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Sample records for early acute kidney

  1. Early detection of acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Jefferies, John Lynn; Devarajan, Prasad

    2016-01-01

    Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy. PMID:27429538

  2. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  3. Early and Late Acute Kidney Injury in Severely Burned Patients

    PubMed Central

    Witkowski, Wojciech; Kawecki, Marek; Surowiecka-Pastewka, Agnieszka; Klimm, Wojciech; Szamotulska, Katarzyna; Niemczyk, Stanisław

    2016-01-01

    Background This study evaluated factors influencing early and late occurrence of AKI in severely burned patients and assessed the relationship between time of occurrence of AKI and mortality of AKI patients. Material/Methods Renal function was evaluated at 3 time points: at admission, at the critical point or middle point of hospitalization, and at the endpoint for which death or a discharge from the center was considered. AKI criteria were: decrease in GFR of less than 60 ml/min at admission, decrease in GFR of more than 75% compared to baseline, and decrease in the daily diuresis of less than 500 ml/24 h. Results At admission, 15.1% of the patients had eGFR <60 ml/min. AKI occurred in 38.5% of cases. The occurrence of AKI was associated with: elderly age (p<0.001), female sex (p=0.017), overweight and obesity (p=0.055); extent and depth of burns, respiratory failure, low protein concentration (for all p<0.001), low blood pressure (p=0.014), and high WBC (p=0.010). Early AKI was detected in 28% of patients. Mortality was 100% with the initial GFR ≥60, 100% with the initial GFR <60 and early deterioration of renal function, 80% with the initial GFR <60 and late worsening, and 60% with the initial GFR <60 and no worsening. Late AKI was observed in 10% of patients and mortality in this group was 79.2%. Mortality in the entire group with AKI was 88.0% versus 24.5%. Conclusions The frequent occurrence of AKI, especially early, worsens the prognosis for survival. Assessment of renal function should be included in the prognostic scales for burned patients. PMID:27746455

  4. Pyruvate Kinase M2: A Novel Biomarker for the Early Detection of Acute Kidney Injury

    PubMed Central

    Cheon, Ji Hyun; Kim, Sun Young; Son, Ji Yeon; Kang, Ye Rim; An, Ji Hye; Kwon, Ji Hoon; Song, Ho Sub; Moon, Aree; Lee, Byung Mu; Kim, Hyung Sik

    2016-01-01

    The identification of biomarkers for the early detection of acute kidney injury (AKI) is clinically important. Acute kidney injury (AKI) in critically ill patients is closely associated with increased morbidity and mortality. Conventional biomarkers, such as serum creatinine (SCr) and blood urea nitrogen (BUN), are frequently used to diagnose AKI. However, these biomarkers increase only after significant structural damage has occurred. Recent efforts have focused on identification and validation of new noninvasive biomarkers for the early detection of AKI, prior to extensive structural damage. Furthermore, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Our previous study suggested that pyruvate kinase M2 (PKM2), which is excreted in the urine, is a sensitive biomarker for nephrotoxicity. To appropriately and optimally utilize PKM2 as a biomarker for AKI requires its complete characterization. This review highlights the major studies that have addressed the diagnostic and prognostic predictive power of biomarkers for AKI and assesses the potential usage of PKM2 as an early biomarker for AKI. We summarize the current state of knowledge regarding the role of biomarkers and the molecular and cellular mechanisms of AKI. This review will elucidate the biological basis of specific biomarkers that will contribute to improving the early detection and diagnosis of AKI. PMID:26977258

  5. Acute arterial occlusion - kidney

    MedlinePlus

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... main artery to the kidney is called the renal artery. Reduced blood flow through the renal artery ...

  6. [Ascites and acute kidney injury].

    PubMed

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years. PMID:27571467

  7. [Ascites and acute kidney injury].

    PubMed

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.

  8. Novel biomarkers for early diagnosis of acute kidney injury after cardiac surgery in adults

    PubMed Central

    Kališnik, Jurij Matija

    2016-01-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is a common and serious complication and it is associated with increased morbidity and mortality. Diagnosis of acute kidney injury is based on the serum creatinine levels which rise several hours to days after the initial injury. Thus, novel biomarkers that will enable faster diagnosis are needed in clinical practice. There are numerous urine and serum proteins that indicate kidney injury and are under extensive research. Despite promising basic research results and assembled data, which indicate superiority of some biomarkers to creatinine, we are still awaiting clinical application. PMID:27212976

  9. Acute kidney injury in children.

    PubMed

    Merouani, A; Flechelles, O; Jouvet, P

    2012-04-01

    Acute kidney injury (AKI) affects 5% of critically ill hospitalized children and is a risk factor for increased morbidity and mortality. The current review focuses on new definitions of acute kidney injury, standardized to reflect the entire spectrum of the disease, as well as on ongoing research to identify early biomarkers of kidney injury. Its also provides an overview of current practice and available therapies, with emphasis on new strategies for the prevention and pharmacological treatment of diarrhea-associated hemolytic uremic syndrome. Furthermore, a decision-making algorithm is presented for the use of renal replacement therapies in critically ill children with AKI. PMID:22495187

  10. Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury.

    PubMed

    Won, A Jin; Kim, Siwon; Kim, Yoon Gyoon; Kim, Kyu-Bong; Choi, Wahn Soo; Kacew, Sam; Kim, Kyeong Seok; Jung, Jee H; Lee, Byung Mu; Kim, Suhkmann; Kim, Hyung Sik

    2016-01-01

    The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-α (GST-α), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than

  11. Urinary Biomarkers TIMP-2 and IGFBP7 Early Predict Acute Kidney Injury after Major Surgery

    PubMed Central

    Gocze, Ivan; Koch, Matthias; Renner, Philipp; Zeman, Florian; Graf, Bernhard M.; Dahlke, Marc H.; Nerlich, Michael; Schlitt, Hans J.; Kellum, John A.; Bein, Thomas

    2015-01-01

    Objective To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7) and TIMP-2 (tissue inhibitor of metalloproteinase 2) to early predict acute kidney injury (AKI) in high-risk surgical patients. Introduction Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function. Methods In this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test. Results 107 patients were included in the study, of whom 45 (42%) developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l2/1000). The area under receiving operating characteristic curve (AUC) for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001). Conclusions Urinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major non-cardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI. PMID:25798585

  12. Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

    PubMed

    Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

    2016-11-01

    Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine.

  13. Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

    PubMed

    Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

    2016-11-01

    Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine. PMID:27485279

  14. Advances in acute kidney injury associated with cardiac surgery: the unfolding revolution in early detection.

    PubMed

    Wyckoff, Tygh; Augoustides, John G T

    2012-04-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is important because it remains common and serious. A major limitation in the management of CSA-AKI has been ongoing delayed diagnosis by standard clinical approaches, including serum creatinine and calculated glomerular filtration rate. Recent advances in the understanding of CSA-AKI have highlighted the utility of novel biomarkers that diagnose CSA-AKI within the first 24 hours. The biomarkers that have been evaluated in clinical trials include neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule 1 and interleukin-18. The biomarker with the greatest clinical promise is NGAL. Although it has multiple advantages over serum creatinine, it is still not the ideal biomarker for CSA-AKI. It is likely that a panel of early biomarkers will be developed to facilitate rapid and reliable detection of CSA-AKI, combining their different characteristics to optimize patient management. Future clinical trials likely will focus on whether these biomarkers predict adverse outcomes independent of serum creatinine fluctuations and whether therapies guided by biomarker profiles improve renal salvage and overall clinical outcomes. Given their clinical utility, these novel biomarkers have been evaluated beyond cardiac surgery for AKI in multiple clinical environments, including the emergency department, the operating room, the cardiac catheterization laboratory, and the intensive care unit. Their integration into clinical practice seems likely in the near future.

  15. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury.

    PubMed

    Parr, Sharidan K; Clark, Amanda J; Bian, Aihua; Shintani, Ayumi K; Wickersham, Nancy E; Ware, Lorraine B; Ikizler, T Alp; Siew, Edward D

    2015-03-01

    Biomarker studies for early detection of acute kidney injury (AKI) have been limited by nonselective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of 152 patients with known baseline creatinine examined, 36 experienced the composite outcome. Urine L-FABP demonstrated an area under the receiver-operating characteristic curve (AUC-ROC) of 0.79 (95% confidence interval 0.70-0.86), which improved to 0.82 (95% confidence interval 0.75-0.90) when added to the clinical model (AUC-ROC of 0.74). Urine NGAL, IL-18, and KIM-1 had AUC-ROCs of 0.65, 0.64, and 0.62, respectively, but did not significantly improve discrimination of the clinical model. The category-free net reclassification index improved with urine L-FABP (total net reclassification index for nonevents 31.0%) and urine NGAL (total net reclassification index for events 33.3%). However, only urine L-FABP significantly improved the integrated discrimination index. Thus, modest early changes in serum creatinine can help target biomarker measurement for determining prognosis with urine L-FABP, providing independent and additive prognostic information when combined with clinical predictors.

  16. Development of a MALDI MS‐based platform for early detection of acute kidney injury

    PubMed Central

    Vanmassenhove, Jill; Glorieux, Griet; Metzger, Jochen; Dakna, Mohammed; Pejchinovski, Martin; Jankowski, Vera; Mansoorian, Bahareh; Husi, Holger; Mullen, William; Mischak, Harald; Vanholder, Raymond; Van Biesen, Wim

    2016-01-01

    1 Purpose Septic acute kidney injury (AKI) is associated with poor outcome. This can partly be attributed to delayed diagnosis and incomplete understanding of the underlying pathophysiology. Our aim was to develop an early predictive test for AKI based on the analysis of urinary peptide biomarkers by MALDI‐MS. 2 Experimental design Urine samples from 95 patients with sepsis were analyzed by MALDI‐MS. Marker search and multimarker model establishment were performed using the peptide profiles from 17 patients with existing or within the next 5 days developing AKI and 17 with no change in renal function. Replicates of urine sample pools from the AKI and non‐AKI patient groups and normal controls were also included to select the analytically most robust AKI markers. 3 Results Thirty‐nine urinary peptides were selected by cross‐validated variable selection to generate a support vector machine multidimensional AKI classifier. Prognostic performance of the AKI classifier on an independent validation set including the remaining 61 patients of the study population (17 controls and 44 cases) was good with an area under the receiver operating characteristics curve of 0.82 and a sensitivity and specificity of 86% and 76%, respectively. 4 Conclusion and clinical relevance A urinary peptide marker model detects onset of AKI with acceptable accuracy in septic patients. Such a platform can eventually be transferred to the clinic as fast MALDI‐MS test format. PMID:27119821

  17. Assessment of Plasma and NGAL for the Early Prediction of Acute Kidney Injury After Cardiac Surgery in Adults Study

    ClinicalTrials.gov

    2016-04-11

    Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)

  18. Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

    NASA Astrophysics Data System (ADS)

    Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

    2014-06-01

    We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

  19. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats.

  20. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  1. Assessment of Cell-Cycle Arrest Biomarkers to Predict Early and Delayed Acute Kidney Injury

    PubMed Central

    Bell, Max; Larsson, Anders; Venge, Per; Bellomo, Rinaldo; Mårtensson, Johan

    2015-01-01

    Purpose. To assess urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein 7 ([TIMP-2]·[IGFBP7]), urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary cystatin-C as acute kidney injury predictors (AKI) exploring the association of nonrenal factors with elevated biomarker levels. Methods. We studied 94 patients with urine collected within 48 hours of ICU admission and no AKI at sampling. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Predictive performance was assessed by the area under the receiver operating characteristics (ROC) curve. Associations between biomarkers and clinical factors were assessed by multivariate linear regression. Results. Overall, 19 patients (20%) developed AKI within 48 hours. [TIMP-2]·[IGFBP7], NGAL, or cystatin-C admission levels did not differ between patients without AKI and patients developing AKI. [TIMP-2]·[IGFBP7], NGAL, and cystatin-C were poor AKI predictors (ROC areas 0.34–0.51). Diabetes was independently associated with higher [TIMP-2]·[IGFBP7] levels (P = 0.02) but AKI was not (P = 0.24). Sepsis was independently associated with higher NGAL (P < 0.001) and cystatin-C (P = 0.003) levels. Conclusions. Urinary [TIMP-2]·[IGFBP7], NGAL, and cystatin-C should be used cautiously as AKI predictors in general ICU patients since urine levels of these biomarkers are affected by factors other than AKI and their performance can be poor. PMID:25866432

  2. Acute Kidney Injury.

    PubMed

    Zuk, Anna; Bonventre, Joseph V

    2016-01-01

    Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD).

  3. Astaxanthin Attenuates Early Acute Kidney Injury Following Severe Burns in Rats by Ameliorating Oxidative Stress and Mitochondrial-Related Apoptosis

    PubMed Central

    Guo, Song-Xue; Zhou, Han-Lei; Huang, Chun-Lan; You, Chuan-Gang; Fang, Quan; Wu, Pan; Wang, Xin-Gang; Han, Chun-Mao

    2015-01-01

    Early acute kidney injury (AKI) is a devastating complication in critical burn patients, and it is associated with severe morbidity and mortality. The mechanism of AKI is multifactorial. Astaxanthin (ATX) is a natural compound that is widely distributed in marine organisms; it is a strong antioxidant and exhibits other biological effects that have been well studied in various traumatic injuries and diseases. Hence, we attempted to explore the potential protection of ATX against early post burn AKI and its possible mechanisms of action. The classic severe burn rat model was utilized for the histological and biochemical assessments of the therapeutic value and mechanisms of action of ATX. Upon ATX treatment, renal tubular injury and the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were improved. Furthermore, relief of oxidative stress and tubular apoptosis in rat kidneys post burn was also observed. Additionally, ATX administration increased Akt and Bad phosphorylation and further down-regulated the expression of other downstream pro-apoptotic proteins (cytochrome c and caspase-3/9); these effects were reversed by the PI3K inhibitor LY294002. Moreover, the protective effect of ATX presents a dose-dependent enhancement. The data above suggested that ATX protects against early AKI following severe burns in rats, which was attributed to its ability to ameliorate oxidative stress and inhibit apoptosis by modulating the mitochondrial-apoptotic pathway, regarded as the Akt/Bad/Caspases signalling cascade. PMID:25871290

  4. Early postoperative albumin level following total knee arthroplasty is associated with acute kidney injury

    PubMed Central

    Kim, Ha-Jung; Koh, Won-Uk; Kim, Sae-Gyeol; Park, Hyeok-Seong; Song, Jun-Gol; Ro, Young-Jin; Yang, Hong-Seuk

    2016-01-01

    Abstract Hypoalbuminemia has been reported to be an independent risk factor for acute kidney injury (AKI). However, little is known about the relationship between the albumin level and the incidence of AKI in patients undergoing total knee arthroplasty (TKA). The aim of our study was to assess incidence and risk factors for AKI and to evaluate the relationship between albumin level and AKI following TKA. The study included a retrospective review of medical records of 1309 consecutive patients who underwent TKA between January 2008 and December 2014. The patients were divided into 2 groups according to the lowest serum albumin level within 2 postoperative days (POD2_alb level < 3.0 g/dL vs ≥3.0 g/dL). Multivariate logistic regression analysis was used to assess risk factors for AKI. A comparison of incidence of AKI, hospital stay, and overall mortality in the 2 groups was performed using propensity score analysis. Of 1309 patients, 57 (4.4%) developed AKI based on Kidney Disease Improving Global Outcomes criteria. Factors associated with AKI included age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.01–1.09; P = 0.030), diabetes (OR 3.12; 95% CI 1.65–5.89; P < 0.001), uric acid (OR 1.51; 95% CI 1.26–1.82; P < 0.001), beta blocker use (OR 2.65; 95% CI 1.48–4.73; P = 0.001), diuretics (OR 16.42; 95% CI 3.08–87.68; P = 0.001), and POD2_alb level < 3.0 g/dL (OR 1.92; 95% CI 1.09–3.37; P = 0.023). After propensity score analysis, POD2_alb level<3.0 g/dL was associated with AKI occurrence (OR 1.82; 95% CI 1.03–3.24, P = 0.041) and longer hospital stay (P = 0.001). In this study, we demonstrated that POD2_alb level<3.0 g/dL was an independent risk factor for AKI and lengthened hospital stay in patients undergoing TKA. PMID:27495094

  5. Acute kidney injury due to decompression illness

    PubMed Central

    Viecelli, Andrea; Jamboti, Jagadish; Waring, Andrew; Banham, Neil; Ferrari, Paolo

    2014-01-01

    Decompression illness is a rare but serious complication of diving caused by intravascular or extravascular gas bubble formation. We report the first case of acute kidney injury in a 27-year-old diver following three rapid ascents. He presented with transient neurological symptoms and abdominal pain followed by rapidly progressive acute kidney injury (creatinine peak 1210 µmol/L) due to arterial air emboli. He received supportive care and 100% oxygen followed by hyperbaric therapy and recovered fully. Arterial air emboli caused by rapid decompression can affect multiple organs including the kidneys. Early transfer to a hyperbaric unit is important as complications may present delayed. PMID:25852912

  6. Perioperative acute kidney injury.

    PubMed

    Goren, O; Matot, I

    2015-12-01

    Perioperative acute kidney injury (AKI) is not uncommon and is associated with considerable morbidity and mortality. Recently, several definition systems for AKI were proposed, incorporating both small changes of serum creatinine and urinary output reduction as diagnostic criteria. Novel biomarkers are under investigation as fast and accurate predictors of AKI. Several special considerations regarding the risk of AKI are of note in the surgical patient. Co-morbidities are important risk factors for AKI. The surgery in itself, especially emergency and major surgery in the critically ill, is associated with a high incidence of AKI. Certain types of surgeries, such as cardiac and transplantation surgeries, require special attention because they carry higher risk of AKI. Nephrotoxic drugs, contrast dye, and diuretics are commonly used in the perioperative period and are responsible for a significant amount of in-hospital AKI. Before surgery, the anaesthetist is required to identify patients at risk of AKI, optimize anaemia, and treat hypovolaemia. During surgery, normovolaemia is of utmost importance. Additionally, the surgical and anaesthesia team is advised to use measures to reduce blood loss and avoid unnecessary blood transfusion. Hypotension should be avoided because even short periods of mean arterial pressure <55-60 mm Hg carry a risk of postoperative AKI. Higher blood pressures are probably required for hypertensive patients. Urine output can be reduced significantly during surgery and is unrelated to perioperative renal function. Thus, fluids should not be given in excess for the sole purpose of avoiding or treating oliguria. Use of hydroxyethyl starch needs to be reconsidered. Recent evidence indicates a beneficial effect of administering low-chloride solutions. PMID:26658199

