwin, Catherine M T

2016-05-01

Growth and maturational changes have been identified as significant covariates in describing variability in clearance of renally excreted drugs such as vancomycin. Because of immaturity of clearance mechanisms, quantification of renal function in neonates is of importance. Several serum creatinine (SCr)-based renal function descriptors have been developed in adults and children, but none are selectively derived for neonates. This review summarizes development of the neonatal kidney and discusses assessment of the renal function regarding estimation of glomerular filtration rate using renal function descriptors. Furthermore, identification of the renal function descriptors that best describe the variability of vancomycin clearance was performed in a sample study of a septic neonatal cohort. Population pharmacokinetic models were developed applying a combination of age-weight, renal function descriptors, or SCr alone. In addition to age and weight, SCr or renal function descriptors significantly reduced variability of vancomycin clearance. The population pharmacokinetic models with Léger and modified Schwartz formulas were selected as the optimal final models, although the other renal function descriptors and SCr provided reasonably good fit to the data, suggesting further evaluation of the final models using external data sets and cross validation. The present study supports incorporation of renal function descriptors in the estimation of vancomycin clearance in neonates. © 2015, The American College of Clinical Pharmacology.

Therapeutic Potential of Traditional Chinese Medicine on Inflammatory Diseases

PubMed Central

Tsai, Wen-Hsin; Yang, Chih-Ching; Li, Ping-Chia; Chen, Wang-Chuan; Chien, Chiang-Ting

2013-01-01

Increased oxidative stress induces inflammation to several tissues/organs leading to cell death and long-term injury. Traditional Chinese Medicine (TCM) with antioxidant, anti-inflammatory, anti-apoptotic, and autophagic regulatory functions has been widely used as preventive or therapeutic strategy in modern medicine. Oxidative stress and inflammation have been widely reported to contribute to cigarette smoke-induced lung inflammation, hepatotoxicity, or sympathetic activation-induced liver inflammation, lipopolysaccharide-induced renal inflammation, and substance P-mediated neurogenic hyperactive bladder based on clinical findings. In this review, we introduce several evidences for TCM treatment including Monascus adlay (MA) produced by inoculating adlay (Cois lachrymal-jobi L. var. ma-yuen Stapf) with Monascus purpureus on lung injury, Amla (Emblica officinalis Gaertn. of Euphorbiaceae family) on hepatotoxin-induced liver inflammation, Virgate Wormwood Decoction (Yīn Chén Hāo tāng) and its active component genipin on sympathetic activation–induced liver inflammation, and green tea extract and its active components, catechins, or a modified TCM formula Five Stranguries Powder (Wǔ Lén Sǎn) plus Crataegi Fructus (Shān Zhā) on hyperactive bladder. The pathophysiologic and molecular mechanisms of TCM on ameliorating inflammatory diseases are discussed in the review. PMID:24716170

Health status and renal function evaluation of kidney vendors: a report from Pakistan.

PubMed

Naqvi, S A A; Rizvi, S A H; Zafar, M N; Ahmed, E; Ali, B; Mehmood, K; Awan, M J; Mubarak, B; Mazhar, F

2008-07-01

Unrelated kidney transplants have lead to commerce and kidney vending in Pakistan. This study on 104 vendors reports demographics, history, physical and systemic examination, ultrasound findings, renal and liver function and GFR by Cockcroft-Gault. Results were compared with 184 age, sex and nephrectomy duration matched living-related donors controls. Comparison of vendors versus controls showed mean age of 30.55 +/- 8.1 versus 30.65 +/- 7.85 (p = 0.91) years, M:F of 4.5:1 versus 4.2:1 and nephrectomy period of 33.89 +/- 30 versus 32.01 +/- 29.71 (p = 0.60) months respectively. Of the vendors 67% were bonded laborers earning <50 $/month as compared to controls where 68% were skilled laborers and self-employed earning >100 $/month. History of vendors revealed jaundice in 8%, stone disease in 2% and urinary tract symptoms in 4.8%. Postnephrectomy findings between vendors versus donors showed BMI of 21.02 +/- 2.8 versus 23.02 +/- 4.2 (p = 0.0001), hypertension in 17% versus 9.2% (p = 0.04), serum creatinine (mg/dL) of 1.17+/-0.21 versus 1.02 +/- 0.27 (p = 0.0001), GFR (mL/min) of 70.94 +/- 14.2 versus 95.4 +/- 20.44 (p = 0.0001), urine protein/creatinine of 0.150 +/- 0.109 versus 0.10 +/- 0.10 (p = 0.0001), hepatitis C positivity in 27% versus 1.0% (p = 0.0001) and hepatitis B positive 5.7% versus 0.5% (p = 0.04), respectively. In conclusion, vendors had compromised renal function suggesting inferior selection and high risk for developing chronic kidney disease in long term.

Death with functioning graft in living donor kidney transplantation: analysis of risk factors.

PubMed

El-Agroudy, Amgad E; Bakr, Mohamed A; Shehab El-Dein, Ahmed B; Ghoneim, Mohamed A

2003-01-01

Death with a functioning graft (DWF) has been reported as a major cause of graft loss after renal transplantation. It has been reported to occur in 9-30%. From March 1976 to January 2002, a total of 1400 living donor renal transplants were performed in our center. Out of 257 reported deaths among our patients, 131 recipients died with functioning grafts after a mean period of 53.4 +/- 53.2 months. DWF patients account for 27% of all graft losses in our series. The mean age was 34.9 + 10.6 (range 8-62 years), 98 of them were male and 33 were female. The original kidney disease was GN in 9, PN in 24, PCK in 5 and nephrosclerosis in 8 patients. Acute rejection episodes were diagnosed in 84 patients (63.1). The post-transplant complications encountered were hypertension in 78 patients (59.5%), diabetes mellitus in 30 patients (22.9%), medical infections in 68 (51.5%), hepatic complications in 30 (22.9%) and malignancy in 17 patients (13%). The main causes of death in these patients were infections in 46 (35.6%), cardiovascular in 23 (17.6%), liver cell failure in 15 patients (11.4%) and malignancy in 8 (6.1%). The mean serum creatinine was 2 +/- 0.6 mg/dl at last follow-up before death. We conclude that the relatively higher mortality in renal transplantation is, in part, due to co-morbid medical illness, pre-transplant dialysis treatment, and factors uniquely related to transplantation, including immunosuppression and other drug effects. DWF must be in consideration when calculating graft survival. Copyright 2003 S. Karger AG, Basel

Assessment of the relationship between renal volume and renal function after minimally-invasive partial nephrectomy: the role of computed tomography and nuclear renal scan.

PubMed

Bertolo, Riccardo; Fiori, Cristian; Piramide, Federico; Amparore, Daniele; Barrera, Monica; Sardo, Diego; Veltri, Andrea; Porpiglia, Francesco

2018-05-14

To evaluate the correlation between the loss of renal function as assessed by Tc99MAG-3 renal scan and the loss of renal volume as calculated by volumetric assessment on CT-scan in patients who underwent minimally-invasive partial nephrectomy (PN). PN prospectively-maintained database was retrospectively queried for patients who underwent minimally-invasive PN (2012-2017) for renal mass

Urinary Biomarkers for Screening for Renal Scarring in Children with Febrile Urinary Tract Infection: Pilot Study.

PubMed

Kitao, Tetsuya; Kimata, Takahisa; Yamanouchi, Sohsaku; Kato, Shogo; Tsuji, Shoji; Kaneko, Kazunari

2015-09-01

Recurrent febrile urinary tract infections during infancy cause renal scarring, which is characterized by progressive focal interstitial fibrosis and may lead to renal failure. Renal scarring can be diagnosed through scintigraphy, although it seems impractical to perform renal scintigraphy for all infants with febrile urinary tract infections. Therefore, it is important to search for a biomarker to identify the presence of renal scarring. We hypothesized that urinary biomarkers of nephropathy may increase in infants with renal scarring following febrile urinary tract infections. A total of 49 infants who underwent renal scintigraphy for febrile urinary tract infections were enrolled in the study. Several measurements were performed using urine samples, including total proteins, beta2-microglobulins, N-acetyl-β-D-glucosaminidase, neutrophil gelatinase associated lipocalin, liver-type fatty acid binding protein and angiotensinogen. Values were corrected by creatinine and compared between patients with and without renal scarring. Among urinary biomarkers only angiotensinogen in patients with scarring (median 14.6 μg/gm creatinine) demonstrated significantly higher levels than in patients without scarring (3.6 μg/gm creatinine, p <0.001). Urinary angiotensinogen may be useful for diagnosing the presence of renal scarring. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Application of a Physiologically Based Pharmacokinetic Model to Assess Propofol Hepatic and Renal Glucuronidation in Isolation: Utility of In Vitro and In Vivo Data

PubMed Central

Gill, Katherine L.; Gertz, Michael; Houston, J. Brian

2013-01-01

A physiologically based pharmacokinetic (PBPK) modeling approach was used to assess the prediction accuracy of propofol hepatic and extrahepatic metabolic clearance and to address previously reported underprediction of in vivo clearance based on static in vitro–in vivo extrapolation methods. The predictive capacity of propofol intrinsic clearance data (CLint) obtained in human hepatocytes and liver and kidney microsomes was assessed using the PBPK model developed in MATLAB software. Microsomal data obtained by both substrate depletion and metabolite formation methods and in the presence of 2% bovine serum albumin were considered in the analysis. Incorporation of hepatic and renal in vitro metabolic clearance in the PBPK model resulted in underprediction of propofol clearance regardless of the source of in vitro data; the predicted value did not exceed 35% of the observed clearance. Subsequently, propofol clinical data from three dose levels in intact patients and anhepatic subjects were used for the optimization of hepatic and renal CLint in a simultaneous fitting routine. Optimization process highlighted that renal glucuronidation clearance was underpredicted to a greater extent than liver clearance, requiring empirical scaling factors of 17 and 9, respectively. The use of optimized clearance parameters predicted hepatic and renal extraction ratios within 20% of the observed values, reported in an additional independent clinical study. This study highlights the complexity involved in assessing the contribution of extrahepatic clearance mechanisms and illustrates the application of PBPK modeling, in conjunction with clinical data, to assess prediction of clearance from in vitro data for each tissue individually. PMID:23303442

Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

PubMed

Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2016-08-01

Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Organochlorine-induced histopathology in kidney and liver tissue from Arctic fox (Vulpes lagopus).

PubMed

Sonne, Christian; Wolkers, Hans; Leifsson, Pall S; Jenssen, Bjørn Munro; Fuglei, Eva; Ahlstrøm, Oystein; Dietz, Rune; Kirkegaard, Maja; Muir, Derek C G; Jørgensen, Even

2008-04-01

The effects of persistent organic pollutants on renal and liver morphology in farmed arctic fox (Vulpes lagopus) were studied under experimental conditions. Control animals received a diet containing pork (Sus scrofa) fat with low amounts of persistent organic pollutants, while the diet of the exposed animals contained whale blubber, 'naturally' contaminated with persistent organic pollutants. Polychlorinated biphenyls (PCB) and organochlorine pesticide (OCP) concentrations in the whale blubber were 488 and 395 ng/g wet weight, respectively. Animals were sacrificed and sampled when they were at their fattest (winter) as well as their lowest body weight (summer). The results show that PCB and OCP exposure causes renal (and probably also liver) lesions in arctic foxes. The prevalence of glomerular, tubular and interstitial lesions was significantly highest in the exposed group (chi-square: all p<0.05). The frequency of liver lesions (steatosis, intravascular granulocyte accumulations, interstitial cell infiltrations, lipid granulomas, portal fibrosis and bile duct hyperplasia) were also highest in the exposed group, although not significantly (chi-square: all p>0.05). The prevalence of lesions was not significantly different between lean (winter) and fat (summer) foxes for any of the lesions (chi-square: all p>0.05). We suggest that wild arctic foxes exposed to an environmental cocktail of persistent organic pollutants, such as PCBs and OCPs, in their natural diet are at risk for developing chronic kidney and liver damage. Whether such lesions may have an impact on age and health of the animals remains uncertain.

Dietary oxidized tyrosine (O-Tyr) stimulates TGF-β1-induced extracellular matrix production via the JNK/p38 signaling pathway in rat kidneys.

PubMed

Li, Zhuqing Leslie; Shi, Yonghui; Ding, Yinyi; Ran, Yumei; Le, Guowei

2017-02-01

Oxidized tyrosine (O-Tyr) products have been detected in commercial food and have been demonstrated to induce liver injury in our previous study, but the precise mechanisms of the impact induced by dietary O-Tyr are still unclear. Kidney plays an important role in the metabolism of protein. Accumulation of O-Tyr products, especially the dityrosine (Dityr) and advanced oxidation protein products (AOPPs), in vivo was shown to be associated with many kidney diseases. Therefore, this study determined whether chronic exposure to dietary O-Tyr impaired renal function in rats. After O-Tyr treatment for 24 weeks, rats exhibited oxidative stress and protein oxidation in the kidneys, accompanied with inflammatory reaction and renal dysfunction. Elevated extracellular matrix (ECM) contents and the histological examination (HE and Masson stain) results indicated renal fibrosis. The Real-time PCR and Western blotting assay showed that O-Tyr activated phosphorylation of JNK/p38 and up-regulated the expression of transforming growth factor-β1 (TGF-β1) and Smad 2/3. These results suggest that dietary O-Tyr could induce oxidative stress, inflammation and renal fibrosis through JNK/p38/TGF-β1 signaling pathway. Dityr (accounting for 22 % of the total O-Tyr material) may be responsible for the O-Tyr-induced injury. This study also provides a modified procedure for separation and purification of Dityr, the main oxidized product in O-Tyr.

Symplocos cochinchinensis attenuates streptozotocin-diabetes induced pathophysiological alterations of liver, kidney, pancreas and eye lens in rats.

PubMed

Antu, Kalathookunnel Antony; Riya, Mariam Philip; Mishra, Arvind; Sharma, Sharad; Srivastava, Arvind K; Raghu, Kozhiparambil Gopalan

2014-09-01

The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) has been explored against hyperglycemia associated secondary complications in streptozotocin induced diabetic rat model. The experimental groups consist of normal control (NC), diabetic control (DC), DC + metformin 100 mg kg(-1) bwd, DC + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers like malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR activity (15.99%), and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug. Copyright © 2014 Elsevier GmbH. All rights reserved.

Prevalence of BK virus replication among recipients of solid organ transplants.

PubMed

Muñoz, Patricia; Fogeda, Marta; Bouza, Emilio; Verde, Eduardo; Palomo, Jesus; Bañares, Rafael

2005-12-15

BK virus (BKV) has been implicated as a cause of nephritis and graft loss in 2%-9% of kidney transplant recipients, but the prevalence among recipients of other solid organ transplants (SOTs) has not been well established. Our objective was to determine the prevalence of BKV infection for all types of SOT recipients at our medical center. A total of 156 consecutive SOT recipients were studied, of whom 49 received kidney transplants, 43 received heart transplants, and 64 received liver transplants. Samples were obtained a median of 559 days (range, 1-9481 days) after transplantation. Nested polymerase chain reaction was performed for detection of BKV DNA in urine and plasma specimens. BKV was found in 19% of urine specimens and 6% of plasma specimens. The prevalence of viruria after kidney, heart, and liver transplantation was 26.5%, 25.5%, and 7.8%, respectively. BKV viremia was detected in 12.2% of kidney transplant recipients and 7% of heart transplant recipients. Mean creatinine levels were higher in patients with BKV viruria or viremia (1.9 and 3.5 mg/dL, respectively) than in patients with no BKV replication (1.3 mg/dL). Independent factors related to impaired renal function were renal transplantation (odds ratio [OR], 14.4); BKV replication, including viruria or viremia (OR, 3.3); and mycophenolate use (OR, 2.6). BKV is common in all types of SOT recipients, particularly those who have received heart or kidney transplants.

[Natural history, diagnosis and treatment of chronic hepatitis B and C in hemodialysis patients].

PubMed

Nicolardi, Erica; Grieco, Antonio; Rapaccini, Gian Ludovico; Pompili, Maurizio

2010-01-01

Chronic hepatitis B and C are important causes of liver disease in hemodialysis units. The most important route of transmission is the inapparent parenteral route; known risk factors are the high prevalence of HBV and HCV infections in hemodialysis units, previous blood transfusions, long-term dialysis treatment, frequent changes of hemodialysis unit, and previous renal transplants. The source, time and duration of infection are often difficult to ascertain. The studies investigating the natural history of viral hepatitis in hemodialysis patients are few and limited by a short follow-up, but they show an independent and negative impact on survival due to an increased risk of liver cirrhosis and hepatocellular carcinoma. The treatment options include conventional or pegylated interferon (alone or in association with ribavirin) and the nucleoside/nucleotide analogs. The aim of treatment is viral eradication or persistent suppression of viral replication. The altered pharmacokinetics, the increased risk of drug-related toxicity, and the need for renal transplant complicate the management of antiviral therapy. In patients with chronic HBV infection and active replication the most common approach is persistent suppression of viral replication using nucleoside/nucleotide analogs. As regards hepatitis C, several clinical trials evaluating conventional interferon monotherapy have shown higher sustained virological response and dropout rates in dialysis patients than in patients with normal kidney function. Data about pegylated interferon as monotherapy or in association with ribavirin are promising but limited. Hemodialyzed patients obtaining a sustained virological response often maintain the response after kidney transplantation.

Computed tomography of the liver and kidneys in glycogen storage disease.