  7. Potential biomarkers for the early detection of acute kidney injury after percutaneous nephrolithotripsy.

    PubMed

    Daggülli, Mansur; Utangaç, Mehmet M; Dede, Onur; Bodakci, Mehmet N; Hatipoglu, Namık K; Penbegül, Necmettin; Sancaktutar, Ahmet A; Bozkurt, Yaşar; Söylemez, Haluk

    2016-01-01

    This study aims to investigate the role of urinary biomarkers in the determination of the potential risks of renal parenchymal tubular damage in adult patients who underwent percutaneous nephrolithotomy (PNL) with the indication of renal stone. A randomized and prospective controlled study was performed between June and December 2013. We enrolled 29 consecutive patients with renal calculi > 2 cm and who underwent PNL, as well as 47 healthy control subjects. Urine samples, including 2 h before surgery, 2 and 24 h after surgery were collected from the patient group. Freshly voided urine samples were collected from the control group. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-glucosaminidase (NAG), and liver-type fatty acid binding protein (LFABP) levels were measured from these urine samples. The mean KIM-1/Cr value that measured 24 h after the operation was statistically significant, higher than its preoperative (preop) level (p = 0.045). A significant difference was detected between the mean preop and postoperative (postop) 24 h NAG/Cr values (p < 0.001). Also, postop 24 h NGAL/Cr levels were statistically significant, higher than its preop levels (p = 0.013). According to the comparison of preop and postop levels, an increase in LFABP/Cr values secondary to surgical intervention was observed without any statistically significant difference. Besides the LFABP/Cr levels do not change after percutaneous kidney surgery, KIM-1/Cr, NAG/Cr, and NGAL/Cr levels increase postop period, especially at 24 h. Further studies with a larger series and repeated measurements should be performed to clarify if they can be used to demonstrate renal damage after percutaneous surgery or not. PMID:26481764

  8. Acute kidney injury after pediatric cardiac surgery.

    PubMed

    Singh, Sarvesh Pal

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074

  9. Acute Kidney Injury in the Elderly

    PubMed Central

    Abdel-Kader, Khaled; Palevsky, Paul

    2009-01-01

    Synopsis The aging kidney undergoes a number of important anatomic and physiologic changes that increase the risk of acute kidney injury (formerly acute renal failure) in the elderly. This article reviews these changes and discusses the diagnoses frequently encountered in the elderly patient with acute kidney injury. The incidence, staging, evaluation, management, and prognosis of acute kidney injury are also examined with special focus given to older adults. PMID:19765485

  10. The cell cycle and acute kidney injury.

    PubMed

    Price, Peter M; Safirstein, Robert L; Megyesi, Judit

    2009-09-01

    Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute kidney injury.

  11. Cardiac surgery-associated acute kidney injury.

    PubMed

    Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio

    2013-10-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314

  12. Targeting Iron Homeostasis in Acute Kidney Injury.

    PubMed

    Walker, Vyvyca J; Agarwal, Anupam

    2016-01-01

    Iron is an essential metal involved in several major cellular processes required to maintain life. Because of iron's ability to cause oxidative damage, its transport, metabolism, and storage is strictly controlled in the body, especially in the small intestine, liver, and kidney. Iron plays a major role in acute kidney injury and has been a target for therapeutic intervention. However, the therapies that have been effective in animal models of acute kidney injury have not been successful in human beings. Targeting iron trafficking via ferritin, ferroportin, or hepcidin may offer new insights. This review focuses on the biology of iron, particularly in the kidney, and its implications in acute kidney injury. PMID:27085736

  13. Epigenetics in acute kidney injury

    PubMed Central

    Tang, Jinhua; Zhuang, Shougang

    2015-01-01

    Purpose of review Recent advances in epigenetics indicate the involvement of several epigenetic modifications in the pathogenesis of acute kidney injury (AKI). The purpose of this review is to summarize our understanding of recent advances in epigenetic regulation of AKI and provide mechanistic insight into the role of acetylation, methylation, and microRNA expression in the pathological processes of AKI. Recent findings Enhancement of protein acetylation by pharmacological inhibition of histone deacetylases (HDACs) leads to more severe tubular injury and impairment of renal structural and functional recovery. The changes in promoter DNA methylation occur in the kidney with ischemia/reperfusion. microRNA expression is associated with regulation of both renal injury and regeneration after AKI. Summary Recent studies on epigenetic regulation indicate that acetylation, methylation, and microRNA expression are critically implicated in the pathogenesis of AKI. Strategies targeting epigenetic processes may hold a therapeutic potential for patients with AKI. PMID:26050122

  14. Distinct injury markers for the early detection and prognosis of incident acute kidney injury in critically ill adults with preserved kidney function

    PubMed Central

    Siew, Edward D.; Ware, Lorraine B.; Bian, Aihua; Shintani, Ayumi; Eden, Svetlana; Wickersham, Nancy; Cripps, Ben; Ikizler, T. Alp

    2013-01-01

    The use of novel biomarkers to detect incident acute kidney injury (AKI) in the critically ill is hindered by heterogeneity of injury and the potentially confounding effects of prevalent AKI. Here we examined the ability of urine NGAL (NGAL), L-type Fatty Acid Binding Protein (L-FABP), and Cystatin C to predict AKI development, death, and dialysis in a nested case-control study of 380 critically ill adults with an eGFR over 60 ml/min/1.73 m2. One-hundred thirty AKI cases were identified following biomarker measurement and were compared to 250 controls without AKI. Areas under the receiver-operator characteristic curves (AUC-ROCs) for discriminating incident AKI from non-AKI were 0.58(95%CI: 0.52-0.64), 0.59(0.52-0.65), and 0.50(0.48-0.57) for urine NGAL, L-FABP, and Cystatin C, respectively. The combined AUC-ROC for NGAL and L-FABP was 0.59(56-0.69). Both urine NGAL and L-FABP independently predicted AKI during multivariate regression; however, risk reclassification indices were mixed. Neither urine biomarker was independently associated with death or acute dialysis [NGAL hazard ratio 1.35(95%CI: 0.93-1.96), L-FABP 1.15(0.82-1.61)] though both independently predicted the need for acute dialysis [NGAL 3.44(1.73-6.83), L-FABP 2.36(1.30-4.25)]. Thus, urine NGAL and L-FABP independently associated with the development of incident AKI and receipt of dialysis but exhibited poor discrimination for incident AKI using conventional definitions. PMID:23698227

  15. Nephrology Update: Acute Kidney Injury.

    PubMed

    Sarabu, Nagaraju; Rahman, Mahboob

    2016-05-01

    Acute kidney injury (AKI) refers to any acute decrease in glomerular filtration rate, regardless of etiology. Staging of AKI has been recommended to stratify AKI patients according to severity of the condition, based on serum creatinine level and urine output. Classification of AKI into prerenal, intrinsic renal, and postrenal etiologies is helpful in differential diagnosis and management. AKI in hospitalized patients typically occurs due to decreased renal perfusion. Drug-induced, contrast-associated, postoperative, and sepsis-associated AKI also can occur. Clinical assessment of a patient with AKI involves a medical record review, thorough history and physical examination, urinary and blood tests, renal imaging, and, in some instances, renal biopsy. Contrast-induced nephropathy is a common iatrogenic etiology of AKI associated with administration of intravenous iodinated contrast media. Measures to prevent AKI should be taken before administration of intravenous iodinated contrast. AKI can result in many short- and long-term complications, including chronic kidney disease and end-stage renal disease. Appropriate treatment of AKI patients involves management of the underlying etiology, when possible, and use of nondialytic and dialytic therapies. PMID:27163760

  16. Apoptosis and acute kidney injury

    PubMed Central

    Havasi, Andrea; Borkan, Steven C.

    2015-01-01

    Improved mechanistic understanding of renal cell death in acute kidney injury (AKI) has generated new therapeutic targets. Clearly, the classic lesion of acute tubular necrosis is not adequate to describe the consequences of renal ischemia, nephrotoxin exposure, or sepsis on glomerular filtration rate. Experimental evidence supports a pathogenic role for apoptosis in AKI. Interestingly, proximal tubule epithelial cells are highly susceptible to apoptosis, and injury at this site contributes to organ failure. During apoptosis, well-orchestrated events converge at the mitochondrion, the organelle that integrates life and death signals generated by the BCL2 (B-cell lymphoma 2) protein family. Death requires the ‘perfect storm’ for outer mitochondrial membrane injury to release its cellular ‘executioners’. The complexity of this process affords new targets for effective interventions, both before and after renal insults. Inhibiting apoptosis appears to be critical, because circulating factors released by the injured kidney induce apoptosis and inflammation in distant organs including the heart, lung, liver, and brain, potentially contributing to the high morbidity and mortality associated with AKI. Manipulation of known stress kinases upstream of mitochondrial injury, induction of endogenous, anti-apoptotic proteins, and improved understanding of the timing and consequences of renal cell apoptosis will inevitably improve the outcome of human AKI. PMID:21562469

  17. Sepsis-induced acute kidney injury.

    PubMed

    Majumdar, Arghya

    2010-01-01

    Acute kidney injury (AKI) is a common sequel of sepsis in the intensive care unit. It is being suggested that sepsis-induced AKI may have a distinct pathophysiology and identity. Availability of biomarkers now enable us to detect AKI as early as four hours after it's inception and may even help us to delineate sepsis-induced AKI. Protective strategies such as preferential use of vasopressin or prevention of intra-abdominal hypertension may help, in addition to the other global management strategies of sepsis. Pharmacologic interventions have had limited success, may be due to their delayed usage. Newer developments in extracorporeal blood purification techniques may proffer effects beyond simple replacement of renal function, such as metabolic functions of the kidney or modulation of the sepsis cascade.

  18. Kidney Disease: Early Detection and Treatment

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Kidney Disease: Early Detection and Treatment Past Issues / Winter ... called a "urine albumin-to-creatinine ratio." Treating Kidney Disease Kidney disease is usually a progressive disease, ...

  19. Pathophysiology of Acute Kidney Injury

    PubMed Central

    Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.

    2014-01-01

    Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. PMID:23798302

  20. Biomarkers in acute kidney injury: Evidence or paradigm?

    PubMed

    Lombi, Fernando; Muryan, Alexis; Canzonieri, Romina; Trimarchi, Hernán

    2016-01-01

    Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.

  1. Effects of Valproic Acid and Dexamethasone Administration on Early Bio-Markers and Gene Expression Profile in Acute Kidney Ischemia-Reperfusion Injury in the Rat

    PubMed Central

    Speir, Ryan W.; Stallings, Jonathan D.; Andrews, Jared M.; Gelnett, Mary S.; Brand, Timothy C.; Salgar, Shashikumar K.

    2015-01-01

    Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (saline) intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL) at 24 h was reduced (P<0.05) in VPA (2.7±1.8) and Dex (2.3±1.2) compared to Vehicle (3.8±0.5) group. At 3 h, urine albumin (mg/mL) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to naïve (uninjured/untreated control) (0.14±0.26) group. At 24 h post-IR urine lipocalin-2 (μg/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (9.61–11.36) compared to naïve group (0.67±0.29); also, kidney injury molecule-1 (KIM-1; ng/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (13.7–18.7) compared to naïve group (1.7±1.9). Histopathology demonstrated reduced (P<0.05) ischemic injury in the renal cortex in VPA (Grade 1.6±1.5) compared to Vehicle (Grade 2.9±1.1). Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI. PMID:25970334

  2. Contrast-associated Acute Kidney Injury.

    PubMed

    Weisbord, Steven D; Palevsky, Paul M

    2015-10-01

    Contrast-associated acute kidney injury (CAAKI) is a common iatrogenic condition. The principal risk factors for CAAKI are underlying renal impairment; diabetes in the setting of kidney disease; and intravascular volume depletion, effective or absolute. CAAKI is associated with serious adverse short-term and long-term outcomes, including mortality and more rapidly progressive chronic kidney disease, although the causal nature of these associations remains unproved. Patients with chronic kidney disease and other risk factors for CAAKI who present with acute coronary syndrome should undergo indicated angiographic procedures.

  3. Ischemic Acute Kidney Injury Perturbs Homeostasis of Serine Enantiomers in the Body Fluid in Mice: Early Detection of Renal Dysfunction Using the Ratio of Serine Enantiomers

    PubMed Central

    Sasabe, Jumpei; Suzuki, Masataka; Miyoshi, Yurika; Tojo, Yosuke; Okamura, Chieko; Ito, Sonomi; Konno, Ryuichi; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu

    2014-01-01

    The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little D-serine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D−/L-serine from 2.82±0.18 to 1.10±0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D−/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D−/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury. PMID:24489731

  4. Acute Kidney Injury is More Common in Acute Haemorrhagic Stroke in Mymensingh Medical College Hospital.

    PubMed

    Ray, N C; Chowdhury, M A; Sarkar, S R

    2016-01-01

    Acute kidney injury (AKI) is a common complication after acute stroke and is an independent predictor of both early and long-term mortality after acute stroke. Acute kidney injury is associated with increased mortality in haemorrhagic stroke patients. This cross sectional observational study was conducted in Nephrology, Neuromedicine and Medicine department of Mymensingh Medical College & Hospital, Mymensingh from July 2012 to June 2014. A total of 240 patients with newly detected acute stroke confirmed by CT scan of brain were included in this study. According to this study, 15.42% of acute stroke patients developed AKI. Among the patients with haemorrhagic stroke 21.87% developed AKI while only 13.07% patients with ischaemic stroke developed AKI. So, early diagnosis and management of AKI in patients with acute stroke especially in haemorrhagic stroke is very important to reduce the morbidity and mortality of these patients. PMID:26931240

  5. Blocking TGF-β Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRβ+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats

    PubMed Central

    Pozdzik, Agnieszka A.; Giordano, Laetitia; Li, Gang; Antoine, Marie-Hélène; Quellard, Nathalie; Godet, Julie; De Prez, Eric; Husson, Cécile; Declèves, Anne-Emilie; Arlt, Volker M.; Goujon, Jean-Michel; Brochériou-Spelle, Isabelle; Ledbetter, Steven R.; Caron, Nathalie; Nortier, Joëlle L.

    2016-01-01

    Background The platelet-derived growth factor receptor β (PDGFRβ)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target. Aims In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ) inhibition in a rat model of AAN. Materials and Methods Neutralizing anti-TGFβ antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily. Results At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro. Conclusions The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation. PMID:27379382

  6. Acute kidney injury due to rhabdomyolysis.

    PubMed

    Lima, Rafael Siqueira Athayde; da Silva Junior, Geraldo Bezerra; Liborio, Alexandre Braga; Daher, Elizabeth De Francesco

    2008-09-01

    Rhabdomyolysis is a clinical and biochemical syndrome that occurs when skeletal muscle cells disrupt and release creatine phosphokinase (CK), lactate dehydrogenase (LDH), and myoglobin into the interstitial space and plasma. The main causes of rhabdomyolysis include direct muscular injury, strenuous exercise, drugs, toxins, infections, hyperthermia, seizures, meta-bolic and/or electrolyte abnormalities, and endocrinopathies. Acute kidney injury (AKI) occurs in 33-50% of patients with rhabdomyolysis. The main pathophysiological mechanisms of renal injury are renal vasoconstriction, intraluminal cast formation, and direct myoglobin toxicity. Rhabdo-myolysis can be asymptomatic, present with mild symptoms such as elevation of muscular en-zymes, or manifest as a severe syndrome with AKI and high mortality. Serum CK five times higher than the normal value usually confirms rhabdomyolysis. Early diagnosis and saline volume expansion may reduce the risk of AKI. Further studies are necessary to establish the importance of bicarbonate and mannitol in the prevention of AKI due to rhabdomyolysis. PMID:18711286

  7. [Perioperative acute kidney injury and failure].

    PubMed

    Chhor, Vibol; Journois, Didier

    2014-04-01

    Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance.

  8. Cardiac surgery-associated acute kidney injury

    PubMed Central

    Ortega-Loubon, Christian; Fernández-Molina, Manuel; Carrascal-Hinojal, Yolanda; Fulquet-Carreras, Enrique

    2016-01-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized complication resulting with the higher morbid-mortality after cardiac surgery. In its most severe form, it increases the odds ratio of operative mortality 3–8-fold, length of stay in the Intensive Care Unit and hospital, and costs of care. Early diagnosis is critical for an optimal treatment of this complication. Just as the identification and correction of preoperative risk factors, the use of prophylactic measures during and after surgery to optimize renal function is essential to improve postoperative morbidity and mortality of these patients. Cardiopulmonary bypass produces an increased in tubular damage markers. Their measurement may be the most sensitive means of early detection of AKI because serum creatinine changes occur 48 h to 7 days after the original insult. Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 are most promising as an early diagnostic tool. However, the ideal noninvasive, specific, sensitive, reproducible biomarker for the detection of AKI within 24 h is still not found. This article provides a review of the different perspectives of the CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment. We searched the electronic databases, MEDLINE, PubMed, EMBASE using search terms relevant including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment, in order to provide an exhaustive review of the different perspectives of the CSA-AKI. PMID:27716701

  9. Computerized clinical decision support for the early recognition and management of acute kidney injury: a qualitative evaluation of end-user experience

    PubMed Central

    Kanagasundaram, Nigel S.; Bevan, Mark T.; Sims, Andrew J.; Heed, Andrew; Price, David A.; Sheerin, Neil S.