PubMed

Doppman, J L; Cornblath, M; Dwyer, A J; Adams, A J; Girton, M E; Sidbury, J

1982-02-01

Glycogen, in concentrations encountered in von Gierke's disease, has computed tomography (CT) attenuation coefficients in the 50 to 70 Hounsfield unit (HU: 1,000 scale) range and accounts for the increased density of the liver. However, in eight patients with Type I glycogen storage disease, simultaneous hepatic infiltration with fat and glycogen led to a range of liver CT densities from 13 to 80 HU. Fatty infiltration may facilitate the demonstration of hepatic tumors in older patients with this disease. Half the patients showed increased attenuation coefficients of the renal cortex, indicating glycogen deposition in the kidneys.

Oral ulcers produced by mycophenolate mofetil in two liver transplant patients.

PubMed

Naranjo, J; Poniachik, J; Cisco, D; Contreras, J; Oksenberg, D; Valera, J M; Díaz, J C; Rojas, J; Cardemil, G; Mena, S; Castillo, J; Rencoret, G; Godoy, J; Escobar, J; Rodríguez, J; Leyton, P; Fica, A; Toledo, C

2007-04-01

Oral ulcers are a frequent problem in transplant medicine. It is important to consider infectious etiologies, exacerbated by the immunosuppressive treatment, but other etiologies are also possible, like adverse drug reactions. Mycophenolate mofetil (MMF) is an immunosuppressive medication that has been used in combination with calcineurin inhibitors and steroids. Reports of renal transplant patients with oral ulcers related to MMF have appeared lately and herein we have described 2 cases in liver transplant patients. Their oral ulcers resolved quickly after suspension of the medication. Our 2 cases in liver transplant patients represented a unique setting for this type of complication.

Cyclosporin A treatment induces overexpression of P-glycoprotein in the kidney and other tissues.

PubMed

Jetté, L; Beaulieu, E; Leclerc, J M; Béliveau, R

1996-05-01

To see whether P-glycoprotein (PGP) expressed in renal brush-border membranes (BBM) could interact with compounds known as modulators of multidrug resistance (MDR), photoaffinity-labeling experiments were performed. A 145k-Da protein was photolabeled with [125I] iodoarylazidoprazosin, and this labeling was reduced in the presence of cyclosporin A (CsA) and PSC-833 (PSC). Interaction of CsA with PGP was further investigated by treating rats with daily subcutaneous injections of CsA (10 mg.kg-1.day-1). After this treatment, PGP expression levels were dramatically increased in renal BBM, intestine, liver, and many other tissues except the brain. This induction was a reversible process, since after cessation of CsA administration PGP levels declined to reach values similar to those of the control groups. The increase in PGP expression in the kidney was also detected in photolabeling experiments, suggesting the induction of a functional PGP. A higher dose of CsA (50 mg/kg) given as a bolus injection did not modify PGP expression] in renal BBM. These results demonstrate that CsA induces reversible overexpression of PGP in the rat. This may present significant relevance in the design of clinical trials using CsA as a chemosensitizing agent.

Presence of transient hydronephrosis immediately after surgery has a limited influence on renal function 1 year after ileal neobladder construction.

PubMed

Narita, Takuma; Hatakeyama, Shingo; Koie, Takuya; Hosogoe, Shogo; Matsumoto, Teppei; Soma, Osamu; Yamamoto, Hayato; Yoneyama, Tohru; Tobisawa, Yuki; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

2017-08-31

Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction. Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery. There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition. The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction.

Invasive liver abscess syndrome caused by Klebsiella pneumoniae with definite K2 serotyping in Japan: a case report.

PubMed

Seo, Ryota; Kudo, Daisuke; Gu, Yoshiaki; Yano, Hisakazu; Aoyagi, Tetsuji; Omura, Taku; Irino, Shigemi; Kaku, Mitsuo; Kushimoto, Shigeki

2016-12-01

Klebsiella pneumonia is a well-known human pathogen, and recently, a distinct invasive syndrome caused by K. pneumoniae serotypes K1 and K2 has been recognized in Southeast Asia. This syndrome is characterized by primary liver abscess and extrahepatic complications resulting from bacteremic dissemination. We report the first adult case of primary liver abscess caused by the definite K2 serotyped pathogen, with endogenous endophthalmitis in Japan. A 64-year-old woman was admitted to a nearby hospital for a high fever and diarrhea. She had visual loss of her right eye, renal dysfunction, and thrombocytopenia within 24 h from admission. She was transferred to our institution. On admission, she had no alteration of mental status and normal vital signs; however, she had almost complete ablepsia of the right eye. Laboratory data showed severe inflammation, liver dysfunction, thrombocytopenia, an increased serum creatinine level, and coagulopathy. Computed tomography showed a low density area in the right lobe of the liver. Invasive liver abscess syndrome probably caused by K. pneumonia was highly suspected and immediately administered broad-spectrum antibiotics for severe sepsis. Concurrently, endogenous endophthalmitis was diagnosed, and we performed vitrectomy on the day of admission. The blood culture showed K. pneumoniae infection. Percutaneous drainage of the liver abscess was also performed. Although she was discharged in a good general condition on day 22, she had complete ablepsia of the right eye. The K2A gene was detected by polymerase chain reaction (PCR), which is consistent with the K2 serotype. PCR was also positive for the virulence-associated gene rmpA. Final diagnosis was invasive liver abscess syndrome caused by K2 serotype K. pneumonia. Although the primary liver abscess caused by K. pneumoniae with a hypermucoviscous phenotype is infrequently reported outside Southeast Asia, physicians should recognize this syndrome, and appropriate diagnosis and treatment is essential for saving patients' lives and preserving organ function, especially for visual acuity.

[Two-stage hepatectomy for hepatic metastasis and supra renal vena cava reconstruction].

PubMed

Nicoluzzi, João Eduardo

2012-12-01

Two-stage hepatectomy uses compensatory liver regeneration after a first noncurative hepatectomy to enable a second curative resection. Herein we report the tecnical aspects of the management of a thirty-seven years-old woman with colorectal metastasis to the liver eligible because single resection could not achieve complete treatment, even in combination with chemotherapy, portal embolization, or radiofrequency, but tumors could be totally removed by two sequential resections.

Acute Liver Failure During Deferasirox Chelation: A Toxicity Worth Considering.

PubMed

Menaker, Nathan; Halligan, Katharine; Shur, Natasha; Paige, John; Hickling, Matthew; Nepo, Anne; Weintraub, Lauren

2017-04-01

This case report details a unique case of acute, reversible liver failure in a 12-year-old male with sickle cell anemia on chronic transfusion protocol and deferasirox chelation. There is substantial literature documenting deferasirox-induced renal injury, including Fanconi syndrome, but less documentation of hepatic toxicity and few reports of hepatic failure. The case highlights the importance of close monitoring of ferritin, bilirubin, and transaminases for patients on deferasirox.

21 CFR 700.18 - Use of chloroform as an ingredient in cosmetic products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... animals. Studies conducted by the National Cancer Institute have demonstrated that the oral administration of chloroform to mice and rats induced hepatocellular carcinomas (liver cancer) in mice and renal...

21 CFR 700.18 - Use of chloroform as an ingredient in cosmetic products.

Code of Federal Regulations, 2011 CFR

2011-04-01

... animals. Studies conducted by the National Cancer Institute have demonstrated that the oral administration of chloroform to mice and rats induced hepatocellular carcinomas (liver cancer) in mice and renal...

21 CFR 700.18 - Use of chloroform as an ingredient in cosmetic products.

Code of Federal Regulations, 2013 CFR

2013-04-01

... animals. Studies conducted by the National Cancer Institute have demonstrated that the oral administration of chloroform to mice and rats induced hepatocellular carcinomas (liver cancer) in mice and renal...

21 CFR 700.18 - Use of chloroform as an ingredient in cosmetic products.

Code of Federal Regulations, 2012 CFR

2012-04-01

... animals. Studies conducted by the National Cancer Institute have demonstrated that the oral administration of chloroform to mice and rats induced hepatocellular carcinomas (liver cancer) in mice and renal...

21 CFR 700.18 - Use of chloroform as an ingredient in cosmetic products.

Code of Federal Regulations, 2014 CFR

2014-04-01

... animals. Studies conducted by the National Cancer Institute have demonstrated that the oral administration of chloroform to mice and rats induced hepatocellular carcinomas (liver cancer) in mice and renal...

A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.

PubMed

Vichinsky, Elliott; Onyekwere, Onyinye; Porter, John; Swerdlow, Paul; Eckman, James; Lane, Peter; Files, Beatrice; Hassell, Kathryn; Kelly, Patrick; Wilson, Felicia; Bernaudin, Françoise; Forni, Gian Luca; Okpala, Iheanyi; Ressayre-Djaffer, Catherine; Alberti, Daniele; Holland, Jaymes; Marks, Peter; Fung, Ellen; Fischer, Roland; Mueller, Brigitta U; Coates, Thomas

2007-02-01

Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.

Postpartum plasma exchange in a woman with suspected thrombotic thrombocytopenic purpura (TTP) vs. hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP): a case study.

PubMed

Myers, Linda

2010-01-01

The occurrence of a hypercoagulable state and decreasing concentration of ADAMTS 13 in late pregnancy and during the postpartum period increases the risk for a woman to develop life-threatening thrombotic thrombocytopenic purpura (TTP). This is also the time of great risk for the more common obstetric complications of preeclampsia; eclampsia; and hemolysis, elevated liver functions tests, low platelets (HELLP) syndrome. These conditions are associated with high maternal and perinatal mortality. Differential diagnosis may be difficult due to the overlapping of clinical and laboratory findings, including thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, and renal insufficiency, making it difficult or impossible to distinguish them from TTP. Management of microangiopathic disorders encountered during pregnancy differ; therefore, an accurate diagnosis is required. Outcomes of TTP without plasma exchange therapy (TPE) are almost uniformly fatal. Early recognition and management of symptoms with prompt and aggressive TPE is essential when TTP is suspected.

Biology of portal hypertension.

PubMed

McConnell, Matthew; Iwakiri, Yasuko

2018-02-01

Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.

Class III obesity is a risk factor for the development of acute-on-chronic liver failure in patients with decompensated cirrhosis.

PubMed

Sundaram, Vinay; Jalan, Rajiv; Ahn, Joseph C; Charlton, Michael R; Goldberg, David S; Karvellas, Constantine J; Noureddin, Mazen; Wong, Robert J

2018-04-28

Acute-on-chronic liver failure (ACLF) is a syndrome of systemic inflammation and organ failures. Obesity, also characterized by chronic inflammation, is a risk factor among patients with cirrhosis for decompensation, infection, and mortality. Our aim was to test the hypothesis that obesity predisposes patients with decompensated cirrhosis to the development of ACLF. We examined the United Network for Organ Sharing (UNOS) database, from 2005-2016, characterizing patients at wait-listing as non-obese (body mass index [BMI] <30), obese class I-II (BMI 30-39.9) and obese class III (BMI ≥40). ACLF was determined based on the CANONIC study definition. We used Cox proportional hazards regression to assess the association between obesity and ACLF development at liver transplantation (LT). We confirmed our findings using the Nationwide Inpatient Sample (NIS), years 2009-2013, using validated diagnostic coding algorithms to identify obesity, hepatic decompensation and ACLF. Logistic regression evaluated the association between obesity and ACLF occurrence. Among 387,884 patient records with decompensated cirrhosis, 116,704 (30.1%) were identified as having ACLF in both databases. Multivariable modeling from the UNOS database revealed class III obesity to be an independent risk factor for ACLF at LT (hazard ratio 1.24; 95% CI 1.09-1.41; p <0.001). This finding was confirmed using the NIS (odds ratio 1.30; 95% CI 1.25-1.35; p <0.001). Regarding specific organ failures, analysis of both registries demonstrated patients with class I-II and class III obesity had a greater prevalence of renal failure. Class III obesity is a newly identified risk factor for ACLF development in patients with decompensated cirrhosis. Obese patients have a particularly high prevalence of renal failure as a component of ACLF. These findings have important implications regarding stratifying risk and preventing the occurrence of ACLF. In this study, we identify that among patients with decompensated cirrhosis, class III obesity (severe/morbid obesity) is a modifiable risk factor for the development of acute-on-chronic liver failure (ACLF). We further demonstrate that regarding the specific organ failures associated with ACLF, renal failure is significantly more prevalent in obese patients, particularly those with class III obesity. These findings underscore the importance of weight management in cirrhosis, to reduce the risk of ACLF. Patients with class III obesity should be monitored closely for the development of renal failure. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury

PubMed Central

Siow, Yaw L.; Isaak, Cara K.

2016-01-01

Ischemia-reperfusion is a common cause for acute kidney injury and can lead to distant organ dysfunction. Glutathione is a major endogenous antioxidant and its depletion directly correlates to ischemia-reperfusion injury. The liver has high capacity for producing glutathione and is a key organ in modulating local and systemic redox balance. In the present study, we investigated the mechanism by which kidney ischemia-reperfusion led to glutathione depletion and oxidative stress. The left kidney of Sprague-Dawley rats was subjected to 45 min ischemia followed by 6 h reperfusion. Ischemia-reperfusion impaired kidney and liver function. This was accompanied by a decrease in glutathione levels in the liver and plasma and increased hepatic lipid peroxidation and plasma homocysteine levels. Ischemia-reperfusion caused a significant decrease in mRNA and protein levels of hepatic glutamate-cysteine ligase mediated through the inhibition of transcription factor Nrf2. Ischemia-reperfusion inhibited hepatic expression of cystathionine γ-lyase, an enzyme responsible for producing cysteine (an essential precursor for glutathione synthesis) through the transsulfuration pathway. These results suggest that inhibition of glutamate-cysteine ligase expression and downregulation of the transsulfuration pathway lead to reduced hepatic glutathione biosynthesis and elevation of plasma homocysteine levels, which, in turn, may contribute to oxidative stress and distant organ injury during renal ischemia-reperfusion. PMID:27872680

Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia

PubMed Central

Fukui, Hiroshi

2015-01-01

A “leaky gut” may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. PMID:25848468

Effects of lornoxicam and intravenous ibuprofen on erythrocyte deformability and hepatic and renal blood flow in rats.

PubMed

Arpacı, Hande; Çomu, Faruk Metin; Küçük, Ayşegül; Kösem, Bahadır; Kartal, Seyfi; Şıvgın, Volkan; Turgut, Hüseyin Cihad; Aydın, Muhammed Enes; Koç, Derya Sebile; Arslan, Mustafa

2016-01-01

Change in blood supply is held responsible for anesthesia-related abnormal tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may be detected after surgery performed under general anesthesia. It was shown that nonsteroidal anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or intravenous (iv) ibuprofen are commonly preferred analgesic agents for postoperative pain management. In this study, we aimed to investigate the effects of lornoxicam (2 mg/kg, iv) and ibuprofen (30 mg/kg, iv) on erythrocyte deformability, as well as hepatic and renal blood flows, in male rats. Eighteen male Wistar albino rats were randomly divided into three groups as follows: iv lornoxicam-treated group (Group L), iv ibuprofen-treated group (Group İ), and control group (Group C). Drug administration was carried out by the iv route in all groups except Group C. Hepatic and renal blood flows were studied by laser Doppler, and euthanasia was performed via intra-abdominal blood uptake. Erythrocyte deformability was measured using a constant-flow filtrometry system. Lornoxicam and ibuprofen increased the relative resistance, which is an indicator of erythrocyte deformability, of rats (P=0.016). Comparison of the results from Group L and Group I revealed no statistically significant differences (P=0.694), although the erythrocyte deformability levels in Group L and Group I were statistically higher than the results observed in Group C (P=0.018 and P=0.008, respectively). Hepatic and renal blood flows were significantly lower than the same in Group C. We believe that lornoxicam and ibuprofen may lead to functional disorders related to renal and liver tissue perfusion secondary to both decreased blood flow and erythrocyte deformability. Further studies regarding these issues are thought to be essential.

Current management of autosomal dominant polycystic kidney disease.

PubMed

Akoh, Jacob A

2015-09-06

Autosomal dominant polycystic kidney disease (ADPKD), the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging (MRI) were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the financial impact on society of the disease. Current treatment strategies include reducing: cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials (RCT) including mammalian target of rapamycin inhibitors, somatostatin analogues and a vasopressin V2 receptor antagonist have been performed to study the effect of diverse drugs on growth of renal and hepatic cysts, and on deterioration of renal function. Prophylactic native nephrectomy is indicated in patients with a history of cyst infection or recurrent haemorrhage or to those in whom space must be made to implant the graft. The absence of large RCT on various aspects of the disease and its treatment leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease (ESRD). The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a first step towards trying newer interventions so as to develop updated clinical management guidelines.

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction.