    2016-01-01

    Background Although the efficacy of computerized clinical decision support (CCDS) for acute kidney injury (AKI) remains unclear, the wider literature includes examples of limited acceptability and equivocal benefit. Our single-centre study aimed to identify factors promoting or inhibiting use of in-patient AKI CCDS. Methods Targeting medical users, CCDS triggered with a serum creatinine rise of ≥25 μmol/L/day and linked to guidance and test ordering. User experience was evaluated through retrospective interviews, conducted and analysed according to Normalization Process Theory. Initial pilot ward experience allowed tool refinement. Assessments continued following CCDS activation across all adult, non-critical care wards. Results Thematic saturation was achieved with 24 interviews. The alert was accepted as a potentially useful prompt to early clinical re-assessment by many trainees. Senior staff were more sceptical, tending to view it as a hindrance. ‘Pop-ups’ and mandated engagement before alert dismissal were universally unpopular due to workflow disruption. Users were driven to close out of the alert as soon as possible to review historical creatinines and to continue with the intended workflow. Conclusions Our study revealed themes similar to those previously described in non-AKI settings. Systems intruding on workflow, particularly involving complex interactions, may be unsustainable even if there has been a positive impact on care. The optimal balance between intrusion and clinical benefit of AKI CCDS requires further evaluation. PMID:26798462

  10. Acute kidney injury with hypoxic respiratory failure

    PubMed Central

    Neubert, Zachary; Hoffmann, Paul; Owshalimpur, David

    2014-01-01

    A 27-year-old Caucasian man was transferred from a remote clinic with acute kidney injury for the prior 7–10 days preceded by gastroenteritis. His kidney biopsy showed non-specific mesangiopathic glomerular changes, minimal tubulointerstitial disease without sclerosis, crescents, nor evidence of vasculitis. On his third hospital day, he developed acute hypoxic respiratory failure requiring intubation and mechanical ventilation. Pulmonary renal syndromes ranked highest on his differential diagnosis. He was extubated after 2 days of mechanical ventilation and after pulse dose steroids. His lung biopsy showed pulmonary capillaritis. Our case describes a patient with clinically appearing renopulmonary syndrome, but found to have pulmonary capillaritis, a rare form of lung disease that may also cause acute kidney injury. PMID:25246473

  11. Early diabetic kidney maintains the corticomedullary urea and sodium gradient.

    PubMed

    Qi, Haiyun; Nørlinger, Thomas S; Nielsen, Per M; Bertelsen, Lotte B; Mikkelsen, Emmeli; Xu, Yafang; Stødkilde Jørgensen, Hans; Laustsen, Christoffer

    2016-03-01

    Early diabetic nephropathy is largely undetectable before substantial functional changes have occurred. In the present study, we investigated the distribution of electrolytes and urea in the early diabetic kidney in order to explore whether pathophysiological and metabolic changes appear concomitantly with a decreased sodium and urea gradient. By using hyperpolarized (13)C urea it was possible to measure the essential intrarenal electrolyte gradients and the acute changes following furosemide treatment. No differences in either intrarenal urea or sodium gradients were observed in early diabetes compared to healthy controls. These results indicate that the early metabolic and hypertrophic changes occurring in the diabetic kidney prelude the later functional alterations in diabetic kidney function, thus driving the increased metabolic demand commonly occurring in the diabetic kidney.

  12. Acute Kidney Injury Associated with Linagliptin.

    PubMed

    Nandikanti, Deepak K; Gosmanova, Elvira O; Gosmanov, Aidar R

    2016-01-01

    Linagliptin is a dipeptidyl peptidase-IV (DPP-IV) inhibitor that is approved for the treatment of type 2 diabetes mellitus. About 5% of linagliptin is eliminated by the kidneys and no dose adjustment is recommended in kidney impairment. We report a first case of linagliptin-associated acute kidney injury (AKI) in a patient with preexisting chronic kidney disease (CKD). We hypothesize that AKI was due to renal hypoperfusion from linagliptin-induced natriuresis and intravascular volume contraction in the setting of concomitant lisinopril use, which is known to impair autoregulation and potentiate hypotension-induced AKI. It may be prudent to exert caution and closely monitor kidney function when initiating linagliptin in combination with ACE-inhibitors in CKD patients. PMID:26981294

  13. Pathophysiology and Clinical Work-Up of Acute Kidney Injury.

    PubMed

    Meola, Mario; Nalesso, Federico; Petrucci, Ilaria; Samoni, Sara; Ronco, Claudio

    2016-01-01

    Acute kidney injury (AKI), also known in the past as acute renal failure, is a syndrome characterized by the rapid loss of kidney excretory function. It is usually diagnosed by the accumulation of end products of nitrogen metabolism (urea and creatinine) or decreased urine output or both. AKI is the clinical consequence of several disorders that acutely affect the kidney, causing electrolytes and acid-base imbalance, hyperhydration and loss of depurative function. AKI is common in critical care patients in whom it is often secondary to extrarenal events. No specific therapies can attenuate AKI or accelerate renal function recovery; thus, the only treatment is supportive. New diagnostic techniques such as renal biomarkers might improve early diagnosis. Also ultrasonography helps nephrologists in AKI diagnosis, in order to describe and follow kidney alterations and find possible causes of AKI. Renal replacement therapy is a life-saving treatment if AKI is severe. If patients survive to AKI, and did not have previous chronic kidney disease (CKD), they typically recover to dialysis independence. However, evidence suggests that patients who have had AKI are at increased risk of subsequent CKD. PMID:27169469

  14. Early predictors of acute kidney injury in patients with cirrhosis and bacterial infection: urinary neutrophil gelatinase-associated lipocalin and cardiac output as reliable tools

    PubMed Central

    Ximenes, Rafael O.; Farias, Alberto Q.; Helou, Claudia M.B.

    2015-01-01

    Background Hemodynamic abnormalities and acute kidney injury (AKI) are often present in infected cirrhotic patients. Hence, an early diagnosis of AKI is necessary, which might require the validation of new predictors as the determinations of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and cardiac output. Methods We evaluated 18 infected cirrhotic patients subdivided into two groups at admission (0 hours). In Group I, we collected urine samples at 0 hours, 6 hours, 24 hours, and 48 hours for uNGAL and fractional excretion of sodium determinations. In Group II, we measured cardiac output using echocardiography. Results The age of patients was 55.0±1.9 years, and 11 patients were males. The Model for End-Stage Liver Disease score was 21±1, whereas the Child–Pugh score was C in 11 patients and B in 7 patients. Both patients in Group I and Group II showed similar baseline characteristics. In Group I, we diagnosed AKI in 5 of 9 patients, and the mean time to this diagnosis by measuring serum creatinine was 5.4 days. Patients with AKI showed higher uNGAL levels than those without AKI from 6 hours to 48 hours. The best accuracy using the cutoff values of 68 ng uNGAL/mg creatinine was achieved at 48 hours when we distinguished patients with and without AKI in all cases. In Group II, we diagnosed AKI in 4 of 9 patients, and cardiac output was significantly higher in patients who developed AKI at 0 hours. Conclusion Both uNGAL and cardiac output determinations allow the prediction of AKI in infected cirrhotic patients earlier than increments in serum creatinine. PMID:26484038

  15. A SCUBA diver with acute kidney injury.

    PubMed

    Gleeson, Patrick James; Kelly, Yvelynne; Ni Sheaghdha, Eadaoin; Lappin, David

    2015-01-01

    An otherwise healthy young man was transferred to our hospital after a diving incident. He had made an uncontrolled ascent from 10 m. On arrival he appeared well. No hypotensive episodes occurred during the transfer. He denied having arthralgias, back pain, dyspnoea or neurological symptoms. Laboratory investigations revealed acutely elevated creatinine (170 µmol/L) and creatine kinase (909 U/L). Radiology was consistent with a focus of pulmonary barotrauma and intrinsic renal disease. Creatine kinase is a marker of arterial gas embolism (AGE). We determined that our patient suffered acute kidney injury as a result of gas embolisation to his renal vasculature from an area of pulmonary barotrauma. Creatinine fell the following day in response to aggressive intravenous fluids. This is the first reported case of acute kidney injury secondary to AGE. Biochemical studies should be part of the routine assessment of patients involved in diving incidents. PMID:25948841

  16. A SCUBA diver with acute kidney injury.

    PubMed

    Gleeson, Patrick James; Kelly, Yvelynne; Ni Sheaghdha, Eadaoin; Lappin, David

    2015-01-01

    An otherwise healthy young man was transferred to our hospital after a diving incident. He had made an uncontrolled ascent from 10 m. On arrival he appeared well. No hypotensive episodes occurred during the transfer. He denied having arthralgias, back pain, dyspnoea or neurological symptoms. Laboratory investigations revealed acutely elevated creatinine (170 µmol/L) and creatine kinase (909 U/L). Radiology was consistent with a focus of pulmonary barotrauma and intrinsic renal disease. Creatine kinase is a marker of arterial gas embolism (AGE). We determined that our patient suffered acute kidney injury as a result of gas embolisation to his renal vasculature from an area of pulmonary barotrauma. Creatinine fell the following day in response to aggressive intravenous fluids. This is the first reported case of acute kidney injury secondary to AGE. Biochemical studies should be part of the routine assessment of patients involved in diving incidents.

  17. Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation.

    PubMed

    Malyszko, Jolanta; Lukaszyk, Ewelina; Glowinska, Irena; Durlik, Magdalena

    2015-01-01

    Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness. PMID:26175216

  18. Difference between pre-operative and cardiopulmonary bypass mean arterial pressure is independently associated with early cardiac surgery-associated acute kidney injury

    PubMed Central

    2010-01-01

    Background Cardiac surgery-associated acute kidney injury (CSA-AKI) contributes to increased morbidity and mortality. However, its pathophysiology remains incompletely understood. We hypothesized that intra-operative mean arterial pressure (MAP) relative to pre-operative MAP would be an important predisposing factor for CSA-AKI. Methods We performed a prospective observational study of 157 consecutive high-risk patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The primary exposure was delta MAP, defined as the pre-operative MAP minus average MAP during CPB. Secondary exposure was CPB flow. The primary outcome was early CSA-AKI, defined by a minimum RIFLE class - RISK. Univariate and multivariate logistic regression were performed to explore for association between delta MAP and CSA-AKI. Results Mean (± SD) age was 65.9 ± 14.7 years, 70.1% were male, 47.8% had isolated coronary bypass graft (CABG) surgery, 24.2% had isolated valve surgery and 16.6% had combined procedures. Mean (± SD) pre-operative, intra-operative and delta MAP were 86.6 ± 13.2, 57.4 ± 5.0 and 29.4 ± 13.5 mmHg, respectively. Sixty-five patients (41%) developed CSA-AKI within in the first 24 hours post surgery. By multivariate logistic regression, a delta MAP≥26 mmHg (odds ratio [OR], 2.8; 95%CI, 1.3-6.1, p = 0.009) and CPB flow rate ≥54 mL/kg/min (OR, 0.2, 0.1-0.5, p < 0.001) were independently associated with CSA-AKI. Additional variables associated with CSA-AKI included use of a side-biting aortic clamp (OR, 3.0; 1.3-7.1, p = 0.012), and body mass index ≥25 (OR, 4.2; 1.6-11.2, p = 0.004). Conclusion A large delta MAP and lower CPB flow during cardiac surgery are independently associated with early post-operative CSA-AKI in high-risk patients. Delta MAP represents a potentially modifiable intra-operative factor for development of CSA-AKI that necessitates further inquiry. PMID:20825657

  19. Acute kidney injury: A rare cause.

    PubMed

    Mendonca, Satish; Barki, Satish; Mishra, Mayank; Kumar, R S V; Gupta, Devika; Gupta, Pooja

    2015-09-01

    We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering. PMID:26354573

  20. Acute Kidney Injury in Pediatric Heart Failure.

    PubMed

    Riley, Alyssa; Gebhard, Daniel J; Akcan-Arikan, Ayse

    2016-01-01

    Acute kidney injury (AKI) is very common in pediatric medical and surgical cardiac patients. Not only is it an independent risk factor for increased morbidity and mortality in the short run, but repeated episodes of AKI lead to chronic kidney disease (CKD) especially in the most vulnerable hosts with multiple risk factors, such as heart transplant recipients. The cardiorenal syndrome, a term coined to emphasize the bidirectional nature of simultaneous or sequential cardiac-renal dysfunction both in acute and chronic settings, has been recently described in adults but scarcely reported in children. Despite the common occurrence and clinical and financial impact, AKI in pediatric heart failure outside of cardiac surgery populations remains poorly studied and there are no large-scale pediatric specific preventive or therapeutic studies to date. This article will review pediatric aspects of the cardiorenal syndrome in terms of pathophysiology, clinical impact and treatment options.

  1. Dengue-associated acute kidney injury

    PubMed Central

    Oliveira, João Fernando Picollo; Burdmann, Emmanuel A.

    2015-01-01

    Dengue is presently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. Acute kidney injury (AKI) is a serious and potentially lethal complication of this disease, and the actual incidence is unknown. In this review, we will assess the most relevant epidemiological and clinical data regarding dengue and the available evidence on the frequency, etiopathogenesis, outcomes and treatment of dengue-associated AKI. PMID:26613023

  2. Acute Kidney Injury: Controversies Revisited

    PubMed Central

    Yong, Kenneth; Dogra, Gursharan; Boudville, Neil; Pinder, Mary; Lim, Wai

    2011-01-01

    This paper addresses the epidemiology of AKI specifically in relation to recent changes in AKI classification and revisits the controversies regarding the timing of initiation of dialysis and the use of peritoneal dialysis as a renal replacement therapy for AKI. In summary, the new RIFLE/AKIN classifications of AKI have facilitated more uniform diagnosis of AKI and clinically significant risk stratification. Regardless, the issue of timing of dialysis initiation still remains unanswered and warrants further examination. Furthermore, peritoneal dialysis as a treatment modality for AKI remains underutilised in spite of potential beneficial effects. Future research should be directed at identifying early reliable biomarkers of AKI, which in conjunction with RIFLE/AKIN classifications of AKI could facilitate well-designed large randomised controlled trials of early versus late initiation of dialysis in AKI. In addition, further studies of peritoneal dialysis in AKI addressing dialysis dose and associated complications are required for this therapy to be accepted more widely by clinicians. PMID:21660314

  3. Acute and Chronic Allograft Dysfunction in Kidney Transplant Recipients.

    PubMed

    Goldberg, Ryan J; Weng, Francis L; Kandula, Praveen

    2016-05-01

    Allograft dysfunction after a kidney transplant is often clinically asymptomatic and is usually detected as an increase in serum creatinine level with corresponding decrease in glomerular filtration rate. The diagnostic evaluation may include blood tests, urinalysis, transplant ultrasonography, radionuclide imaging, and allograft biopsy. Whether it occurs early or later after transplant, allograft dysfunction requires prompt evaluation to determine its cause and subsequent management. Acute rejection, medication toxicity from calcineurin inhibitors, and BK virus nephropathy can occur early or later. Other later causes include transplant glomerulopathy, recurrent glomerulonephritis, and renal artery stenosis.

  4. [Drug-induced acute kidney injury].

    PubMed

    Derungs, Adrian

    2015-12-01

    Due to their physiological function, the kidneys are exposed to high concentrations of numerous drugs and their metabolites, making them vulnerable to drug-related injuries. This article provides an overview of the pathophysiological mechanisms involved in nephrotoxicity, the most common nephrotoxic drugs, and the risk factors for the occurrence of drug-induced acute kidney injuries. NSAIDs, diuretics, ACE inhibitors, and angiotensin II receptor blockers (ARBs} are the most frequent prerenal causes of an acute elevation in creatinine levels. Primary vascular damage arises from thrombotic microangiopathy (e. g. due to cic/osporin, tacrolimus, muromonab-CD3, mitomycin C, quinine, ticlopidine, clopidogrel}. Anticoagulants and thrombolytic medications lead to secondary blood vessel damage by cholesterol emboli, embolism of thrombus material into the periphery or bleeding. Tubulopathies can be observed on treatment with ifosfamide and cisplatin (rarely with cyclophosphamide or carboplatin), aminoglycosides, vancomycin, and radiocontrast agents. Immunological mechanisms underlie interstitial nephritides, which are induced by drugs in about 85% of cases. In drug-induced glomerulopathies;- renal biopsy allows closer identification of the triggering medication. Drug-induced systemic lupus erythematosus (SLE} represents a special form of immune complex glomerulonephritis and can be triggered by procainamide, hydralazine, isoniazid, methyldopa, quinidine, chlorpromazine, and propylthiouracil. Crystal-induced kidney injury is caused by precipitation of drugs (e. g. aciclovir, sulfonamide antibiotics, methotrexate, indinavir) in the renal tubules and the urine-conducting organs with consecutive obstruction thereof. PMID:26654816

  5. Acute kidney injury in acute on chronic liver failure.

    PubMed

    Maiwall, Rakhi; Sarin, S K; Moreau, Richard

    2016-03-01

    Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.

  6. Does orlistat cause acute kidney injury?

    PubMed

    Beyea, Michael M; Garg, Amit X; Weir, Matthew A

    2012-04-01

    Orlistat is an inhibitor of gastric and pancreatic lipase with proven efficacy in the augmentation and maintenance of weight loss. Although its use has been limited by troublesome but benign gastrointestinal side effects, it has more recently been associated with acute kidney injury (AKI). In this review, we summarize orlistat's benefits and drawbacks and discuss the body of evidence supporting its role as a cause of AKI. Although we cannot yet draw an unequivocal causal link between orlistat and AKI, there is enough evidence to include orlistat exposure in the clinical assessment of patients with AKI. PMID:25083225

  7. Contrast-Induced Acute Kidney Injury.

    PubMed

    McCullough, Peter A; Choi, James P; Feghali, Georges A; Schussler, Jeffrey M; Stoler, Robert M; Vallabahn, Ravi C; Mehta, Ankit

    2016-09-27

    Coronary angiography and percutaneous intervention rely on the use of iodinated intravascular contrast for vessel and chamber imaging. Despite advancements in imaging and interventional techniques, iodinated contrast continues to pose a risk of contrast-induced acute kidney injury (CI-AKI) for a subgroup of patients at risk for this complication. There has been a consistent and graded signal of risk for associated outcomes including need for renal replacement therapy, rehospitalization, and death, according to the incidence and severity of CI-AKI. This paper reviews the epidemiology, pathophysiology, prognosis, and management of CI-AKI as it applies to the cardiac catheterization laboratory. PMID:27659469

  8. Does orlistat cause acute kidney injury?

    PubMed Central

    Beyea, Michael M.; Garg, Amit X.

    2012-01-01

    Orlistat is an inhibitor of gastric and pancreatic lipase with proven efficacy in the augmentation and maintenance of weight loss. Although its use has been limited by troublesome but benign gastrointestinal side effects, it has more recently been associated with acute kidney injury (AKI). In this review, we summarize orlistat’s benefits and drawbacks and discuss the body of evidence supporting its role as a cause of AKI. Although we cannot yet draw an unequivocal causal link between orlistat and AKI, there is enough evidence to include orlistat exposure in the clinical assessment of patients with AKI. PMID:25083225

  9. Comparison of serum creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin for acute kidney injury occurrence according to risk, injury, failure, loss, and end-stage criteria classification system in early after living kidney donation.