PubMed

Hamamura, Kengo; Matsunaga, Naoya; Ikeda, Eriko; Kondo, Hideaki; Ikeyama, Hisako; Tokushige, Kazutaka; Itcho, Kazufumi; Furuichi, Yoko; Yoshida, Yuya; Matsuda, Masaki; Yasuda, Kaori; Doi, Atsushi; Yokota, Yoshifumi; Amamoto, Toshiaki; Aramaki, Hironori; Irino, Yasuhiro; Koyanagi, Satoru; Ohdo, Shigehiro

2016-03-04

Chronic kidney disease (CKD) is associated with an increase in serum retinol; however, the underlying mechanisms of this disorder are poorly characterized. Here, we found that the alteration of hepatic metabolism induced the accumulation of serum retinol in 5/6 nephrectomy (5/6Nx) mice. The liver is the major organ responsible for retinol metabolism; accordingly, microarray analysis revealed that the hepatic expression of most CYP genes was changed in 5/6Nx mice. In addition, D-box-binding protein (DBP), which controls the expression of several CYP genes, was significantly decreased in these mice. Cyp3a11 and Cyp26a1, encoding key proteins in retinol metabolism, showed the greatest decrease in expression in 5/6Nx mice, a process mediated by the decreased expression of DBP. Furthermore, an increase of plasma transforming growth factor-β1 (TGF-β1) in 5/6Nx mice led to the decreased expression of the Dbp gene. Consistent with these findings, the alterations of retinol metabolism and renal dysfunction in 5/6Nx mice were ameliorated by administration of an anti-TGF-β1 antibody. We also show that the accumulation of serum retinol induced renal apoptosis in 5/6Nx mice fed a normal diet, whereas renal dysfunction was reduced in mice fed a retinol-free diet. These findings indicate that constitutive Dbp expression plays an important role in mediating hepatic dysfunction under CKD. Thus, the aggravation of renal dysfunction in patients with CKD might be prevented by a recovery of hepatic function, potentially through therapies targeting DBP and retinol. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Human Sodium Phosphate Transporter 4 (hNPT4/SLC17A3) as a Common Renal Secretory Pathway for Drugs and Urate*

PubMed Central

Jutabha, Promsuk; Anzai, Naohiko; Kitamura, Kenichiro; Taniguchi, Atsuo; Kaneko, Shuji; Yan, Kunimasa; Yamada, Hideomi; Shimada, Hidetaka; Kimura, Toru; Katada, Tomohisa; Fukutomi, Toshiyuki; Tomita, Kimio; Urano, Wako; Yamanaka, Hisashi; Seki, George; Fujita, Toshiro; Moriyama, Yoshinori; Yamada, Akira; Uchida, Shunya; Wempe, Michael F.; Endou, Hitoshi; Sakurai, Hiroyuki

2010-01-01

The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases. Human serum urate levels are largely determined by urate reabsorption and secretion in the kidney. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for renal urate secretion remain unknown. In this report, we demonstrate that an orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a multispecific organic anion efflux transporter expressed in the kidneys and liver. hNPT4 was localized at the apical side of renal tubules and functioned as a voltage-driven urate transporter. Furthermore, loop diuretics, such as furosemide and bumetanide, substantially interacted with hNPT4. Thus, this protein is likely to act as a common secretion route for both drugs and may play an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4 was suggested by two hyperuricemia patients with missense mutations in SLC17A3. These mutated versions of hNPT4 exhibited reduced urate efflux when they were expressed in Xenopus oocytes. Our findings will complete a model of urate secretion in the renal tubular cell, where intracellular urate taken up via OAT1 and/or OAT3 from the blood exits from the cell into the lumen via hNPT4. PMID:20810651

Clinical course of dengue fever and its impact on renal function in renal transplant recipients and patients with chronic kidney disease.

PubMed

Arun Thomas, E T; George, Jacob; Sruthi, Devi; Vineetha, N S; Gracious, Noble

2018-04-01

Dengue fever is a mosquito-borne viral disease endemic in many tropical and sub-tropical countries. There is only limited data in the literature about dengue fever in renal transplant recipients and patients with chronic kidney disease. This study compares the clinical course of dengue fever and its impact on renal function in renal transplant recipients, patients with chronic kidney disease and patients with normal base line renal function. An observational study was conducted from 1 st May to 31 st July 2017, at a tertiary care centre of South India. A major epidemic of dengue had occurred during the study period. Twelve renal transplant recipients, 22 patients with CKD and 58 patients with normal baseline renal function (control group) admitted with dengue fever were prospectively studied. Nadir WBC count was lowest in renal transplant recipients (2575 + 1187/mm 3 ), [P<0.001]. Renal transplant recipients took more time for normalisation of platelet count (6 + 4.5 days), [P<0.001]. All 22 patients with CKD and 11 of 12 renal transplant recipients had worsening of renal function where as only 17 of 58 patients in the control group had worsening [P<0.001]. Sixteen patients with CKD, one renal transplant recipient and none among control group required hemodialysis [P<0.001]. Dialysis requiring patients had more hemoconcentration (52.5+ 19.9% increase in haemoglobin), [P<0.001]. Seven patients with CKD were dialysis dependent at the end of 2 weeks. Clinical features of dengue fever were different in renal transplant recipients and patients with CKD. Severe worsening of renal function was common in CKD patients. Worsening of renal function in renal transplant recipients was less severe and transient. This article is protected by copyright. All rights reserved.

Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

PubMed Central

2010-01-01

Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and efficient, especially when the studied parameters are used in combination. The potential implication of this study is to provide a non-invasive method that allows follow-up studies of fatty liver disease and cirrhosis of individual rats for pre-clinical drug or cell based therapies. PMID:20113491

Transjugular Renal Biopsy: Our Experience and Technical Considerations

DOE Office of Scientific and Technical Information (OSTI.GOV)

See, Teik Choon, E-mail: teikchoon.see@addenbrookes.nhs.u; Thompson, Barbara C.; Howie, Alexander J.

2008-09-15

The purpose of this study was to describe the indications for and technique of transjugular renal biopsy (TJRB) and evaluate the efficacy and complications of this method. We performed a retrospective review of 59 patients who underwent TJRB using the Quick-core needle biopsy system (Cook, Letchworth, UK) over a 4-year period. The indications for obtaining renal biopsy included acute renal failure, chronic renal failure, nephrotic syndrome, and proteinuria with or without other associated disease. Indications for the transjugular approach included coagulopathy, biopsy of a solitary kidney or essentially single functioning kidney, simultaneous renal and hepatic biopsy, morbid obesity, and failedmore » percutaneous biopsy. All but four cases were performed via the right internal jugular vein. The right, left, or both renal veins were cannulated in 41, 14, and 4 cases, respectively. Combined liver and renal biopsies were obtained in seven cases. Diagnostic biopsy specimens were obtained in 56 of 59 patients (95%). The number and size of tissue cores ranged from 1 to 9 mm and from 1 to 20 mm, respectively. The mean numbers of glomeruli per procedure on light microscopy and electron microscopy were 10.3 and 2.6, respectively. Specimens for immunohistology were acquired in 49 cases, of which 40 were adequate. Of the 56 successful TJRB procedures, 34 (61%) were associated with isolated capsular perforation (19), contained subcapsular leak (10), isolated collecting system puncture (1), and concurrent collecting system and capsular perforation (4). There was a significant increase in capsular perforation with six or more needle passes, although no significant correlation was seen between number of needle passes and complication. Six patients had minor complications defined as hematuria or loin pain. Seven patients developed major complications, of whom five received blood transfusion alone. Two required intervention: in one an arteriocalyceal fistula was embolized and the patient was temporarily dialyzed; the remaining patient required ureteric stenting. In conclusion, TJRB provides an adequate yield for diagnosis. Complication rates are relatively high, but patients are also at high risk from the conventional percutaneous approach. Patient selection and optimization are critical to avoid major complications.« less

Morphological changes in the liver and kidneys of rats subjected to terminal ileum exclusion during obstructive cholestasis.

PubMed

Costa, Evandro Luis de Oliveira; Azevedo, Geraldo Magela de; Petroianu, Andy

2014-06-01

To investigate the effects of ileal exclusion on hepatic and renal morphology in extra-hepatic cholestasis. Twenty four rats were distributed into three groups. Group 1 (control) underwent laparotomy and laparorrhaphy. The animals in groups 2 and 3 underwent hepatic duct ligature and kept in cholestasis for four weeks. After this period, the rats in groups 2 and 3 underwent internal biliary derivation. In Group 3, the last ten centimeters of the terminal ileum were by passed and excluded. Four weeks later, histological and biochemical analysis were performed in all animals of the three groups. In Group 1, no abnormalities regarding hepatic morphology were observed. All animals from groups 2 and 3 presented hepatic fibrosis. No difference was observed between the two groups. No morphological differences in renal histology could be identified among the three groups. There were differences in AST (p<0.05), ALT (p<0.05), direct bilirubin (p<0.05), ƔGT (p<0.05), urea (p<0.05) and creatinine (p<0.05) in Group 3 compared to control. The distal ileum exclusion had no influence upon the hepatic and renal morphological alterations, and biochemical liver and kidney tests have worsened.

Geometric Alteration of Renal Arteries After Fenestrated Grafting and the Impact on Renal Function.