    PubMed

    Hekmat, Reza; Mohebi, Mahmood

    2016-01-01

    To evaluate the kidney function after living kidney donation, we measured serum creatinine (SCr), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) of 42 living donors before uninephrectomy and in three immediate days after it. We also evaluated the prevalence of the occurrence of the different stages of acute kidney injury (AKI) classified according to risk, injury, failure, loss, and end-stage (RIFLE) criteria, and accuracy of each of these three biomarkers for predicting them were evaluated. Significant serum NGAL (s-NGAL) changes were limited to the 1 st day after donation, whereas SCr and cystatin C changes continued to the third day after donation. s-NGAL level in the 1 st day and serum cystatin C in the 3 rd day after donation, respectively, had the largest area under curve and best sensitivity and specificity for Stage 1 (risk) AKI prediction. During the immediate three days after donation, about half of patients suffered from AKI; mostly Stage 1 (injury). The sequence of the emergence of s-NGAL and s-cystatin C in the 1 st and 3 rd days as biomarkers with highest accuracy and power for RIFLE criteria defined AKI stage discrimination in our study was comparable to previous studies. We conclude that our study suggests that AKI was best detected in the 1 st day after uninephrectomy by the s-NGAL levels, whereas cystatin C was the best in the 3 rd day after donation for detection of AKI. PMID:27424680

  10. 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.

  11. Programmed necrosis in acute kidney injury.

    PubMed

    Linkermann, Andreas; De Zen, Federica; Weinberg, Joel; Kunzendorf, Ulrich; Krautwald, Stefan

    2012-09-01

    Programmed cell death (PCD) had been widely used synonymously to caspase-mediated apoptosis until caspase-independent cell death was described. Identification of necrosis as a regulated process in ischaemic conditions has recently changed our understanding of PCD. At least three pathways of programmed necrosis (PN) have been identified. First, receptor-interacting protein kinase 3 (RIP3)-dependent necroptosis causes organ failure following stroke, myocardial infarction and renal ischaemia/reperfusion injury. Necroptosis can be mediated either by a large intracellular caspase-8-containing signalling complex called the ripoptosome or by the RIP1-/RIP3-containing necroptosome and is controlled by a caspase-8/FLICE inhibitory protein(long) heterodimer at least in the latter case. Second, mitochondrial permeability transition mediates apoptotic or necrotic stimuli and depends on the mitochondrial protein cyclophilin D. The third PN pathway involves the poly(ADP-ribose) polymerase-calpain axis that contributes to acute kidney injury (AKI). Preclinical interference with the PN pathways therefore raises expectations for the future treatment of ischaemic conditions. In this brief review, we aim to summarize the clinically relevant PCD pathways and to transfer the basic science data to settings of AKI. We conclude that pathologists were quite right to refer to ischaemic kidney injury as 'acute tubular necrosis'. PMID:22942173

  12. Laboratory Test Surveillance following Acute Kidney Injury

    PubMed Central

    Matheny, Michael E.; Peterson, Josh F.; Eden, Svetlana K.; Hung, Adriana M.; Speroff, Theodore; Abdel-Kader, Khaled; Parr, Sharidan K.; Ikizler, T. Alp; Siew, Edward D.

    2014-01-01

    Background Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. Methods We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥60 L/min/1.73 m2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients. Results A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. Conclusions Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease. PMID:25117447

  13. The role of the complement system in acute kidney injury.

    PubMed

    McCullough, James W; Renner, Brandon; Thurman, Joshua M

    2013-11-01

    Acute kidney injury is a common and severe clinical problem. Patients who develop acute kidney injury are at increased risk of death despite supportive measures such as hemodialysis. Research in recent years has shown that tissue inflammation is central to the pathogenesis of renal injury, even after nonimmune insults such as ischemia/reperfusion and toxins. Examination of clinical samples and preclinical models has shown that activation of the complement system is a critical cause of acute kidney injury. Furthermore, complement activation within the injured kidney is a proximal trigger of many downstream inflammatory events within the renal parenchyma that exacerbate injury to the kidney. Complement activation also may account for the systemic inflammatory events that contribute to remote organ injury and patient mortality. Complement inhibitory drugs have now entered clinical use and may provide an important new therapeutic approach for patients suffering from, or at high risk of developing, acute kidney injury.

  14. KIM-1-mediated phagocytosis reduces acute injury to the kidney.

    PubMed

    Yang, Li; Brooks, Craig R; Xiao, Sheng; Sabbisetti, Venkata; Yeung, Melissa Y; Hsiao, Li-Li; Ichimura, Takaharu; Kuchroo, Vijay; Bonventre, Joseph V

    2015-04-01

    Kidney injury molecule 1 (KIM-1, also known as TIM-1) is markedly upregulated in the proximal tubule after injury and is maladaptive when chronically expressed. Here, we determined that early in the injury process, however, KIM-1 expression is antiinflammatory due to its mediation of phagocytic processes in tubule cells. Using various models of acute kidney injury (AKI) and mice expressing mutant forms of KIM-1, we demonstrated a mucin domain-dependent protective effect of epithelial KIM-1 expression that involves downregulation of innate immunity. Deletion of the mucin domain markedly impaired KIM-1-mediated phagocytic function, resulting in increased proinflammatory cytokine production, decreased antiinflammatory growth factor secretion by proximal epithelial cells, and a subsequent increase in tissue macrophages. Mice expressing KIM-1Δmucin had greater functional impairment, inflammatory responses, and mortality in response to ischemia- and cisplatin-induced AKI. Compared with primary renal proximal tubule cells isolated from KIM-1Δmucin mice, those from WT mice had reduced proinflammatory cytokine secretion and impaired macrophage activation. The antiinflammatory effect of KIM-1 expression was due to the interaction of KIM-1 with p85 and subsequent PI3K-dependent downmodulation of NF-κB. Hence, KIM-1-mediated epithelial cell phagocytosis of apoptotic cells protects the kidney after acute injury by downregulating innate immunity and inflammation.

  15. Acute kidney injury in pregnancy-current status.

    PubMed

    Acharya, Anjali; Santos, Jolina; Linde, Brian; Anis, Kisra

    2013-05-01

    Pregnancy-related acute kidney injury (PR-AKI) causes significant maternal and fetal morbidity and mortality. Management of PR-AKI warrants a thorough understanding of the physiologic adaptations in the kidney and the urinary tract. Categorization of etiologies of PR-AKI is similar to that of acute kidney injury (AKI) in the nonpregnant population. The causes differ between developed and developing countries, with thrombotic microangiopathies (TMAs) being common in the former and septic abortion and puerperal sepsis in the latter. The incidence of PR-AKI is reported to be on a decline, but there is no consensus on the exact definition of the condition. The physiologic changes in pregnancy make diagnosis of PR-AKI difficult. Newer biomarkers are being studied extensively but are not yet available for clinical use. Early and accurate diagnosis is necessary to improve maternal and fetal outcomes. Timely identification of "at-risk" individuals and treatment of underlying conditions such as sepsis, preeclampsia, and TMAs remain the cornerstone of management. Questions regarding renal replacement therapy such as modality, optimal prescription, and timing of initiation in PR-AKI remain unclear. There is a need to systematically explore these variables to improve care of women with PR-AKI. PMID:23928385

  16. Analyses of acute kidney injury biomarkers by ultra-high performance liquid chromatography with mass spectrometry.

    PubMed

    Al Za'abi, Mohammed; Ali, Badreldin H; ALOthman, Zeid A; Ali, Imran

    2016-01-01

    The newly developed acute kidney injury biomarkers are very important for the early and timely detection of kidney diseases. This review contains details of the analyses of several acute kidney injury biomarkers using ultra-high performance liquid chromatography-mass spectrometry in urine and plasma samples. In this review we attempt to discuss some aspects of the types of the biomarkers, patents, sample preparation, and the analyses. Besides, efforts were also made to discuss the possible uses of superficially porous (core-shell) columns in traditional and inexpensive high-performance liquid chromatography instruments. Additionally, the challenges and the future prospects are also highlighted. The present review will be useful for the academicians, scientists, and clinicians for the early detection of acute kidney injury biomarkers.

  17. A case of acute kidney injury by near-drowning.

    PubMed

    Amir, A; Lee, Y L

    2013-01-01

    Acute kidney injury following immersion or near-drowning is rarely described and no data from Malaysia have been found. We report a case of acute kidney injury following a near-drowning event. A 20-year-old man who recovered from near-drowning in a swimming pool 5 days earlier presented to our clinic with abdominal pain, anorexia, nausea and polyuria. Dipstick urinalysis showed a trace of blood. The serum creatinine level was 10-fold higher than the normal range. A bedside ultrasound showed features suggestive of acute tubular necrosis. He is then referred to the hospital with the diagnosis of acute kidney injury with the possibility of acute tubular necrosis secondary to near-drowning. We suggest that any patient presenting after immersion or near-drowning to be should assessed for potential acute kidney injury.

  18. Molecular determinants of acute kidney injury

    PubMed Central

    Husi, Holger; Human, Christin

    2015-01-01

    Abstract: Background: Acute kidney injury (AKI) is a condition that leads to a rapid deterioration of renal function associated with impairment to maintain electrolyte and acid balance, and, if left untreated, ultimately irreversible kidney damage and renal necrosis. There are a number of causes that can trigger AKI, ranging from underlying conditions as well as trauma and surgery. Specifically, the global rise in surgical procedures led to a substantial increase of AKI incidence rates, which in turn impacts on mortality rates, quality of life and economic costs to the healthcare system. However, no effective therapy for AKI exists. Current approaches, such as pharmacological intervention, help in alleviating symptoms in slowing down the progression, but do not prevent or reverse AKI-induced organ damage. Methods: An in-depth understanding of the molecular machinery involved in and modulated by AKI induction and progression is necessary to specifically pharmacologically target key molecules. A major hurdle to devise a successful strategy is the multifactorial and complex nature of the disorder itself, whereby the activation of a number of seemingly independent molecular pathways in the kidney leads to apoptotic and necrotic events. Results: The renin-angiotensin-aldosterone-system (RAAS) axis appears to be a common element, leading to downstream events such as triggers of immune responses via the NFB pathway. Other pathways intricately linked with AKI-induction and progression are the tumor necrosis factor alpha (TNF α) and transforming growth factor beta (TGF β) signaling cascades, as well as a number of other modulators. Surprisingly, it has been shown that the involvement of the glutamatergic axis, believed to be mainly a component of the neurological system, is also a major contributor. Conclusions: Here we address the current understanding of the molecular pathways evoked in AKI, their interplay, and the potential to pharmacologically intervene in the

  19. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  20. Reflex anuria: a rare cause of acute kidney injury

    PubMed Central

    Adediran, Samuel; Dhakarwal, Pradeep

    2014-01-01

    Background Acute Kidney Injury results from pre renal, post renal or intrinsic renal causes. Reflex anuria is a very rare cause of renal impairment which happens due to irritation or trauma to one kidney or ureter, or severely painful stimuli to other nearby organs. Case Presentation Here we present a case of acute kidney injury secondary to reflex anuria in a patient who underwent extensive gynecological surgery along with ureteral manipulation which recovered spontaneously. Conclusion Reflex Anuria is a rare and often not considered as cause of acute kidney injury. This case illustrates that this should be kept as a differential in potential cause of acute kidney injury in patient undergoing urogenital or gynecological surgeries. PMID:24765255

  1. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    PubMed

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. PMID:26319781

  2. Acute kidney injury in the tropics

    PubMed Central

    Mathew, Ashish Jacob; George, Jacob

    2011-01-01

    Acute kidney injury (AKI) is one of the most challenging problems faced by clinicians in the tropics owing to its fast-changing burden. AKI in the tropics is strikingly different from that in the developed world in terms of etiology and presentation. In addition, there is a stark contrast between well-developed and poor areas in the tropics. The true epidemiological picture of AKI in the tropics is not well understood due to the late presentation of patients to tertiary centers. Infections remain the major culprit in most cases of AKI, with high mortality rates in the tropics. Human immunodeficiency virus–related AKI, related to nephrotoxicity due to antiretroviral therapy, is on the rise. Acute tubular necrosis and thrombotic microangiopathy are the most common mechanisms of AKI. A notable problem in the tropics is the scarcity of resources in health centers to support patients who require critical care due to AKI. This article reviews the unique and contrasting nature of AKI in the tropics and describes its management in each situation. PMID:21911980

  3. Acute Renal Failure - A Serious Complication in Patients After Kidney Transplantation.

    PubMed

    Basta-Jovanovic, G; Bogdanovic, Lj; Radunovic, M; Prostran, M; Naumovic, R; Simic-Ogrizovic, S; Radojevic-Skodric, S

    2016-01-01

    Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails. Along the entire transplantation time course, there is a great demand for novel immune and nonimmune injury biomarkers. The use of these markers can be of great help in the monitoring of kidney injury in potential kidney donors, where acute kidney damage can be overlooked, in predicting acute transplant dysfunction during the early post-transplant periods, or in predicting chronic changes in long term followup. Numerous investigations have demonstrated that biomarkers that have the highest predictive value in acute kidney injury include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that the ideal biomarker to fulfill all the needs in renal transplant has not been identified yet. Although, in many animal models, new biomarkers are emerging for predicting acute and chronic allograft damage, in human allograft analysis they are still not routinely accepted and renal biopsy still remains the gold standard. PMID:27498898

  4. Acute kidney injury by arsine poisoning: the ultrastructural pathology of the kidney.

    PubMed

    Lee, Jun Young; Eom, Minseob; Yang, Jae Won; Han, Byoung Geun; Choi, Seung Ok; Kim, Jae Seok

    2013-01-01

    Arsenic is a terribly poisonous material. There have been many reports of arsine poisoning in workers, and a few have discussed acute kidney injury by arsine. But literatures which investigated the pathologic findings are uncommon, and especially, the ones describing ultrastructural findings are rare. Here, we report an incident of acute arsine poisoning complicated by acute kidney injury and suggest the characteristics of the renal pathology in arsine-induced renal injury, especially the ultrastructural findings.

  5. MicroRNAs in acute kidney injury.

    PubMed

    Fan, Pei-Chun; Chen, Chia-Chun; Chen, Yung-Chang; Chang, Yu-Sun; Chu, Pao-Hsien

    2016-01-01

    Acute kidney injury (AKI) is an important clinical issue that is associated with significant morbidity and mortality. Despite research advances over the past decades, the complex pathophysiology of AKI is not fully understood. The regulatory mechanisms underlying post-AKI repair and fibrosis have not been clarified either. Furthermore, there is no definitively effective treatment for AKI. MicroRNAs (miRNAs) are endogenous single-stranded noncoding RNAs of 19~23 nucleotides that have been shown to be crucial to the post-transcriptional regulation of various cellular biological functions, including proliferation, differentiation, metabolism, and apoptosis. In addition to being fundamental to normal development and physiology, miRNAs also play important roles in various human diseases. In AKI, some miRNAs appear to act pathogenically by promoting inflammation, apoptosis, and fibrosis, while others may act protectively by exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenic effects. Thus, miRNAs have not only emerged as novel biomarkers for AKI; they also hold promise to be potential therapeutic targets. PMID:27608623

  6. Challenges of targeting vascular stability in acute kidney injury.

    PubMed

    Basile, David P

    2008-08-01

    Acute kidney injury following folate administration is characterized by a vascular remodeling that is initially proliferative but subsequently results in vascular endothelial loss. Interventions directed toward promoting endothelial growth may preserve vascular structure and therefore renal function. However, angiopoietin-1 therapy in the setting of folate-induced acute kidney injury resulted in an expanded fibrotic response despite apparent preservation of the vasculature, indicating that renal repair responses are complex and vascular-directed therapies should be approached with caution.

  7. Keep Your Kidneys Healthy: Catch Kidney Disease Early

    MedlinePlus

    ... point, you may need a kidney transplant or dialysis. It’s a good idea to talk with your ... healthy kidneys and finding a well-matched donor. Dialysis is a treatment that filters wastes and water ...

  8. Clinical trial endpoints in acute kidney injury.

    PubMed

    Billings, Frederic T; Shaw, Andrew D

    2014-01-01

    The development and use of consensus criteria for acute kidney injury (AKI) diagnosis and the inclusion of recently identified markers of renal parenchymal damage as endpoints in clinical trials have improved the ability of physicians to compare the incidence and severity of AKI across patient populations, provided targets for testing new treatments, and may increase insight into the mechanisms of AKI. To date, these markers have not consistently translated into important clinical outcomes. Is that because these markers of renal injury/dysfunction are measurements of process of care (and not indicative of persistently impaired renal function), or is it because patients do actually recover from AKI? Physicians currently have limited ability to measure renal function reserve, and the ultimate consequence of a case of AKI on long-term morbidity remains unclear. There is little doubt that groups of patients who develop AKI have worse outcomes than groups of patients who do not, but investigators are now realizing the value of measuring clinically meaningful renal endpoints in all subjects enrolled in AKI clinical trials. Important examples of these outcomes include persistently impaired renal function, new hemodialysis, and death. We propose that these major adverse kidney events (MAKE) be included in all effectiveness clinical trials. Adaptation of the MAKE composite assessed 30, 60, or 90 days following AKI (i.e., MAKE30 or MAKE90) will improve our capacity to understand and treat AKI and may also provide a consensus composite to allow comparison of different interventions. Primary endpoints for phase I and II clinical trials, on the other hand, should continue to use continuous markers of renal injury/dysfunction as well as 'hard' clinical outcomes in order to generate meaningful data with limited subject exposure to untested treatments. By doing so, investigators may assess safety without requiring large sample sizes, demonstrate treatment effect of an unknown

  9. Severe acute kidney injury as presentation of Burkitt's lymphoma.

    PubMed

    ter Haar, Eva; Labarque, Veerle; Tousseyn, Thomas; Mekahli, Djalila

    2016-01-01

    We discuss a case of acute kidney injury (AKI) at a very young age caused by primary lymphomatous renal infiltration due to Burkitt's lymphoma and analyse the literature on this rare condition. At presentation, clinical examination showed impressive bilateral nephromegaly and hypertension. Blood analysis indicated severe AKI, mild anaemia and normal serum electrolytes. There were no signs of tumour lysis syndrome. Urine sediment was normal, with neither haematuria nor proteinuria. Abdominal ultrasound demonstrated bilateral renal enlargement (+12 SD), with increased corticomedullar differentiation. MRI demonstrated the presence of a homogenous renal enlargement with features of an infiltrative lesion. Ultimately, microscopic and immunohistochemical analysis of the renal biopsy confirmed the diagnosis of Burkitt's lymphoma. Early and aggressive therapy is the key to ensure a good outcome. PMID:27118748

  10. Synthetic marijuana and acute kidney injury: an unforeseen association

    PubMed Central

    Kazory, Amir; Aiyer, Ravi

    2013-01-01

    Synthetic cannabinoids (SCs) have emerged as drugs of abuse with increasing popularity among young adults. The potential renal complication related to the abuse of SC was not recognized until recently. Here, we present a case of severe acute kidney injury (AKI) that developed after inhalation of SC in an otherwise healthy young patient. A kidney biopsy revealed severe acute tubular necrosis, and supportive management resulted in the recovery of the kidney function. Herein, we briefly summarize the only two previous reports (a total of 21 cases) on the association between SC abuse and renal dysfunction and identify the common aspects in all observations. PMID:26064495

  11. Recent advances in the understanding of acute kidney injury

    PubMed Central

    Tögel, Florian

    2014-01-01

    Acute kidney injury (AKI) is a common clinical entity associated with high morbidity and mortality and clinical costs. The pathophysiology is multifaceted and involves inflammation, tubular injury, and vascular damage. Recently identified components include necroptosis, a special form of cell death, and autophagy. Most of the pathophysiological knowledge is obtained from animal models but these do not directly reflect the reality of the clinical situation. Tubular cells have a remarkable capacity to regenerate, and the role of stem/progenitor cells is discussed. Acute kidney injury is frequently associated with chronic kidney disease, and the implications are widespread. PMID:25343040

  12. Early management of acute pancreatitis.

    PubMed

    Schepers, Nicolien J; Besselink, Marc G H; van Santvoort, Hjalmar C; Bakker, Olaf J; Bruno, Marco J

    2013-10-01

    Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.

  13. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide

    PubMed Central

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  14. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide.

    PubMed

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  15. Early seizures in acute stroke

    PubMed Central

    Mohamed, Chraa; Kissani, Najib

    2015-01-01

    Early seizures (ES) may complicate the clinical course of patients with acute stroke. The aim of this study was to assess the frequency and the predictive factors for early seizures as well the clinical outcome in patients with first-ever stroke. A total of 352 consecutive patients with first-ever stroke, admitted to our department, were included in this retrospective study. Early seizures were defined as seizures occurring within 7 days from acute stroke. Patients with history of epilepsy were excluded. About 47 patients (13%) had early seizure, and 8 had a status epilepticus. We had 28 women and 19 men. The mean age was 71.6 ± 14.6. They were significantly more common in patients with cortical involvement, severe and large stroke, and in patient with cortical associated hemorrhage. ES were associated with an increase in adverse outcome (mortality and disability). Early seizures occured in about 13% of patients with acute stroke. In these patients hemorrhagic transformation is a predictive factor for ES. ES seem to be associated with a worse outcome after acute stroke. PMID:26097640

  16. Molecular mediators of favism-induced acute kidney injury.

    PubMed

    García-Camín, Rosa María; Goma, Montserrat; Osuna, Rosa García; Rubio-Navarro, Alfonso; Buendía, Irene; Ortiz, Alberto; Egido, Jesús; Manzarbeitia, Félix; Chevarria, Julio Leonel; Gluksmann, María Constanza; Moreno, Juan Antonio

    2014-03-01

    Intolerance to fava beans in subjects with glucose-6-phosphate-dehydrogenase deficiency (favism) may lead to severe hemolytic crises and decreased renal function. Renal biopsy findings exploring the molecular mechanisms of renal damage in favism have not been previously reported. We report a case of favism-associated acute kidney injury in which renal biopsy showed acute tubular necrosis and massive iron deposits in tubular cells. Interestingly, iron deposit areas were characterized by the presence of oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) and macrophages expressing the hemoglobin scavenger receptor CD163. In addition, iron deposits, NADPH-p22 phox, hemeoxigenase- 1 and CD163 positive cells were observed in some glomeruli. These results identify both glomerular and tubular involvement in favism-associated acute kidney injury and suggest novel therapeutic targets to prevent or accelerate recovery from acute kidney injury.

  17. Molecular mediators of favism-induced acute kidney injury.

    PubMed

    García-Camín, Rosa María; Goma, Montserrat; Osuna, Rosa García; Rubio-Navarro, Alfonso; Buendía, Irene; Ortiz, Alberto; Egido, Jesús; Manzarbeitia, Félix; Chevarria, Julio Leonel; Gluksmann, María Constanza; Moreno, Juan Antonio

    2014-03-01

    Intolerance to fava beans in subjects with glucose-6-phosphate-dehydrogenase deficiency (favism) may lead to severe hemolytic crises and decreased renal function. Renal biopsy findings exploring the molecular mechanisms of renal damage in favism have not been previously reported. We report a case of favism-associated acute kidney injury in which renal biopsy showed acute tubular necrosis and massive iron deposits in tubular cells. Interestingly, iron deposit areas were characterized by the presence of oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) and macrophages expressing the hemoglobin scavenger receptor CD163. In addition, iron deposits, NADPH-p22 phox, hemeoxigenase- 1 and CD163 positive cells were observed in some glomeruli. These results identify both glomerular and tubular involvement in favism-associated acute kidney injury and suggest novel therapeutic targets to prevent or accelerate recovery from acute kidney injury. PMID:23006341

  18. Electronic Medical Record-Based Predictive Model for Acute Kidney Injury in an Acute Care Hospital.

    PubMed

    Laszczyńska, Olga; Severo, Milton; Azevedo, Ana

    2016-01-01

    Patients with acute kidney injury (AKI) are at risk for increased morbidity and mortality. Lack of specific treatment has meant that efforts have focused on early diagnosis and timely treatment. Advanced algorithms for clinical assistance including AKI prediction models have potential to provide accurate risk estimates. In this project, we aim to provide a clinical decision supporting system (CDSS) based on a self-learning predictive model for AKI in patients of an acute care hospital. Data of all in-patient episodes in adults admitted will be analysed using "data mining" techniques to build a prediction model. The subsequent machine-learning process including two algorithms for data stream and concept drift will refine the predictive ability of the model. Simulation studies on the model will be used to quantify the expected impact of several scenarios of change in factors that influence AKI incidence. The proposed dynamic CDSS will apply to future in-hospital AKI surveillance in clinical practice. PMID:27577501

  19. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status

    PubMed Central

    Zhou, Hai Ying; Chen, Tian Wu; Zhang, Xiao Ming

    2016-01-01

    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Many established approaches are not applicable to humans because of their invasiveness. Functional renal magnetic resonance (MR) imaging offers an alternative assessment tool that could be used to evaluate renal morphology and function noninvasively and simultaneously. Thus, the purpose of this review is to illustrate the principle, application, and role of the techniques of functional renal MR imaging, including blood oxygen level-dependent imaging, arterial spin labeling, and diffusion-weighted MR imaging, in the management of AKI. The use of gadolinium in MR imaging may exacerbate renal impairment and cause nephrogenic systemic fibrosis. Therefore, dynamic contrast-enhanced MR imaging will not be discussed in this paper. PMID:26925411

  20. Severe but reversible acute kidney injury resulting from Amanita punctata poisoning

    PubMed Central

    Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee

    2015-01-01

    Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury. PMID:26779427

  1. [Acute conditions after kidney transplantation in patients with autosomal dominant polycystic kidney disease].

    PubMed

    Bujdák, P; Pribylincová, V; Reznícek, J; Miklosi, M; Breza, J

    2003-05-01

    There is a high risk of severe complications after kidney transplantation. In patients with autosomal dominant polycystic kidney disease (AD-PKD) the incidence of complications like ischaemic cardiac disease, acute myocardial infarction, pulmonary embolism, perforation of colonic diverticulosis is especially higher. The authors want to indicate another specific complication, rupture of the cyst of own polycystic kidney with retroperitoneal haemorrhage. Within the group of 658 patients who underwent kidney transplantation between January 1981 and January 2000 there were 54 (8.2%) patients with AD-PKD. Four patients with severe retroperitoneal haemorrhage due to rupture of the cyst of own polycystic kidney we present in a short case reports. All cases were fatal. Expect morphologic and functional follow up of the graft it is necessary to follow up polycystic kidney and indicate urgent nephrectomy in the case of any change.

  2. Suramin protects from cisplatin-induced acute kidney injury.

    PubMed

    Dupre, Tess V; Doll, Mark A; Shah, Parag P; Sharp, Cierra N; Kiefer, Alex; Scherzer, Michael T; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G; Beverly, Levi J; Siskind, Leah J

    2016-02-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer.

  3. Intrarenal Doppler ultrasound studies in normal and acutely obstructed kidneys.

    PubMed

    Rodgers, P M; Bates, J A; Irving, H C

    1992-03-01

    Renal ultrasound examinations and intrarenal arterial Doppler studies were performed on 48 patients with normal renal tracts and 20 patients presenting with acute renal colic resulting from ureteric calculus, 14 of whom had urographic evidence of renal obstruction. The mean resistance index (RI) of the Doppler waveforms obtained on the 14 obstructed kidneys (70.4 +/- 6.22) was significantly higher than the mean RI of the 96 normal kidneys (62.4 +/- 6.43). The mean difference between the RIs of the obstructed kidneys and their contralateral non-obstructed kidneys (8.37 +/- 4.43) was also significantly higher than the differences in RI seen between pairs of normal kidneys (2.70 +/- 1.71). Five out of 14 obstructed kidneys showed no pelvicalyceal dilatation and could not have been shown to be obstructed on conventional sonography. Four of these five had RI changes suggestive of obstruction and thus 13 of 14 obstructed kidneys would have been identified as obstructed by a combination of Doppler and conventional sonographic findings. 10 of the 14 obstructed kidneys were re-examined after passage of a urinary calculus and nine showed a reduction in the RI of the previously obstructed kidneys. The 10th subsequently required ureterolithotomy.

  4. Autophagy is activated to protect against endotoxic acute kidney injury

    PubMed Central

    Mei, Shuqin; Livingston, Man; Hao, Jielu; li, Lin; Mei, Changlin; Dong, Zheng

    2016-01-01

    Endotoxemia in sepsis, characterized by systemic inflammation, is a major cause of acute kidney injury (AKI) in hospitalized patients, especially in intensive care unit; however the underlying pathogenesis is poorly understood. Autophagy is a conserved, cellular catabolic pathway that plays crucial roles in cellular homeostasis including the maintenance of cellular function and viability. The regulation and role of autophagy in septic or endotoxic AKI remains unclear. Here we show that autophagy was induced in kidney tubular cells in mice by the endotoxin lipopolysaccharide (LPS). Pharmacological inhibition of autophagy with chloroquine enhanced LPS-induced AKI. Moreover, specific ablation of autophagy gene 7 (Atg7) from kidney proximal tubules worsened LPS-induced AKI. Together, the results demonstrate convincing evidence of autophagy activation in endotoxic kidney injury and support a renoprotective role of autophagy in kidney tubules. PMID:26916346

  5. Early demographic and clinical predictors of developing acute kidney injury in snake bite patients: A retrospective controlled study from an Indian tertiary care hospital in North Eastern Uttar Pradesh India

    PubMed Central

    Singh, R. R.; Uraiya, Dharmendra; Kumar, Anoop; Tripathi, Neeraj

    2016-01-01

    Aims: This study was conducted retrospectively to define early demographic and clinical predictors for acute kidney injury (AKI) among snake bite patients at the time of hospital admission. Materials and Methods: We analyzed 138 cases with a poisonous snake bite. Patients were classified into two groups according to the presence and absence of AKI. The data regarding clinical features and demographic profile of these patients were collected from the hospital records in a prestructured pro forma and statistically compared. Results: Of the 138 patients of venomous snake bite, 62 developed AKI (44.92%). Patients who developed AKI were older in age. Moreover, prolonged bite to anti-snake venom (ASV) time had a significant relationship in developing AKI (P < 0.05). Among the clinical features, there was an independent positive association of AKI with abdomen pain, tenderness and vomiting, cellulitis, bleeding tendencies, myalgia, and black or brown urine (P < 0.05). Neurological features were inversely associated with renal involvement. Conclusion: We found that marked abdominal pain, tenderness and vomiting, myalgia, black or brown urine, bite site cellulitis, bleeding tendencies, and prolonged (>2 h) bite to ASV time were significantly associated with the development of AKI in snake bite patients. PMID:27555694

  6. Acute kidney injury in dengue fever using Acute Kidney Injury Network criteria: incidence and risk factors.

    PubMed

    Mehra, Nikita; Patel, Amish; Abraham, Georgi; Reddy, Yogesh N V; Reddy, Yuvaram N V

    2012-07-01

    The aim of this study was to assess incidence and risk factors for acute kidney injury (AKI) in patients with dengue fever (DF). A total of 223 patients (males, 130; females, 93; mean age, 26.2 ± 18.2 years) from a tertiary care centre in southern India were retrospectively analysed. Acute renal failure (ARF) developed in 24 (10.8%) patients. Based on the Acute Kidney Injury Network (AKIN) criteria, the results revealed that: 12 (5.4%) had mild AKI; seven (3.1%) had moderate AKI; and five (2.2%) had severe AKI. A further 54 (24%) were diagnosed with dengue haemorrhagic fever (DHF); 11 (5%) were co-infected with leptospirosis; thrombocytopenia was present in 157 (70%); and 64 (29%) were hypotensive. Patients were divided into either group A (with AKI) or group B (without AKI), and group A was divided into mild (A1), moderate (A2) and severe (A3) subgroups. We recorded: a higher total white count (A = 9824; B = 6706; P = 0.01); serum glutamic pyruvic transaminase (SGPT; A = 450; B = 144; P = 0.001); alkaline phosphatase (ALP) levels (A = 207; B = 42; P = 0.001); lower albumin (A = 2.65; B = 3.09; P < 0.001); and serum bicarbonate (A = 20.57; B = 23.21; P = 0.009). Hypotension (P = 0.01), coexisting viral hepatitis (P < 0.001), sepsis (P < 0.001), multiple organ dysfunction syndrome (MODS; P < 0.001) and the need for inotropes (P < 0.001) were associated with DF. Total white count (P = 0.038), glomerular filtration rate (GFR) on discharge (P = 0.034), specific gravity of urine (P = 0.006), ALP (P = 0.013), SGPT (P = 0.042), MODS (P = 0.05) and use of platelet fresh frozen plasma (FFP; P = 0.007) were significantly different between mild, moderate and severe AKI subgroups. Twenty-two (9%) died. AKI is associated with an increased mortality in DF (P = 0.005).

  7. Acute Page kidney immediately following blunt trauma to a solitary pediatric kidney

    PubMed Central

    Tuong, Nicole; Daugherty, Michael; Riddell, Jonathan

    2016-01-01

    Page kidney refers to the occurrence of hypertension secondary to renal compression and is usually associated with a subcapsular or perinephric hematoma. It generally occurs weeks to months after the initial injury. We report on a case of Page kidney occurring acutely after Grade IV blunt renal trauma in a pediatric patient with a solitary kidney following a tobogganing accident. The child was initially managed conservatively and discharged after six days bed-rest. He re-presented post-injury Day 12 with recurrent hematuria, anemia, hypertension, and renal failure that required eventual, and successful, surgical exploration.

  8. Acute kidney injury in sepsis: transient or intrinsic?

    PubMed

    Jörres, Achim

    2013-11-20

    The negative prediction of intrinsic versus transient acute kidney injury (AKI) in septic patients may be facilitated by combined assessment of fractional excretion of sodium and urea. If both excretions are high this would signal the presence of transient AKI and suggest that successful restoration of diuresis by conservative therapy is likely, thus supporting a wait-and-watch approach regarding the initiation of acute renal replacement therapy.

  9. Histone lysine crotonylation during acute kidney injury in mice

    PubMed Central

    Ruiz-Andres, Olga; Sanchez-Niño, Maria Dolores; Cannata-Ortiz, Pablo; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belen

    2016-01-01

    ABSTRACT Acute kidney injury (AKI) is a potentially lethal condition for which no therapy is available beyond replacement of renal function. Post-translational histone modifications modulate gene expression and kidney injury. Histone crotonylation is a recently described post-translational modification. We hypothesized that histone crotonylation might modulate kidney injury. Histone crotonylation was studied in cultured murine proximal tubular cells and in kidneys from mice with AKI induced by folic acid or cisplatin. Histone lysine crotonylation was observed in tubular cells from healthy murine and human kidney tissue. Kidney tissue histone crotonylation increased during AKI. This was reproduced by exposure to the protein TWEAK in cultured tubular cells. Specifically, ChIP-seq revealed enrichment of histone crotonylation at the genes encoding the mitochondrial biogenesis regulator PGC-1α and the sirtuin-3 decrotonylase in both TWEAK-stimulated tubular cells and in AKI kidney tissue. To assess the role of crotonylation in kidney injury, crotonate was used to increase histone crotonylation in cultured tubular cells or in the kidneys in vivo. Crotonate increased the expression of PGC-1α and sirtuin-3, and decreased CCL2 expression in cultured tubular cells and healthy kidneys. Systemic crotonate administration protected from experimental AKI, preventing the decrease in renal function and in kidney PGC-1α and sirtuin-3 levels as well as the increase in CCL2 expression. For the first time, we have identified factors such as cell stress and crotonate availability that increase histone crotonylation in vivo. Overall, increasing histone crotonylation might have a beneficial effect on AKI. This is the first observation of the in vivo potential of the therapeutic manipulation of histone crotonylation in a disease state. PMID:27125278

  10. Alpinetin inhibits lipopolysaccharide-induced acute kidney injury in mice.

    PubMed

    Huang, Yi; Zhou, Li-shan; Yan, Li; Ren, Juan; Zhou, Dai-xing; Li, Shu-Sheng

    2015-10-01

    Alpinetin, a novel plant flavonoid isolated from Alpinia katsumadai Hayata, has been demonstrated to have anti-inflammatory and antioxidant effects. However, the effects of alpinetin on lipopolysaccharide (LPS)-induced acute kidney injury have not been reported. In the present study, we investigated the protective effects and the underlying mechanism of alpinetin against LPS-induced acute kidney injury in mice. The results showed that alpinetin inhibited LPS-induced kidney histopathologic changes, blood urea nitrogen (BUN) and creatinine levels. Alpinetin also inhibited LPS-induced ROS, MDA, and inflammatory cytokines TNF-α, IL-6 and IL-1β production in kidney tissues. Meanwhile, Western blot analysis showed that alpinetin suppressed LPS-induced TLR4 expression and NF-κB activation in kidney tissues. In addition, alpinetin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, alpinetin protected LPS-induced kidney injury through activating Nrf2 and inhibiting TLR4 expression.