PubMed

Ou, Jiale; Chan, Yiu-Che; Chan, Crystal Yin-Tung; Cheng, Stephen W K

2017-05-01

This study aims to investigate the degree of geometric change on renal arteries and its impact on renal function after fenestrated endovascular aortic repair (fEVAR). Twenty-five patients with fEVAR were included. There were 47 renal arteries target vessels, and 43 of these (22 left and 21 right vessels) stented successfully. Their preoperative and first postoperative follow-up computed tomography (CT) images were reconstructed using the Aquarius workstation (TeraRecon, San Mateo, CA, USA). The superior mesenteric artery (SMA) or celiac axis (if SMA was stented) was appointed as reference origin. The longitudinal orientation of a renal artery or a stent was represented by a takeoff angle (ToA) between the renal artery or stent and the distal abdominal aorta. The postoperative stent ToAs were compared with those of preoperative renal arteries. Preoperative and short-term postoperative serum creatinine levels were measured. Renal function impairment was indicated as a >30% or >2.0 mg/dL rise in serum creatinine compared to the preoperative level. The relationship between postoperative renal function impairment and the stent orientation or geometric changes in renal arteries was correlated. The patency rate of renal arteries was 100% at the first postoperative CT review. The average ToAs of both renal arteries were significantly enlarged after stenting (P < 0.05). Seven stent deformations (16.3%) in four patients (16.0%) were observed. They were attributed to caudal misalignment of the fenestrated stent graft (n = 6) or inaccurate graft sizing (n = 1). There was no stent fracture or target vessel loss. Postoperatively, nine patients (36.0%) at day 1 and 10 patients (41.7%) after 3 months suffered the renal function impairment. This was found not to be associated with the stent angulation or angular change of the renal arteries (both P > 0.05). The three patients with stent deformation due to misalignment suffered postoperative renal function impairment and continuing deterioration in renal function. Implanted renal stents could angulate renal arteries more cephalad after fenestrated stenting. Postoperative renal function impairment was not associated with the stent orientation and changes in vessel orientation. Accurate fenestrated alignment is important to maintain stent performance and preserve renal function. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical and toxicological evaluation of methanol extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed on hematological parameters and hepatorenal functions in mice.

PubMed

Mazumder, Upal Kanti; Gupta, Malaya; Pal, Dilipkumar; Bhattacharya, Shiladitya

2003-01-01

Methanol extract of Cuscuta reflexa Roxb. stem (MECR) contain flavonoids (0.2%) and Corchorus olitorius Linn. seed (MECO) was found to contain steroids and cardenolide glycosides. Effects of multiple weekly dose of MECR (25, 50, 75 mg/kg, i.p.) and MECO (15, 20, 25 mg/kg, i.p.) on liver and kidney functions and hematological parameters in mice were studied. No significant alteration of RBC count and hemoglobin content was observed in all dose level of treatment in MECR and MECO treated mice whereas significant increase of clotting time was seen in moderate and high doses in both case. MECR and MECO both caused significant increase in WBC count only in high dose level of treatment. Both the extracts in medium and high dose level increased SGOT, SGPT, NPN and plasma cholesterol significantly. Serum alkaline phosphatase and total bilirubin were also increased by both moderate and high dose level of treatments in MECR and MECO treated mice respectively. Low dose of both the extract did not exhibit any significant change of creatinine and serum protein level. But high dose level of MECR and MECO significantly increased creatinine level. Increase in plasma cholesterol may be due to decrease in cholesterol catabolism owing to liver dysfunction of due to the intake of MECO itself as it was found to be steroid in nature. Elevated level of SGOT, SGPT and serum alkaline phosphatase activity in moderate and high dose level of weekly treated mice may be due to improper liver function following the treatment. Increased urea, non protein nitrogen and creatinine content in blood have been observed with impaired renal function. The slightly higher toxicity in case of MECO treated mice may be due to the presence of cardenolide glycosides in the ME of C. olitorius seed. However, low doses of MECR and MECO (25 and 15 mg/kg, i.p. respectively) did not exhibit any remarkable change on liver and kidney functions and hematological parameters.

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

PubMed Central

Tullos, Nathan; Stewart, Nicholas J.; Surles, Bret

2015-01-01

Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. PMID:25377076

Predictive abilities of cardiovascular biomarkers to rapid decline of renal function in Chinese community-dwelling population: a 5-year prospective analysis.

PubMed

Fu, Shihui; Liu, Chunling; Luo, Leiming; Ye, Ping

2017-11-09

Predictive abilities of cardiovascular biomarkers to renal function decline are more significant in Chinese community-dwelling population without glomerular filtration rate (GFR) below 60 ml/min/1.73m 2 , and long-term prospective study is an optimal choice to explore this problem. Aim of this analysis was to observe this problem during the follow-up of 5 years. In a large medical check-up program in Beijing, there were 948 participants with renal function evaluated at baseline and follow-up of 5 years. Physical examinations were performed by well-trained physicians. Blood samples were analyzed by qualified technicians in central laboratory. Median rate of renal function decline was 1.46 (0.42-2.91) mL/min/1.73m 2 /year. Rapid decline of renal function had a prevalence of 23.5% (223 participants). Multivariate linear and Logistic regression analyses confirmed that age, sex, baseline GFR, homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP) had independently predictive abilities to renal function decline rate and rapid decline of renal function (p < 0.05 for all). High-sensitivity cardiac troponin T (hs-cTnT), carotid femoral pulse wave velocity and central augmentation index had no statistically independent association with renal function decline rate and rapid decline of renal function (p > 0.05 for all). Homocysteine and NT-proBNP rather than hs-cTnT had independently predictive abilities to rapid decline of renal function in Chinese community-dwelling population without GFR below 60 ml/min/1.73m 2 . Baseline GFR was an independent factor predicting the rapid decline of renal function. Arterial stiffness and compliance had no independent effect on rapid decline of renal function. This analysis has a significant implication for public health, and changing the homocysteine and NT-proBNP levels might slow the rapid decline of renal function.

The additive effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 function in diabetic rats.

PubMed

Thongnak, Laongdao; Pongchaidecha, Anchalee; Jaikumkao, Krit; Chatsudthipong, Varanuj; Chattipakorn, Nipon; Lungkaphin, Anusorn

2017-10-19

Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several "pleiotropic" effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.

Effects of continuous and pulsatile flows generated by ventricular assist devices on renal function and pathology.

PubMed

Miyamoto, Takuma; Karimov, Jamshid H; Fukamachi, Kiyotaka

2018-03-01

Continuous-flow (CF) left ventricular assist devices (LVADs) are widely used to treat end-stage heart failure. Despite substantial improvement in clinical results, numerous complications remain associated with this technology. Worsening renal function is one, associated with morbidity and mortality in patients supported by CF LVADs. The effects of CF LVAD support on renal function have been investigated since the mid-1990s by many research groups. Area covered: We review the current status of LVAD therapy, experimental results regarding the effects of types of flow generated by LVADs on renal function and pathology, changes in renal function after LVAD implant, the influence of renal function on outcomes, and risk factors for renal dysfunction post implant. This information was obtained through online databases and direct extraction of single studies. Expert commentary: Immediately after CF LVAD implantation, renal function improves temporarily as patients recover from the kidneys' previously low perfusion and congestive state. However, many studies have shown that this initially recovered renal function gradually declines during long-term CF LVAD support. Although it is known that CF LVAD support adversely affects renal function over the long term, just how it does has not yet been clearly defined in terms of clinical symptoms or signs.

Preservation of nutritional-status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis.

PubMed

Sorrentino, Paolo; Castaldo, Giuseppe; Tarantino, Luciano; Bracigliano, Alessandra; Perrella, Alessandro; Perrella, Oreste; Fiorentino, Francesco; Vecchione, Raffaela; D' Angelo, Salvatore

2012-04-01

Refractory ascites in liver-cirrhosis is associated with a poor prognosis. We performed a prospective study to investigate whether aggressive nutritional-support could improve outcomes in cirrhotic patients. Cirrhotic patients undergoing serial large-volume paracentesis for refractory-ascites were enrolled and randomized into three groups. Group A received post-paracentesis intravenous nutritional-support in addition to a balanced oral diet and a late-evening protein snack, group B received the same oral nutritional-protocol as the first group but without parenteral support, and group C (the control group) received a low-sodium or sodium-free diet. Clinical, anthropometric and laboratory nutritional parameters and biochemical tests of liver and renal function were reported for 12 months of follow-up. We enrolled 120 patients, who were randomized into three groups of equal size. Patients on the nutritional-protocol showed better preservation of clinical, anthropometric and laboratory nutritional parameters that were associated with decreased deterioration of liver function compared with patients on the low-sodium or sodium-free diet (group C). Groups A and B had lower morbidity and mortality rates than the control group (C). Mortality rates were significantly better in patients who were treated with parenteral-nutritional-support than for the other two groups. In patients who were on the nutritional-protocol, there was a reduction in the requirement of taps for the treatment of refractory ascites. Post-paracentesis parenteral-nutritional-support with a balanced oral diet and an evening protein snack appears to be the best care protocol for patients with liver-cirrhosis that has been complicated by refractory-ascites. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Ultrasound-guided interventional PDT of liver cancer

NASA Astrophysics Data System (ADS)