  11. [Acute kidney failure induced by rifampicin].

    PubMed

    Ortiz, A; Barat, A; Oliva, H

    2001-01-01

    A case of acute renal failure requiring dialysis and associated with a characteristic, fulminant clinical course following the intermittent administration of rifampicin is presented. Renal biopsy showed severe tubular injury and a mild interstitial mononuclear cell infiltrate. Withdrawal of rifampicin led to a compete resolution of renal injury. We review the literature on the pathogenesis and treatment of this syndrome and we discuss the different substrates for acute renal failure induced by rifampicin.

  12. Acute kidney injury and dermonecrosis after Loxosceles reclusa envenomation

    PubMed Central

    Nag, A.; Datta, J.; Das, A.; Agarwal, A. K.; Sinha, D.; Mondal, S.; Ete, T.; Chakraborty, A.; Ghosh, S.

    2014-01-01

    Spiders of the Loxosceles species can cause dermonecrosis and acute kidney injury (AKI). Hemolysis, rhabdomyolysis and direct toxin-mediated renal damage have been postulated. There are very few reports of Loxoscelism from India. We report a case of AKI, hemolysis and a “gravitational” pattern of ulceration following the bite of the brown recluse spider (Loxosceles spp). PMID:25097339

  13. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    PubMed Central

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft. PMID:27725836

  14. Nestin(+) kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury.

    PubMed

    Jiang, Mei Hua; Li, Guilan; Liu, Junfeng; Liu, Longshan; Wu, Bingyuan; Huang, Weijun; He, Wen; Deng, Chunhua; Wang, Dong; Li, Chunling; Lahn, Bruce T; Shi, Chenggang; Xiang, Andy Peng

    2015-05-01

    Renal resident mesenchymal stem cells (MSCs) are important regulators of kidney homeostasis, repair or regeneration. However, natural distribution and the starting population properties of these cells remain elusive because of the lack of specific markers. Here, we identified post-natal kidney derived Nestin(+) cells that fulfilled all of the criteria as a mesenchymal stem cell. These isolated Nestin(+) cells expressed the typical cell-surface marker of MSC, including Sca-1, CD44, CD106, NG2 and PDGFR-α. They were capable of self-renewal, possessed high clonogenic potential and extensive proliferation for more than 30 passages. Under appropriate differentiation conditions, these cells could differentiate into adipocytes, osteocytes, chondrocytes and podocytes. After intravenous injection into acute kidney injury mice, Nestin(+) cells contributed to functional improvement by significantly decreasing the peak level of serum creatinine and BUN, and reducing the damaged cell apoptosis. Furthermore, conditioned medium from Nestin(+) cells could protect against ischemic acute renal failure partially through paracrine factor VEGF. Taken together, our findings indicate that renal resident Nestin(+) MSCs can be derived, propagated, differentiated, and repair the acute kidney injury, which may shed new light on understanding MSCs biology and developing cell replacement therapies for kidney disease.

  15. Impact on mortality of the timing of renal replacement therapy in patients with severe acute kidney injury in septic shock: the IDEAL-ICU study (initiation of dialysis early versus delayed in the intensive care unit): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background One of the most dreaded complications of septic shock is acute kidney injury. It occurs in around 50% of patients, with a mortality rate of about 60% at 3 months. There is no consensus on the optimal time to initiate renal replacement therapy. Retrospective and observational studies suggest that early implementation of renal replacement therapy could improve the prognosis for these patients. Methods/design This protocol summarizes the rationale and design of a randomized, controlled, multicenter trial investigating the effect of early versus delayed renal replacement therapy in patients with severe acute kidney injury in early septic shock. In total, 864 critically ill adults with septic shock and evidence of acute kidney injury, defined as the failure stage of the RIFLE classification, will be enrolled. The primary outcome is mortality at 90 days. Secondary outcomes include safety, number of days free of mechanical ventilation, number of days free of renal replacement therapy, intensive care length of stay, in-hospital length of stay, quality of life as evaluated by the EQ-5D and renal replacement therapy dependence at hospital discharge. The primary analysis will be intention to treat. Recruitment started in March 2012 and will be completed by March 2015. Discussion This protocol for a randomized controlled study investigating the impact of the timing of renal replacement therapy initiation should provide an answer to a key question for the management of patients with acute kidney injury in the context of septic shock, for whom the mortality rate remains close to 60% despite improved understanding of physiopathology and recent therapeutic advances. Trial registration ClinicalTrials.gov identifier NCT01682590, registered on 10 September 2012. PMID:24998258

  16. The first case of atrial fibrillation-related graft kidney infarction following acute pyelonephritis.

    PubMed

    Tsai, Shang-Feng

    2014-01-01

    Native renal infarction is uncommon in patients with atrial fibrillation (AF)-related thromboembolism. Graft infarction is also rare, with such cases mostly occurring in the main graft artery postoperatively. To date, there have been no studies of AF-related graft kidney infarction. We herein describe the first case of AF-related graft kidney infarction. The clinical manifestations of this condition mimic and follow those of acute pyelonephritis; therefore, these diseases should be differentially diagnosed as early as possible using lactic dehydrogenase testing and computed tomography. Aggressive treatment with intravascular thrombolysis should be administered, even when the diagnosis is delayed, in order to restore a viable renal function.

  17. Crohnic Kidney Disease: Recurrent Acute Kidney Failure in a Patient With Crohn's Disease

    PubMed Central

    Demir, Mehmet Emin; Ercan, Zafer; Karakas, Emel Yigit; Ulas, Turgay; Buyukhatipoglu, Hakan

    2014-01-01

    Context: Short bowel syndrome is a rare and devastating complication in chronic inflammatory bowel disease following functional or anatomic loss of extensive segments of the intestine. Case Report: A 60-year-old male patient with Crohn's disease had undergone multiple resections of the intestine and developed short bowel syndrome. Despite up to 4-5 liters of orally fluid, sufficient calcium and magnesium intake, he suffered from recurrent acute kidney injury due to profound volume depletion and those electrolyte deficiencies. Administration of intravenous fluid and electrolyte repleacement treatment at regular intervals prevented further kidney injuries. Conclusion: We present a case of recurrent acute kidney failure in a patient with Crohn's disease, and aimed to remark importance of receiving sufficient parenteral fluid and electrolyte support in those with short bowel syndrome. PMID:25599054

  18. Hyperglycemia and Acute Kidney Injury During the Perioperative Period.

    PubMed

    Mendez, Carlos E; Der Mesropian, Paul J; Mathew, Roy O; Slawski, Barbara

    2016-01-01

    Hyperglycemia and acute kidney injury (AKI) are frequently observed during the perioperative period. Substantial evidence indicates that hyperglycemia increases the prevalence of AKI as a surgical complication. Patients who develop hyperglycemia and AKI during the perioperative period are at significantly elevated risk for poor outcomes such as major adverse cardiac events and all-cause mortality. Early observational and interventional trials demonstrated that the use of intensive insulin therapy to achieve strict glycemic control resulted in remarkable reductions of AKI in surgical populations. However, more recent interventional trials and meta-analyses have produced contradictory evidence questioning the renal benefits of strict glycemic control. Although the exact mechanisms through which hyperglycemia increases the risk of AKI have not been elucidated, multiple pathophysiologic pathways have been proposed. Hypoglycemia and glycemic variability may also play a significant role in the development of AKI. In this literature review, the complex relationship between hyperglycemia and AKI as well as its impact on clinical outcomes during the perioperative period is explored.

  19. Metabonomics of acute kidney injury in children after cardiac surgery.

    PubMed

    Beger, Richard D; Holland, Ricky D; Sun, Jinchun; Schnackenberg, Laura K; Moore, Page C; Dent, Catherine L; Devarajan, Prasad; Portilla, Didier

    2008-06-01

    Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.

  20. Plasma FGF23 levels increase rapidly after acute kidney injury

    PubMed Central

    Christov, Marta; Waikar, Sushrut; Pereira, Renata; Havasi, Andrea; Leaf, David E.; Goltzman, David; Pajevic, Paola Divieti; Wolf, Myles; Jüppner, Harald

    2013-01-01

    Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs we used a murine folic acid nephropathy model and found that plasma FGF23 levels increased significantly from baseline already after 1 hour of AKI, with an 18-fold increase at 24 hours. Similar elevations of FGF23 levels were found when AKI was induced in mice with osteocyte-specific parathyroid hormone receptor ablation or the global deletion of parathyroid hormone or vitamin D receptor, indicating that the increase in FGF23 was independent of parathyroid hormone and vitamin D signaling. Furthermore, FGF23 levels increased to a similar extent in wild-type mice maintained on normal or phosphate-depleted diets prior to induction of AKI, indicating that the marked FGF23 elevation is at least partially independent of dietary phosphate. Bone production of FGF23 was significantly increased in AKI. The half-life of intravenously administered recombinant FGF23 was only modestly increased. Consistent with the mouse data, plasma FGF23 levels rose 15.9-fold by 24 hours following cardiac surgery in patients who developed AKI. The levels were significantly higher than in those without postoperative AKI. Thus, circulating FGF23 levels rise rapidly during AKI in rodents and humans. In mice this increase is independent of established modulators of FGF23 secretion. PMID:23657144

  1. Kidney diseases in children - early diagnosis and prevention.

    PubMed

    Polenakovic, Momir; Gucev, Zoran; Tasic, Velibor

    2016-01-01

    Pediatric kidney diseases were in the focus of the World Kidney Day 2016. Macedonian pediatric nephrologists gave their contribution with public appearance in kindergartens, primary and secondary schools, with interactive lectures and discussion with the youngest about the kidney function, healthy life style and simple measures to prevent kidney and urinary tract diseases. Besides promotive appearance in the media, series of lectures were presented in front of the health professionals. The aim was to attract the attention of the professionals for early diagnosis and prevention of kidney disease. The action starts in utero, followed by early postnatal imaging and assessment, conservative treatment and in selected cases surgical treatment. The emphasis is on the multidisciplinary and comprehensive approach to children and adolescents with kidney diseases. PMID:27442411

  2. Kidney diseases in children - early diagnosis and prevention.

    PubMed

    Polenakovic, Momir; Gucev, Zoran; Tasic, Velibor

    2016-01-01

    Pediatric kidney diseases were in the focus of the World Kidney Day 2016. Macedonian pediatric nephrologists gave their contribution with public appearance in kindergartens, primary and secondary schools, with interactive lectures and discussion with the youngest about the kidney function, healthy life style and simple measures to prevent kidney and urinary tract diseases. Besides promotive appearance in the media, series of lectures were presented in front of the health professionals. The aim was to attract the attention of the professionals for early diagnosis and prevention of kidney disease. The action starts in utero, followed by early postnatal imaging and assessment, conservative treatment and in selected cases surgical treatment. The emphasis is on the multidisciplinary and comprehensive approach to children and adolescents with kidney diseases.

  3. Measuring biomarkers of acute kidney injury during renal replacement therapy: wisdom or folly?

    PubMed

    Ostermann, Marlies; Forni, Lui G

    2014-06-19

    Early data are now appearing relating to the measurement of biomarkers of acute kidney injury during renal replacement therapy. These data go some way in describing the clearance of these molecules during renal support. Understanding the potential clearance, or otherwise, of these proteins may lead to directing our therapies in the future particularly with regard to cessation of renal support. We describe a recent study which has provided data that may aid in addressing this issue.

  4. Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.

    PubMed

    Mohamed, Fahim; Buckley, Nicholas A; Jayamanne, Shaluka; Pickering, John W; Peake, Philip; Palangasinghe, Chathura; Wijerathna, Thilini; Ratnayake, Indira; Shihana, Fathima; Endre, Zoltan H

    2015-09-01

    Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning. PMID:26071311

  5. Nutrition for Early Chronic Kidney Disease in Adults

    MedlinePlus

    ... Information Center Medical Education Institute, Inc. (MEI) MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... KB)​​​​​ Alternate Language URL Nutrition for Early Chronic Kidney Disease in Adults Page Content On this page: ...

  6. Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury.

    PubMed

    McKee, Robert A; Wingert, Rebecca A

    2016-01-01

    The kidneys are susceptible to harm from exposure to chemicals they filter from the bloodstream. This can lead to organ injury associated with a rapid decline in renal function and development of the clinical syndrome known as acute kidney injury (AKI). Pharmacological agents used to treat medical circumstances ranging from bacterial infection to cancer, when administered individually or in combination with other drugs, can initiate AKI. Zebrafish are a useful animal model to study the chemical effects on renal function in vivo, as they form an embryonic kidney comprised of nephron functional units that are conserved with higher vertebrates, including humans. Further, zebrafish can be utilized to perform genetic and chemical screens, which provide opportunities to elucidate the cellular and molecular facets of AKI and develop therapeutic strategies such as the identification of nephroprotective molecules. Here, we demonstrate how microinjection into the zebrafish embryo can be utilized as a paradigm for nephrotoxin studies. PMID:27500823

  7. Acute kidney transplant failure following transurethral bladder polyp fulguration.

    PubMed Central

    Collins, Bradley H.; Marroquin, Carlos E.; Tuttle-Newhall, Janet E.; Kuo, Paul C.; Preminger, Glenn M.; Butterly, David W.

    2005-01-01

    Ureteral obstruction and anastomotic leak represent the most common urologic complications of kidney transplantation. Delay in diagnosis or treatment can lead to allograft loss. Obstruction of the ureter occurs in 2% of kidney transplant recipients. Although the majority of cases are immediate technical complications of the operation, subsequent manipulation of the genitourinary system can result in iatrogenic ureteral injury. We report the case of a long-term kidney transplant recipient who developed obstructive uropathy and acute renal failure requiring dialysis after undergoing cystoscopy and bladder polyp fulguration. The etiology was inadvertent thermal injury of the ureteroneocystostomy incurred during the procedure. After attempted percutaneous management, definitive open repair resulted in a return of allograft function to baseline. Images Figure 1 Figure 2 PMID:15779509

  8. Diagnostic Criteria for Acute Kidney Injury: Present and Future

    PubMed Central

    Kellum, John A.

    2015-01-01

    Synopsis Acute kidney injury in a clinical diagnosis guided by standard criteria based on changes in serum creatinine, urine output or both. Severity of acute kidney injury is determined by the magnitude of increase in serum creatinine or decrease in urine output. Patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease and worse outcomes. Both short- and long-term outcomes are worse when patients have some stage of AKI by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. New biomarkers for AKI may substantially aid in the risk assessment and evaluation of patients at risk for AKI. PMID:26410133

  9. New Biomarkers of Acute Kidney Injury and the Cardio-renal Syndrome

    PubMed Central

    2011-01-01

    Changes in renal function are one of the most common manifestations of severe illness. There is a clinical need to intervene early with proven treatments in patients with potentially deleterious changes in renal function. Unfortunately progress has been hindered by poor definitions of renal dysfunction and a lack of early biomarkers of renal injury. In recent years, the definitional problem has been addressed with the establishment of a new well-defined diagnostic entity, acute kidney injury (AKI), which encompasses the wide spectrum of kidney dysfunction, together with clearer definition and sub-classification of the cardio-renal syndromes. From the laboratory have emerged new biomarkers which allow early detection of AKI, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C. This review describes the new concepts of AKI and the cardio-renal syndromes as well as novel biomarkers which allow early detection of AKI. Panels of AKI biomarker tests are likely to revolutionise the diagnosis and management of critically ill patients in the coming years. Earlier diagnosis and intervention should significantly reduce the morbidity and mortality associated with acute kidney damage. PMID:21474979

  10. Pathophysiology of cisplatin-induced acute kidney injury.

    PubMed

    Ozkok, Abdullah; Edelstein, Charles L

    2014-01-01

    Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI). The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality. PMID:25165721

  11. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    PubMed

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities.

  12. Ammonium dichromate poisoning: A rare cause of acute kidney injury

    PubMed Central

    Radhakrishnan, H.; Gopi, M.; Arumugam, A.

    2014-01-01

    Ammonium dichromate is an inorganic compound frequently used in screen and color printing. Being a strong oxidizing agent, it causes oxygen free radical injury resulting in organ failure. We report a 25-year-old female who presented with acute kidney injury after consumption of ammonium dichromate. She was managed successfully with hemodialysis and supportive measures. This case is reported to highlight the toxicity of ammonium dichromate. PMID:25484533

  13. [New mechanisms and recent insights in the pathogenesis of acute kidney injury (AKI)].

    PubMed

    Cantaluppi, Vincenzo; Quercia, Alessandro Domenico; Dellepiane, Sergio; Figliolini, Federico; Medica, Davide; De Lena, Michela

    2012-01-01

    Acute kidney injury (AKI) is a frequent complication in hospitalized patients often associated with multiple organ failure, increased mortality and progression toward chronic kidney disease. The identification of new cellular and molecular targets involved in AKI may lead to an improvement of diagnostic and therapeutic approaches. In recent years, the pathogenetic mechanisms of AKI have been fully elucidated: tubular epithelial cells and endothelial cells present in the microvasculature have been identified as the main targets of ischemia and of nephrotoxic drugs. Indeed, endothelial cell injury is associated with an extension phase of AKI, whereas tubular cells are subjected to an alteration of cell polarity, mislocalization of tight junction proteins and membrane transporters, and finally to the development of necrosis or apotosis. Apoptosis, or programmed cell death, is also a key component of sepsis-associated AKI in which the mechanisms of tissue damage are associated not only with hypoperfusion but also with a direct detrimental effect of bacterial products and inflammatory mediators on resident kidney cells. Endothelial and tubular epithelial cells also represent the main targets in the immunological mechanisms of AKI in kidney transplantation during cell-mediated and antibody-mediated rejection. Recent studies evidenced new molecules as early biomarkers of AKI. Among these molecules, NGAL and KIM-1 play a possible role in the progression toward chronic kidney disease. Lastly, the new frontier of AKI therapy is represented by the use of bone marrow-derived mesenchymal stem cells able to induce a regenerative program in the damaged kidney.

  14. The potential use of biomarkers in predicting contrast-induced acute kidney injury

    PubMed Central

    Andreucci, Michele; Faga, Teresa; Riccio, Eleonora; Sabbatini, Massimo; Pisani, Antonio; Michael, Ashour

    2016-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect.

  15. The potential use of biomarkers in predicting contrast-induced acute kidney injury.

    PubMed

    Andreucci, Michele; Faga, Teresa; Riccio, Eleonora; Sabbatini, Massimo; Pisani, Antonio; Michael, Ashour

    2016-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. PMID:27672338

  16. The potential use of biomarkers in predicting contrast-induced acute kidney injury

    PubMed Central

    Andreucci, Michele; Faga, Teresa; Riccio, Eleonora; Sabbatini, Massimo; Pisani, Antonio; Michael, Ashour

    2016-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. PMID:27672338

  17. Acute kidney injury in critically ill cancer patients: an update.

    PubMed

    Lameire, Norbert; Vanholder, Raymond; Van Biesen, Wim; Benoit, Dominique

    2016-01-01

    Patients with cancer represent a growing group among actual ICU admissions (up to 20 %). Due to their increased susceptibility to infectious and noninfectious complications related to the underlying cancer itself or its treatment, these patients frequently develop acute kidney injury (AKI). A wide variety of definitions for AKI are still used in the cancer literature, despite existing guidelines on definitions and staging of AKI. Alternative diagnostic investigations such as Cystatin C and urinary biomarkers are discussed briefly. This review summarizes the literature between 2010 and 2015 on epidemiology and prognosis of AKI in this population. Overall, the causes of AKI in the setting of malignancy are similar to those in other clinical settings, including preexisting chronic kidney disease. In addition, nephrotoxicity induced by the anticancer treatments including the more recently introduced targeted therapies is increasingly observed. However, data are sometimes difficult to interpret because they are often presented from the oncological rather than from the nephrological point of view. Because the development of the acute tumor lysis syndrome is one of the major causes of AKI in patients with a high tumor burden or a high cell turnover, the diagnosis, risk factors, and preventive measures of the syndrome will be discussed. Finally, we will briefly discuss renal replacement therapy modalities and the emergence of chronic kidney disease in the growing subgroup of critically ill post-AKI survivors. PMID:27480256

  18. Impact of an Early Invasive Strategy versus Conservative Strategy for Unstable Angina and Non-ST Elevation Acute Coronary Syndrome in Patients with Chronic Kidney Disease: A Systematic Review

    PubMed Central

    Shaw, Catriona; Nitsch, Dorothea; Lee, Jasmine; Fogarty, Damian; Sharpe, Claire C.

    2016-01-01

    Background Clinical practice guidelines support an early invasive approach after NSTE-ACS in patients with chronic kidney disease (CKD). There is no direct randomised controlled trial evidence in the CKD population, and whether the benefit of an early invasive approach is maintained across the spectrum of severity of CKD remains controversial. Methods We conducted a systematic review to evaluate the association between an early invasive approach and all-cause mortality in patients with CKD. We searched MEDLINE and EMBASE (1990-May 2015) and article reference lists. Data describing study design, participants, invasive management strategies, renal function, all-cause mortality and risk of bias were extracted. Results 3,861 potentially relevant studies were identified. Ten studies, representing data on 147,908 individuals with NSTE-ACS met the inclusion criteria. Qualitative heterogeneity in the definitions of early invasive approach, comparison groups and renal dysfunction existed. Meta-analysis of the RCT derived and observational data were generally supportive of an early invasive approach in CKD (RR0.76 (95% CI 0.49–1.17) and RR0.50 (95%CI 0.42–0.59) respectively). Meta-analysis of the observational studies demonstrated a large degree of heterogeneity (I2 79%) driven in part by study size and heterogeneity across various kidney function levels. Conclusions The observational data support that an early invasive approach after NSTE-ACS confers a survival benefit in those with early-moderate CKD. Local opportunities for quality improvement should be sought. Those with severe CKD and the dialysis population are high risk and under-studied. Novel and inclusive approaches for CKD and dialysis patients in cardiovascular clinical trials are needed. PMID:27195786

  19. Acute kidney injury: changing lexicography, definitions, and epidemiology.

    PubMed

    Himmelfarb, J; Ikizler, T A

    2007-05-01

    In recent years, there have been numerous advances in understanding the molecular determinants of functional kidney injury after ischemic and/or toxic exposure. However, translation of successful novel therapies designed to attenuate kidney functional injury from animal models to the clinical sphere has had modest results. This lack of translatability is at least in part due to lack of sufficient standardization in definitions and classification of cases of acute kidney injury (AKI), an incomplete understanding of the natural history of human AKI, and a limited understanding of how kidney injury interacts with other organ system failure in the context of systemic metabolic abnormalities. A concerted effort is now being made by nephrologists and intensivists to arrive at standardized terminology and classification of AKI. There have also been dramatic advances in our understanding of the epidemiology and natural history of AKI, particularly in the hospital and intensive care unit setting. Promising strategies are now being developed which may ultimately lead to improved outcomes for patients at risk for or who have developed AKI, which should be readily testable in the coming decade.

  20. Biomarkers of acute kidney injury and associations with short- and long-term outcomes

    PubMed Central

    Schaub, Jennifer A.; Parikh, Chirag R.

    2016-01-01

    Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury. PMID:27239295

  1. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria

    PubMed Central

    Agarwal, Banwari; Davenport, Andrew

    2014-01-01

    Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease (MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period. PMID:25349641

  2. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products.

  3. Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury

    PubMed Central

    Cheng, Shun-Yang; Chou, Yu-Hsiang; Liao, Fang-Ling; Lin, Chi-Chun; Chang, Fan-Chi; Liu, Chia-Hao; Huang, Tao-Min; Lai, Chun-Fu; Lin, Yu-Feng; Wu, Vin-Cent; Chu, Tzong-Shinn; Wu, Ming-Shiou; Lin, Shuei-Liong

    2016-01-01

    Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI. PMID:27677327

  4. TNFR1-dependent pulmonary apoptosis during ischemic acute kidney injury.

    PubMed

    White, Laura E; Santora, Rachel J; Cui, Yan; Moore, Frederick A; Hassoun, Heitham T

    2012-09-01

    Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1-/- mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets.

  5. TNFR1-dependent pulmonary apoptosis during ischemic acute kidney injury

    PubMed Central

    White, Laura E.; Santora, Rachel J.; Cui, Yan; Moore, Frederick A.

    2012-01-01

    Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1−/− mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets. PMID:22728466

  6. [Urinalysis in patients at the early stage of acute pancreatitis].

    PubMed

    Rybak, Katarzyna; Sporek, Mateusz; Gala-Błądzińska, Agnieszka; Mazur-Laskowska, Małgorzata; Dumnicka, Paulina; Walocha, Jerzy; Drożdż, Ryszard; Kuźniewski, Marek; Ceranowicz, Piotr; Kuśnierz-Cabala, Beata

    2016-01-01

    Urinalysis is a routine and cheap laboratory test that provides clinically useful information in patients with acute abdominal conditions, including acute pancreatitis. The aim of the study was to assess the relationships between the results of urinalysis and the course of the disease among 65 patients with acute pancreatitis (34 men and 31 women, mean age 61 ± 19 years) at the early phase of the disease, i.e. during the first 72 hours from the onset of symptoms. Mild acute pancreatitis was diagnosed in 47 patients, moderately severe in 13 and severe in 5. The most prevalent abnormalities were proteinuria (43% of patients), high urinary bilirubin (20%), erythrocytes (18%), glucose (18%) and leukocytes (17%). High urinary protein and low specific gravity were associated with more severe acute disease and with acute kidney injury. The severity of bilirubinuria and proteinuria were positively correlated with urine concentrations of neutrophil gelatinase associated lipocalin (NGAL). Urinalysis should be routinely performed in patients with acute pancreatitis. PMID:27197429

  7. Outpatient nephrology referral rates after acute kidney injury.

    PubMed

    Siew, Edward D; Peterson, Josh F; Eden, Svetlana K; Hung, Adriana M; Speroff, Theodore; Ikizler, T Alp; Matheny, Michael E

    2012-02-01

    AKI associates with an increased risk for the development and progression of CKD and mortality. Processes of care after an episode of AKI are not well described. Here, we examined the likelihood of nephrology referral among survivors of AKI at risk for subsequent decline in kidney function in a US Department of Veterans Affairs database. We identified 3929 survivors of AKI hospitalized between January 2003 and December 2008 who had an estimated GFR (eGFR) <60 ml/min per 1.73 m(2) 30 days after peak injury. We analyzed time to referral considering improvement in kidney function (eGFR ≥60 ml/min per 1.73 m(2)), dialysis initiation, and death as competing risks over a 12-month surveillance period. Median age was 73 years (interquartile range, 62-79 years) and the prevalence of preadmission kidney dysfunction (baseline eGFR <60 ml/min per 1.73 m(2)) was 60%. Overall mortality during the surveillance period was 22%. The cumulative incidence of nephrology referral before dying, initiating dialysis, or experiencing an improvement in kidney function was 8.5% (95% confidence interval, 7.6-9.4). Severity of AKI did not affect referral rates. These data demonstrate that a minority of at-risk survivors are referred for nephrology care after an episode of AKI. Determining how to best identify survivors of AKI who are at highest risk for complications and progression of CKD could facilitate early nephrology-based interventions.

  8. The long-term prognosis of acute kidney injury: acute renal failure as a cause of chronic kidney disease.

    PubMed

    Basile, Carlo

    2008-01-01

    There is a widespread opinion that acute kidney injury (AKI) is a rather harmless complication and that survival is determined not by renal dysfunction per se, but by the severity of the underlying disease. This opinion is in sharp contrast to evidence from several recent experimental and clinical investigations indicating that AKI is a condition which exerts a fundamental impact on the course of the disease, the evolution of associated complications and on prognosis, independently from the type and severity of the underlying condition. In conclusion, severe AKI in the critically ill patient is associated with high rates of morbidity, mortality and consumption of health care resources.

  9. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    PubMed Central

    Duann, Pu; Lianos, Elias A.; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  10. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury

    PubMed Central

    Ahn, Seung Won; Kim, Tong Yoon; Lee, Sangmin; Jeong, Jeong Yeon; Shim, Hojoon; Han, Yu min; Choi, Kyu Eun; Shin, Seok Joon; Yoon, Hye Eun

    2016-01-01

    Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice. PMID:27536162

  11. Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention

    PubMed Central

    Faga, Teresa; Pisani, Antonio; Michael, Ashour

    2014-01-01

    It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

  12. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury.

    PubMed

    Duann, Pu; Lianos, Elias A; Ma, Jianjie; Lin, Pei-Hui

    2016-01-01

    Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed. PMID:27153058

  13. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; Zaltzman, Jeffrey S

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID:26258081

  14. Coupled plasma filtration adsorption for the treatment of a patient with acute respiratory distress syndrome and acute kidney injury: a case report.

    PubMed

    Lucisano, Gaetano; Capria, Maria; Matera, Giovanni; Presta, Pierangela; Comi, Nicolino; Talarico, Roberta; Rametti, Linda; Quirino, Angela; Giancotti, Aida; Fuiano, Giorgio

    2011-10-01

    Coupled plasma filtration adsorption (CPFA) is an extracorporeal blood purification therapy based on non-specific pro- and anti-inflammatory mediator adsorption on a special resin cartridge coupled with continuous veno-venous haemofiltration or continuous veno-venous haemodiafiltration and is one of the emerging treatments for septic patients. However, in the literature, there are limited data about its efficacy in treating patients with acute diseases but without the traditional criteria for sepsis. We describe the case of a 43-year-old male who developed acute respiratory distress syndrome secondary to pneumonia and acute kidney injury, whose clinical conditions rapidly improved after early CPFA therapy.

  15. Coupled plasma filtration adsorption for the treatment of a patient with acute respiratory distress syndrome and acute kidney injury: a case report

    PubMed Central

    Lucisano, Gaetano; Capria, Maria; Matera, Giovanni; Presta, Pierangela; Comi, Nicolino; Talarico, Roberta; Rametti, Linda; Quirino, Angela; Giancotti, Aida

    2011-01-01

    Coupled plasma filtration adsorption (CPFA) is an extracorporeal blood purification therapy based on non-specific pro- and anti-inflammatory mediator adsorption on a special resin cartridge coupled with continuous veno-venous haemofiltration or continuous veno-venous haemodiafiltration and is one of the emerging treatments for septic patients. However, in the literature, there are limited data about its efficacy in treating patients with acute diseases but without the traditional criteria for sepsis. We describe the case of a 43-year-old male who developed acute respiratory distress syndrome secondary to pneumonia and acute kidney injury, whose clinical conditions rapidly improved after early CPFA therapy. PMID:25984170

  16. Hyperglycemia and acute kidney injury in critically ill children

    PubMed Central

    Gordillo, Roberto; Ahluwalia, Tania; Woroniecki, Robert

    2016-01-01

    Background Hyperglycemia and acute kidney injury (AKI) are common in critically ill children and have been associated with higher morbidity and mortality. The incidence of AKI in children is difficult to estimate because of the lack of a standard definition for AKI. The pediatric RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria can be used to define AKI in children. Various biomarkers in urine and blood have been studied to detect AKI in critically ill children. However, it is not clear whether hyperglycemia is associated with AKI. Our objective was to evaluate the effect of hyperglycemia on kidney function and its effect on neutrophil gelatinase-associated lipocalin (NGAL) in children. Methods We studied retrospective and prospective cohorts of pediatric critically ill subjects admitted to the pediatric intensive care unit (PICU). We analyzed data from admission that included estimated glomerular filtration rate, plasma and urine NGAL, serum glucose and peak glycemia (highest glycemia during PICU admission), and length of hospital and PICU stay from two different institutions. Results We found that the prevalence of hyperglycemia was 89% in the retrospective cohort and 86% in the prospective cohort, P=0.99. AKI was associated with peak glycemia, P=0.03. There was a statistically significant correlation between peak glycemia and hospital and PICU stays, P=<0.001 and P<0.001, respectively. Urine NGAL and plasma NGAL were not statistically different in subjects with and without hyperglycemia, P=0.99 and P=0.85, respectively. Subjects on vasopressors had lower estimated glomerular filtration rate and higher glycemia, P=0.01 and P=0.04, respectively. Conclusion We conclude that in critically ill children, hyperglycemia is associated with AKI and longer PICU stays. PMID:27601931

  17. Bilateral renal lymphoma: rapid recovery from an acute kidney injury after open renal biopsy.

    PubMed

    Mitome, Taku; Furuya, Kazuhiro; Imano, Masashi; Osaka, Kimito; Yokomizo, Yumiko; Hayashi, Narihiko; Nakaigawa, Noboru; Yamanaka, Shoji; Yao, Masahiro

    2016-01-01

    Renal lymphoma as an initial lesion is relatively rare. Bilateral renal lymphoma frequently presents as acute kidney injury. With systematic chemotherapy for the lymphoma, patients usually recover their kidney function. However, in the case we describe here, the patient's kidney function recovered greatly after an open renal biopsy. Here, we review and discuss this unique case.

  18. Rare allergic reaction of the kidney: sitagliptin-induced acute tubulointerstitial nephritis.

    PubMed

    Alsaad, Ali A; Dhannoon, Sarah M; Pantin, Sally-Ann L; Porter, Ivan E

    2016-01-01

    A 56-year-old man with a history of diabetes mellitus type-2 and stage-2 chronic kidney disease secondary to diabetic nephropathy presented with an acute deterioration of kidney function. Non-invasive work-up failed to reveal the underlying aetiology for the acute kidney failure. Kidney biopsy revealed acute tubulointerstitial nephritis (ATIN) which was attributed to sitagliptin use. Only few case reports have shown this correlation. Our aim is to alert physicians and other providers of the potential effect of sitagliptin to cause ATIN with this biopsy-proven case. PMID:27436034

  19. Hemojuvelin Modulates Iron Stress During Acute Kidney Injury: Improved by Furin Inhibitor

    PubMed Central

    Young, Guang-Huar; Huang, Tao-Min; Wu, Che-Hsiung; Lai, Chun-Fu; Hou, Chun-Cheng; Peng, Kang-Yung; Liang, Chan-Jung; Lin, Shuei-Liong; Chang, Shih-Chung; Tsai, Pi-Ru; Wu, Kwan-Dun

    2014-01-01

    Abstract Aims: Free iron plays an important role in the pathogenesis of acute kidney injury (AKI) via the formation of hydroxyl radicals. Systemic iron homeostasis is controlled by the hemojuvelin-hepcidin-ferroportin axis in the liver, but less is known about this role in AKI. Results: By proteomics, we identified a 42 kDa soluble hemojuvelin (sHJV), processed by furin protease from membrane-bound hemojuvelin (mHJV), in the urine during AKI after cardiac surgery. Biopsies from human and mouse specimens with AKI confirm that HJV is extensively increased in renal tubules. Iron overload enhanced the expression of hemojuvelin-hepcidin signaling pathway. The furin inhibitor (FI) decreases furin-mediated proteolytic cleavage of mHJV into sHJV and augments the mHJV/sHJV ratio after iron overload with hypoxia condition. The FI could reduce renal tubule apoptosis, stabilize hypoxic induced factor-1, prevent the accumulation of iron in the kidney, and further ameliorate ischemic-reperfusion injury. mHJV is associated with decreasing total kidney iron, secreting hepcidin, and promoting the degradation of ferroportin at AKI, whereas sHJV does the opposite. Innovation: This study suggests the ratio of mHJV/sHJV affects the iron deposition during acute kidney injury and sHJV could be an early biomarker of AKI. Conclusion: Our findings link endogenous HJV inextricably with renal iron homeostasis for the first time, add new significance to early predict AKI, and identify novel therapeutic targets to reduce the severity of AKI using the FI. Antioxid. Redox Signal. 20, 1181–1194. PMID:23901875

  20. Outpatient Nephrology Referral Rates after Acute Kidney Injury

    PubMed Central

    Siew, Edward D.; Peterson, Josh F.; Eden, Svetlana K.; Hung, Adriana M.; Speroff, Theodore; Ikizler, T. Alp

    2012-01-01

    AKI associates with an increased risk for the development and progression of CKD and mortality. Processes of care after an episode of AKI are not well described. Here, we examined the likelihood of nephrology referral among survivors of AKI at risk for subsequent decline in kidney function in a US Department of Veterans Affairs database. We identified 3929 survivors of AKI hospitalized between January 2003 and December 2008 who had an estimated GFR (eGFR) <60 ml/min per 1.73 m2 30 days after peak injury. We analyzed time to referral considering improvement in kidney function (eGFR ≥60 ml/min per 1.73 m2), dialysis initiation, and death as competing risks over a 12-month surveillance period. Median age was 73 years (interquartile range, 62–79 years) and the prevalence of preadmission kidney dysfunction (baseline eGFR <60 ml/min per 1.73 m2) was 60%. Overall mortality during the surveillance period was 22%. The cumulative incidence of nephrology referral before dying, initiating dialysis, or experiencing an improvement in kidney function was 8.5% (95% confidence interval, 7.6–9.4). Severity of AKI did not affect referral rates. These data demonstrate that a minority of at-risk survivors are referred for nephrology care after an episode of AKI. Determining how to best identify survivors of AKI who are at highest risk for complications and progression of CKD could facilitate early nephrology-based interventions. PMID:22158435

  1. Hsp72 Is a Novel Biomarker to Predict Acute Kidney Injury in Critically Ill Patients

    PubMed Central

    Morales-Buenrostro, Luis E.; Salas-Nolasco, Omar I.; Barrera-Chimal, Jonatan; Casas-Aparicio, Gustavo; Irizar-Santana, Sergio; Pérez-Villalva, Rosalba; Bobadilla, Norma A.