Zeng, Chaoying; Yang, Dong; Huang, Ping; Zhang, Huijuan; Huang, Muyin; Chen, Ji; Lu, Guorong

1996-09-01

Thirty patients with advanced liver cancer were treated by interstitial photodynamic therapy (PDT). These included 28 hepatocellular carcinoma and two adenocarcinoma, 19 primary tumors and 11 recurred follow other treatments. The diameter of tumors were 7-10cm in 13 cases and 10-16cm in 17 cases. In this study, an argon laser pumped dye laser system was used to give a CW laser beam at 630 nm which was split and coupled into there optical fibers. The patients were injected intravenously with photosensitizer hematoporphyrin derivative at a dose of 5mg/kg body weight 48 hours before PDT. Then the fibers were inserted into tumor by ultrasound- guided percutaneous puncture. The inserted irradiation points were spaced in entire tumor with the light release power 300mW and the irradiation time 12 minutes per point. Total 52 treatments were performed in 30 patients. Among them, 14 cases were treated only one time and 16 cases via 2-3 times. The follow-up was carried out in 25 cases for 12- 24 months. The results show that significant remission was 22 percent in those patients by only one treatment and 62 percent in those via 2 to 3 treatments. The shrink rate of tumor size was over 90 percent in five of six cases after treatment 3. The survival time has been over one year in 12 cases. No obvious change to be found for all patients in liver function test, renal function test and blood routine examination. The level of AFP indicated a descending trend after PDT. This work indicate that PDT is effective and safe for the treatment of large liver cancers including those recurred follow hepatic resection and those failed in hepatic artery infusion embolic chemotherapy.

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure.

PubMed

Gannon, Stephen A; Mukamal, Kenneth J; Chang, James D

2018-06-14

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Molecular-Guided Therapy for Childhood Cancer

ClinicalTrials.gov

2017-07-07

Neuroblastoma; Medulloblastoma; Glioma; Ependymoma; Choroid Plexus Neoplasms; Craniopharyngioma; Dysembryoplastic Neuroepithelial Tumor; Meningioma; Primitive Neuroectodermal Tumors (PNETs); Germ Cell Tumors; Rhabdomyosarcoma; Non-rhabdomyosarcoma; Ewings Sarcoma; Osteosarcoma; Wilms Tumor; Renal Cell Carcinoma; Malignant Rhabdoid Tumor; Clear Cell Sarcoma; Liver Tumors

Schistosomiasis Japonicum Involving the Liver and Colon

DTIC Science & Technology

2007-02-01

contribute to ureteral obstruction, pyelonephritis, and hydronephrosis which can lead to renal failure. Bladder infection has been linked with the...or cystography in particular are very good studies for demonstrating ureteritis cystica, ureteral stricture (or dilation), hydronephrosis , mucosal

21 CFR 862.1475 - Lipoprotein test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases... procedures in subpart E of part 807 of this chapter subject to § 862.9. [52 FR 16122, May 1, 1987, as amended...

Levetiracetam-induced transaminitis in a young male with traumatic brain injury.

PubMed

Rachamallu, Vivekananda; Song, Michael M; Reed, Jace M; Aligeti, Manish

2017-11-01

Levetiracetam is a commonly prescribed antiepileptic drug for seizure prophylaxis in patients with traumatic brain injury (TBI). Levetiracetam metabolism has been reported to be non-dependent on hepatic cytochrome P450 (CYP450) isoenzyme system. Furthermore, levetiracetam and its metabolites are reported to be eliminated from systemic circulation via renal excretion. Therefore, due to its well-known renal clearance mechanism with no dosage adjustments recommended for hepatic impairment, levetiracetam is often chosen as the drug of choice in patients with suspected or ongoing hepatic dysfunction. Furthermore, monitoring of liver enzymes is often not considered to be critical in levetiracetam therapy. However, hepatotoxicity is still possible with levetiracetam. Here, we report on an 18-year-old male with TBI who developed transaminitis with levetiracetam therapy which resolved following the discontinuation of levetiracetam. A close monitoring of liver enzymes and early recognition of hepatotoxicity is still necessary and critical to preventing major sequelae stemming from levetiracetam-induced hepatotoxicity.

Weight loss in a patient with polycystic kidney disease: when liver cysts are no longer innocent bystanders.

PubMed

Cecere, N; Hakem, S; Demoulin, N; Hubert, C; Jabbour, N; Goffette, P; Pirson, Y; Morelle, J

2015-10-01

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disorder, and liver involvement represents one of its major extra-renal manifestations. Although asymptomatic in most patients, polycystic liver disease (PLD) can lead to organ compression, severe disability and even become life-threatening, thereby warranting early recognition and appropriate management. We report the case of a 56-year-old woman with ADPKD and severe weight loss secondary to a giant hepatic cyst compressing the pylorus. Partial hepatectomy was required after failure of cyst aspiration and sclerotherapy, and patient's condition improved rapidly. We discuss the presentation and classification of compressing liver cysts, and the available therapeutic alternatives for this potentially severe complication of ADPKD.

Bardoxolone methyl analogs RTA 405 and dh404 are well tolerated and exhibit efficacy in rodent models of Type 2 diabetes and obesity.

PubMed

Chin, Melanie; Lee, Chun-Yue Ivy; Chuang, Jen-Chieh; Bumeister, Ron; Wigley, W Christian; Sonis, Stephen T; Ward, Keith W; Meyer, Colin

2013-06-15

Bardoxolone methyl and related triterpenoids are well tolerated and efficacious in numerous animal models potentially relevant to patients with Type 2 diabetes and chronic kidney disease. These agents enhance glucose control and regulate lipid accumulation in rodent models of diabetes and obesity, and improve renal function, reduce inflammation, and prevent structural injury in models of renal disease. However, a recent study in Zucker diabetic fatty (ZDF) rats noted poor tolerability with the bardoxolone methyl analog RTA 405 within 1 mo after treatment initiation, although this study was confounded in part by the use of an impure RTA 405 batch. To investigate these discordant observations, the present studies were conducted to further characterize triterpenoids in rodent models of diabetes and obesity. A follow-up study was conducted in ZDF rats with two related triterpenoids (RTA 405 and dh404) for 1.5 mo. Consistent with previous rodent experience, and in contrast to the more recent ZDF report, ZDF rats administered RTA 405 or dh404 exhibited no adverse clinical signs, had laboratory values similar to controls, and exhibited no evidence of adverse liver or kidney histopathology. Additionally, RTA 405 was well tolerated in streptozotocin-induced Type 1 diabetic rats and high-fat-diet-induced obese mice. The present results are consistent with the overall published body of data obtained with triterpenoids and provide further evidence that these molecules are well tolerated without adverse effects on hepatobiliary or renal function in rodent models of diabetes and obesity.

Clinical characteristics of chronic kidney disease of non-traditional causes in women of agricultural communities in El Salvador.

PubMed

Herrera Valdés, Raúl; Orantes, Carlos M; Almaguer López, Miguel; López Marín, Laura; Arévalo, Pedro Alfonso; Smith González, Magaly J; Morales, Fabrizio E; Bacallao, Raymed; Bayarre, Héctor D; Vela Parada, Xavier F

2015-01-01

A chronic kidney disease of non-traditional causes (CKDu) has emerged in Central America and elsewhere, predominantly affecting male farmworkers. In El Salvador (2009), it was the second cause of death in men > 18 years old. Causality has not been determined. Most available research focused on men and there is scarce data on women. Describe the clinical and histopathologic characteristics of CKDu in women of agricultural communities in El Salvador. A descriptive study was carried out in 10 women with CKDu stages 2, 3a, and 3b. Researchers studied demographics, clinical examination; hematological and biochemical analyses, urine sediment, renal injury markers, and assessed renal, cardiac, and peripheral arteries, liver, pancreas, and lung anatomy and functions. Kidney biopsy was performed in all. Data was collected on the Lime Survey platform and exported to SPSS 19.0. Patient distribution by stages: 2 (70%), 3a (10%), 3b (20%). Occupation: agricultural 7; non-agricultural 3. agrochemical exposure 100%; farmworkers 70%; incidental malaria 50%, NSAIDs use 40%; hypertension 40%. nocturia 50%; dysuria 50%; arthralgia 70%; asthenia 50%; cramps 30%, profuse sweating 20%. Renal markers: albumin creatinine ratio (ACR) > 300 mg/g 90%; β microglobulin and neutrophil gelatinase- associated lipocalin (NGAL) presence in 40%. Kidney function: hypermagnesuria 100%; hyperphosphaturia 50%, hypercalciuria 40%; hypernatriuria 30%; hyponatremia 60%, hypocalcemia 50%. Doppler: tibial artery damage 40%. Neurological: reflex abnormalities 30%; Babinski and myoclonus 20%. Neurosensorial hypoacusis 70%. Histopathology: damage restricted mostly to the tubulo-interstitium, urine was essentially bland. CKDu in women is a chronic tubulointerstitial nephropathy with varied extrarenal symptoms.

Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome.

PubMed

Morici, Nuccia; Savonitto, Stefano; Ponticelli, Claudio; Schrieks, Ilse C; Nozza, Anna; Cosentino, Francesco; Stähli, Barbara E; Perrone Filardi, Pasquale; Schwartz, Gregory G; Mellbin, Linda; Lincoff, A Michael; Tardif, Jean-Claude; Grobbee, Diederick E

2017-09-01

Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

A new rat model of auxiliary partial heterotopic liver transplantation with liver dual arterial blood supply.

PubMed

Qiao, Jianliang; Han, Chunlei; Zhang, Junjing; Wang, Zhiyong; Meng, Xingkai

2015-02-01

Auxiliary partial heterotopic liver transplantation (APHLT) with portal vein arterialization is a valuable procedure to be considered in the treatment of patients with acute liver failure and metabolic liver diseases. The aim of this study was to develop a new rat model of APHLT with liver dual arterial blood supply (LDABS). A total of 20 rats were used. The donor liver was resected, and the celiac trunk was reserved. Left and medial hepatic lobes accounting for 70% of the liver mass were removed en bloc and the suprahepatic caval vein was ligated simultaneously. Thus, 30% of the donor liver was obtained as the graft. Sleeve anastomosis of the graft portal vein and splenic artery were performed after narrowing the portal vein lumen through suturing. The right kidney of the recipient was removed, and sleeve anastomosis was performed between the celiac trunk of the graft and the right renal artery of the recipient. In addition, end-to-end anastomosis was performed between the infrahepatic caval vein of the graft and the right renal vein of the recipient. Following the reperfusion of the graft, the blood flow of the arterialized portal vein was controlled within the physiological range through suturing and narrowing under monitoring with an ultrasonic flowmeter. The bile duct of the graft was implanted into the duodenum of the recipient through an internal stent catheter. A 70% section of the native liver (left and medial hepatic lobes) was resected using bloodless hepatectomy. The mean operative duration was 154.5±16.4 min, and the warm and cold ischemia times of the graft were 8.1±1.1 min and 64.5±6.6 min, respectively. The blood flow of the arterialized portal vein to the graft was 1.8±0.3 ml/min/g liver weight. The success rate of model establishment (waking with post-surgical survival of >24 h) was 70% (7/10). Following successful model establishment, all rats survived 7 days post-surgery (100%; 7/7). The graft was found to be soft in texture and bright red in color following exploratory laparotomy. In conclusion, a new rat model of APHLT with LDABS without stent for vascular reconstruction was developed. This is a feasible and reliable rat model for liver transplantation study.

Atherosclerotic renal artery stenosis in the post-CORAL era part 1: the renal penumbra concept and next-generation functional diagnostic imaging.

PubMed

Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet

2016-04-01

After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Intra-operative hemodialysis during liver transplantation: an expanded role of the nephrology nurse.

PubMed

Henson, Angela; Carpenter, Sally

2010-01-01

Hemodialysis is widely acknowledged as a treatment option to stabilize acute medical conditions where biochemistry management is paramount. One of the most challenging situations is during liver transplantation, when patients with moderate renal dysfunction are likely to become acutely acidotic. For nephrology nurses, this extended role requires increased knowledge, advanced skills, and a high level of communication with unfamiliar team members. With appropriate procedures and a supportive environment, delivering such a service is feasible.

Food Poisonings by Ingestion of Cyprinid Fish

PubMed Central

Asakawa, Manabu; Noguchi, Tamao

2014-01-01

Raw or dried gallbladders of cyprinid fish have long been ingested as a traditional medicine in the Asian countries, particularly in China, for ameliorating visual acuity, rheumatism, and general health; however, sporadic poisoning incidences have occurred after their ingestion. The poisoning causes complex symptoms in patients, including acute renal failure, liver dysfunction, paralysis, and convulsions of limbs. The causative substance for the poisoning was isolated, and its basic properties were examined. The purified toxin revealed a minimum lethal dose of 2.6 mg/20 g in mouse, when injected intraperitoneally. The main symptoms were paralysis and convulsions of the hind legs, along with other neurological signs. Liver biopsy of the euthanized mice clearly exhibited hepatocytes necrosis and infiltration of neutrophils and lymphocytes, suggesting the acute dysfunction of the liver. Blood tests disclosed the characteristics of acute renal failure and liver injury. Infrared (IR) spectrometry, fast atom bombardment (FAB) mass spectrometry, and 1H- and 13C-nuclear magnetic resonance (NMR) analysis indicated, a molecular formula of C27H48O8S, containing a sulfate ester group for the toxin. Thus, we concluded that the structure of carp toxin to be 5α-cyprinol sulfate (5α-cholestane-3α, 7α, 12α, 26, 27-pentol 26-sulfate). This indicated that carp toxin is a nephro- and hepato- toxin, which could be the responsible toxin for carp bile poisoning in humans. PMID:24476713

Ameliorative Effect of Caffeic Acid on Capecitabine-Induced Hepatic and Renal Dysfunction: Involvement of the Antioxidant Defence System

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Adeyemo, Oluwatobi Adewumi

2017-01-01

Background: It has been postulated that during liver and kidney damage there is a decreased in the antioxidant status associated with a simultaneous increase in the reactive oxygen species and lipid peroxidation. In consonant with this, Capecitabine, an oral chemotherapy and inactive non-cytotoxic fluoropyrimidine considered for the treatment of advance colorectal cancer, has also been shown to induce oxidative stress in liver tissues. Caffeic acid, a typical hydroxycinnamic, has been claimed to be effective against oxidative stress. Therefore, this present work studied the protective effect of caffeic acid on oxidative stress-induced liver and kidney damage by the administration of capecitabine. Methods: Twenty-four male Wistar strain rats were randomly divided into four treatment groups: A. control, B. capecitabine (CPTB)-treated group (30 mg/kg b.w. CPTB), C. caffeic acid (CFA)-treated group (100 mg/kg b.w. CFA) and D. co-treated group with CFA (100 mg/kg b.w.) and CPTB (30 mg/kg b.w.). Results: Caffeic acid administration significantly ameliorated the elevated plasma biomarkers of hepatic and renal tissue damage induced by the capecitabine and improved enzymatic and non-enzymatic antioxidant levels in liver organ. Conclusions: The protective effect of caffeic acid could be attributed to its ability to boost the antioxidant defence system and reduce lipid peroxidation. PMID:29068374

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

PubMed

Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

2017-01-01

Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

Measuring residual renal function for hemodialysis adequacy: Is there an easier option?

PubMed

Davenport, Andrew

2017-10-01

Most patients starting hemodialysis (HD) have residual renal function. As such, there has been increased interest in starting patients with less frequent and shorter dialysis session times. However, for this incremental approach to be successful, patients require regular monitoring of residual renal function, so that as residual renal function declines, the amount of HD is appropriately increased. Currently most dialysis centers rely on interdialytic urine collections. However, many patients find these inconvenient and there may be marked intrapatient variability due to compliance issues. Thus, alternative markers of residual renal function are required for routine clinical practice. Currently three middle sized molecules; cystatin C, β2 microglobulin, and βtrace protein have been investigated as potential endogenous markers of glomerular filtration. Although none is ideal, combinations of these markers have been proposed to provide a more accurate estimation of glomerular clearance, and in particular cut offs for minimal residual renal function. However, in patients with low levels of residual renal function it remains unclear as to whether the benefits of residual renal function equally apply to glomerular filtration or tubular function. © 2017 International Society for Hemodialysis.

Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.

PubMed

Watts, Kara L; Ghosh, Propa; Stein, Solomon; Ghavamian, Reza

2017-01-01

To assess the relationship between individual nephrometry score (NS) constituents (RENAL) on perioperative outcomes and renal function of the surgical kidney in patients undergoing laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy. Two hundred forty-five patients who underwent laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each renal mass' NS was calculated from preoperative computed tomography imaging. Multivariate regression analysis was used to evaluate the effect of NS variables on perioperative outcomes and change in overall renal function (as estimated by glomerular filtration rate) from preoperative to 1-year postoperative. A cohort analysis assessed the effect of NS variables on change in split renal function of the surgical kidney from pre- to postoperative based on nuclear medicine renal scintigraphy. Tumor radius (R), endophytic nature (E), and nearness to collecting system (N) variables significantly and incrementally predicted a longer operative time and warm ischemia time. Overall renal function based on glomerular filtration rate was not affected by any NS variable. However, percent function of the surgical kidney by renal scintigraphy significantly decreased postoperatively as R and E values increased. R, E, and N were associated with significant changes in warm ischemia time and operative time. R and E were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery but not with overall renal function. R, E, and N are the NS constituents most relevant to perioperative outcomes and postoperative differential renal function after partial nephrectomy. Copyright © 2016. Published by Elsevier Inc.