    2014-01-01

    Background and Objectives Acute kidney injury (AKI) complicates the course of disease in critically ill patients. Efforts to change its clinical course have failed because of the fail in the early detection. This study was designed to assess whether heat shock protein (Hsp72) is an early and sensitive biomarker of acute kidney injury (AKI) compared with kidney injury molecule (Kim-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) biomarkers. Methods A total of 56 critically ill patients fulfilled the inclusion criteria. From these patients, 17 developed AKI and 20 were selected as controls. In AKI patients, Kim-1, IL-18, NGAL, and Hsp72 were measured from 3 days before and until 2 days after the AKI diagnosis and in no-AKI patients at 1, 5 and 10 days after admission. Biomarker sensitivity and specificity were determined. To validate the results obtained with ROC curves for Hsp72, a new set of critically ill patients was included, 10 with AKI and 12 with no-AKI patients. Results Urinary Hsp72 levels rose since 3 days before the AKI diagnosis in critically ill patients; this early increase was not seen with any other tested biomarkers. Kim-1, IL-18, NGAL, and Hsp72 significantly increased from 2 days before AKI and remained elevated during the AKI diagnosis. The best sensitivity/specificity was observed in Kim-1 and Hsp72: 83/95% and 100/90%, respectively, whereas 1 day before the AKI diagnosis, the values were 100/100% and 100/90%, respectively. The sensibility, specificity and accuracy in the validation test for Hsp72 were 100%, 83.3% and 90.9%, respectively. Conclusions The biomarker Hsp72 is enough sensitive and specific to predict AKI in critically ill patients up to 3 days before the diagnosis. PMID:25313566

  2. Development of an Immunoassay for the Kidney Specific Protein myo-Inositol Oxygenase, a Potential Biomarker of Acute Kidney Injury

    PubMed Central

    Gaut, Joseph P.; Crimmins, Dan L.; Ohlendorf, Matt F.; Lockwood, Christina M.; Griest, Terry A.; Brada, Nancy A.; Hoshi, Masato; Sato, Bryan; Hotchkiss, Richard S.; Jain, Sanjay; Ladenson, Jack H.

    2014-01-01

    Background Acute kidney injury (AKI) affects 45% of critically ill patients resulting in increased morbidity and mortality. The diagnostic standard, serum creatinine (SCr), is non-specific and may not increase until days after injury. There is significant need for a renal specific AKI biomarker detectable early enough that there would be a potential window for therapeutic intervention. In this study, we sought to identify a renal specific biomarker of AKI. Methods Gene expression data was analyzed from normal mouse tissues to identify kidney specific genes, one of which was Miox. Monoclonal antibodies were generated to recombinant myo-inositol oxygenase (MIOX), and an immunoassay was developed to quantify MIOX in plasma. The immunoassay was tested in animals and retrospectively in patients with and without AKI. Results Kidney tissue specificity of MIOX was supported by Western blot. Immunohistochemistry localized MIOX to the proximal renal tubule. Plasma MIOX, undetectable at baseline, increased 24 hours following AKI in mice. Plasma MIOX was increased in critically ill patients with AKI (12.4 ± 4.3 ng/mL, n=42) compared with patients without AKI (0.5 ± 0.3 ng/mL, n=17) and was highest in patients with oliguric AKI (20.2 ± 7.5 ng/mL, n=23). Plasma MIOX increased 54.3 ± 3.8 hours before the increase in SCr. Conclusions MIOX is a renal specific, proximal tubule protein that is increased in plasma of animals and critically ill patients with AKI. MIOX preceded the elevation in SCr by approximately two days in human patients. Large-scale studies are warranted to further investigate MIOX as an AKI biomarker. PMID:24486646

  3. [Epidemiology of acute kidney injury in hospitalized patients in China].

    PubMed

    Lang, Xiabing; Yang, Yi; Chen, Jianghua

    2016-03-01

    Acute kidney injury (AKI) is a disease spectrum ranging from minimal elevation of serum creatinine to complete renal failure. It is significantly associated with increased mortality, length of hospital stay and medical care cost. With the increasing awareness of the importance of AKI, several high quality and multicenter epidemiological studies have been published recently in China. However, the results differ a lot due to the differences in regional economic development, the selection of target population and testing indicators, the disease definition and study strategies. The reported incidence of AKI in China is much lower than that in the developed countries. This article will analyze the current status and the problems facing AKI epidemiological studies of hospitalized patients with our own data and those from literature. The article intends to clarify the burden of AKI,to increase the awareness of AKI among clinicians and policy makers for achieving the goal of "zero by 2025" in China. PMID:27273996

  4. Acute kidney injury after massive attack of Africanised bees

    PubMed Central

    Bridi, Ramaiane A; Balbi, Andre Luis; Neves, Precil M; Ponce, Daniela

    2014-01-01

    Acute kidney injury (AKI) is a well-documented complication of massive attack by Africanised bees and can be observed 48–72 h after the accident. We report a case of Africanised bees attack followed by severe and lethal AKI. A 56-year-old man was admitted to emergency department after a massive attack of Africanised bees (>1000 bee stings). He was unconscious, presenting with hypotension and tachycardia. Mechanical ventilation, volume expansion and care for anaphylaxis were instituted. The patient was transferred to the intensive care unit (ICU) and after 48 h he developed rhabdomyolysis, oliguria, increased creatinine levels, hyperkalaemia and refractory acidosis. A diagnosis of AKI secondary to rhabdomyolysis and shock was made. The patient was treated with a prolonged course of haemodialysis. However, he progressed to refractory shock and died 5 days after admission. PMID:24618864

  5. Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction

    PubMed Central

    de Matos, Ana Cristina Carvalho; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; de Arruda, Érika Ferraz; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

    2015-01-01

    ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID:26154553

  6. Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction.

    PubMed

    Matos, Ana Cristina Carvalho de; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão Junior, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; Arruda, Érika Ferraz de; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

    2015-01-01

    Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction.

  7. Acute Kidney Injury Increases Risk of ESRD among Elderly

    PubMed Central

    Ishani, Areef; Xue, Jay L.; Himmelfarb, Jonathan; Eggers, Paul W.; Kimmel, Paul L.; Molitoris, Bruce A.; Collins, Allan J.

    2009-01-01

    Risk for ESRD among elderly patients with acute kidney injury (AKI) has not been studied in a large, representative sample. This study aimed to determine incidence rates and hazard ratios for developing ESRD in elderly individuals, with and without chronic kidney disease (CKD), who had AKI. In the 2000 5% random sample of Medicare beneficiaries, clinical conditions were identified using Medicare claims; ESRD treatment information was obtained from ESRD registration during 2 yr of follow-up. Our cohort of 233,803 patients were hospitalized in 2000, were aged ≥67 yr on discharge, did not have previous ESRD or AKI, and were Medicare-entitled for ≥2 yr before discharge. In this cohort, 3.1% survived to discharge with a diagnosis of AKI, and 5.3 per 1000 developed ESRD. Among patients who received treatment for ESRD, 25.2% had a previous history of AKI. After adjustment for age, gender, race, diabetes, and hypertension, the hazard ratio for developing ESRD was 41.2 (95% confidence interval [CI] 34.6 to 49.1) for patients with AKI and CKD relative to those without kidney disease, 13.0 (95% CI 10.6 to 16.0) for patients with AKI and without previous CKD, and 8.4 (95% CI 7.4 to 9.6) for patients with CKD and without AKI. In summary, elderly individuals with AKI, particularly those with previously diagnosed CKD, are at significantly increased risk for ESRD, suggesting that episodes of AKI may accelerate progression of renal disease. PMID:19020007

  8. Acute kidney injury increases risk of ESRD among elderly.

    PubMed

    Ishani, Areef; Xue, Jay L; Himmelfarb, Jonathan; Eggers, Paul W; Kimmel, Paul L; Molitoris, Bruce A; Collins, Allan J

    2009-01-01

    Risk for ESRD among elderly patients with acute kidney injury (AKI) has not been studied in a large, representative sample. This study aimed to determine incidence rates and hazard ratios for developing ESRD in elderly individuals, with and without chronic kidney disease (CKD), who had AKI. In the 2000 5% random sample of Medicare beneficiaries, clinical conditions were identified using Medicare claims; ESRD treatment information was obtained from ESRD registration during 2 yr of follow-up. Our cohort of 233,803 patients were hospitalized in 2000, were aged > or = 67 yr on discharge, did not have previous ESRD or AKI, and were Medicare-entitled for > or = 2 yr before discharge. In this cohort, 3.1% survived to discharge with a diagnosis of AKI, and 5.3 per 1000 developed ESRD. Among patients who received treatment for ESRD, 25.2% had a previous history of AKI. After adjustment for age, gender, race, diabetes, and hypertension, the hazard ratio for developing ESRD was 41.2 (95% confidence interval [CI] 34.6 to 49.1) for patients with AKI and CKD relative to those without kidney disease, 13.0 (95% CI 10.6 to 16.0) for patients with AKI and without previous CKD, and 8.4 (95% CI 7.4 to 9.6) for patients with CKD and without AKI. In summary, elderly individuals with AKI, particularly those with previously diagnosed CKD, are at significantly increased risk for ESRD, suggesting that episodes of AKI may accelerate progression of renal disease.

  9. Contrast-Induced Acute Kidney Injury: Definition, Epidemiology, and Outcome

    PubMed Central

    Meinel, Felix G.; De Cecco, Carlo N.; Schoepf, U. Joseph

    2014-01-01

    Contrast-induced acute kidney injury (CI-AKI) is commonly defined as a decline in kidney function occurring in a narrow time window after administration of iodinated contrast material. The incidence of AKI after contrast material administration greatly depends on the specific definition and cutoff values used. Although self-limiting in most cases, postcontrast AKI carries a risk of more permanent renal insufficiency, dialysis, and death. The risk of AKI from contrast material, in particular when administered intravenously for contrast-enhanced CT, has been exaggerated by older, noncontrolled studies due to background fluctuations in renal function. More recent evidence from controlled studies suggests that the risk is likely nonexistent in patients with normal renal function, but there may be a risk in patients with renal insufficiency. However, even in this patient population, the risk of CI-AKI is probably much smaller than traditionally assumed. Since volume expansion is the only preventive strategy with a convincing evidence base, liberal hydration should be encouraged to further minimize the risk. The benefits of the diagnostic information gained from contrast-enhanced examinations will still need to be balanced with the potential risk of CI-AKI for the individual patient and clinical scenario. PMID:24734250

  10. Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury

    PubMed Central

    Schley, Gunnar; Köberle, Carmen; Manuilova, Ekaterina; Rutz, Sandra; Forster, Christian; Weyand, Michael; Formentini, Ivan; Kientsch-Engel, Rosemarie; Eckardt, Kai-Uwe; Willam, Carsten

    2015-01-01

    Background New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma. Methods This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. Results Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. Conclusions In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed

  11. Oral bisphosphonate use in the elderly is not associated with acute kidney injury.

    PubMed

    Shih, Andrew W Y; Weir, Matthew A; Clemens, Kristin K; Yao, Zhan; Gomes, Tara; Mamdani, Muhammad M; Juurlink, David N; Hird, Amanda; Hodsman, Anthony; Parikh, Chirag R; Wald, Ron; Cadarette, Suzanne M; Garg, Amit X

    2012-10-01

    Intravenous bisphosphonates can cause acute kidney injury; however, this risk was not found with oral bisphosphonates in randomized clinical trials with restrictive eligibility criteria. In order to provide complementary safety data, we studied the risk of acute kidney injury in a population-based cohort of 122,727 patients aged 66 years and older discharged from hospital following a new fragility fracture and no history of bisphosphonate use in the prior year. Bisphosphonate treatment was identified within 120 days after discharge and event rates were measured from 90 days of therapy initiation. The primary outcome was hospitalization with acute kidney injury with secondary outcomes of new nephrology consultation and, in a subset of patients with laboratory values, acute kidney injury was defined as an increase in serum creatinine. We identified 18,286 bisphosphonate users and 104,441 non-users with a mean age of 81 years. Of 5772 patients with laboratory values, 40% had chronic kidney disease (eGFR <60 ml/min per 1.73 m(2)). Overall, there was no statistically significant difference in the risk of acute kidney injury among bisphosphonate users compared to non-users (adjusted odds ratio 1.03), and no significant differences in other outcomes or in subgroups of patients with baseline chronic kidney disease. Thus, in this older population-based cohort, oral bisphosphonate use was not associated with acute kidney injury.

  12. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.

    PubMed

    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Manicassamy, Santhakumar; Ramesh, Ganesan

    2013-11-15

    Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

  13. Incidence and Risk Factors for Acute Kidney Injury Following Mannitol Infusion in Patients With Acute Stroke

    PubMed Central

    Lin, Shin-Yi; Tang, Sung-Chun; Tsai, Li-Kai; Yeh, Shin-Joe; Shen, Li-Jiuan; Wu, Fe-Lin Lin; Jeng, Jiann-Shing

    2015-01-01

    Abstract Mannitol, an osmotic diuretic, is commonly used to treat patients with acute brain edema, but its use also increases the risk of developing acute kidney injury (AKI). In this study, we investigated the incidence and risk factors of mannitol-related AKI in acute stroke patients. A total of 432 patients (ischemic stroke 62.3%) >20 years of age who were admitted to the neurocritical care center in a tertiary hospital and received mannitol treatment were enrolled in this study. Clinical parameters including the scores of National Institutes of Health Stroke Scale (NIHSS) at admission, vascular risk factors, laboratory data, and concurrent nephrotoxic medications were registered. Acute kidney injury was defined as an absolute elevation in the serum creatinine (Scr) level of ≥0.3 mg/dL from the baseline or a ≥50% increase in Scr. The incidence of mannitol-related AKI was 6.5% (95% confidence interval, 4.5%–9.3%) in acute stroke patients, 6.3% in patients with ischemic stroke, and 6.7% in patients with intracerebral hemorrhage. Multivariate analysis revealed that diabetes, lower estimated glomerular filtration rate at baseline, higher initial NIHSS score, and concurrent use of diuretics increased the risk of mannitol-related AKI. When present, the combination of these elements displayed an area under the receiver operating characteristic curve of 0.839 (95% confidence interval, 0.770–0.909). In conclusion, mannitol-related AKI is not uncommon in the treatment of acute stroke patients, especially in those with vulnerable risk factors. PMID:26632702

  14. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    PubMed Central

    Ayoob, Rose M.

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies. PMID:27642522

  15. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis.

    PubMed

    Ayoob, Rose M; Schwaderer, Andrew L

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies. PMID:27642522

  16. Nonapoptotic cell death in acute kidney injury and transplantation.

    PubMed

    Linkermann, Andreas

    2016-01-01

    Acute tubular necrosis causes a loss of renal function, which clinically presents as acute kidney failure (AKI). The biochemical signaling pathways that trigger necrosis have been investigated in detail over the past 5 years. It is now clear that necrosis (regulated necrosis, RN) represents a genetically driven process that contributes to the pathophysiology of AKI. RN pathways such as necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-induced regulated necrosis (MPT-RN) may be mechanistically distinct, and the relative contributions to overall organ damage during AKI in living organisms largely remain elusive. In a synchronized manner, some necrotic programs induce the breakdown of tubular segments and multicellular functional units, whereas others are limited to killing single cells in the tubular compartment. Importantly, the means by which a renal cell dies may have implications for the subsequent inflammatory response. In this review, the recent advances in the field of renal cell death in AKI and key enzymes that might serve as novel therapeutic targets will be discussed. As a consequence of the interference with RN, the immunogenicity of dying cells in AKI in renal transplants will be diminished, rendering inhibitors of RN indirect immunosuppressive agents. PMID:26759047

  17. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

    PubMed Central

    Ayoob, Rose M.

    2016-01-01

    The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN) usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males), mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies.

  18. The severity of acute kidney injury predicts progression to chronic kidney disease

    PubMed Central

    Chawla, Lakhmir S; Amdur, Richard L; Amodeo, Susan; Kimmel, Paul L; Palant, Carlos E

    2011-01-01

    Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with ‘c' statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy (‘c' 0.81–0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD. PMID:21430640

  19. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration. PMID:25500295

  20. Neuroimmune Control of Acute Kidney Injury and Inflammation

    PubMed Central

    Inoue, Tsuyoshi; Okusa, Mark D.

    2015-01-01

    Despite major advances in identifying pathophysiological mechanisms of acute kidney injury (AKI), no definitive therapeutic or preventive modalities have been developed with the exception of dialysis. One possible approach is the control of inflammation and AKI through activation of the neuro-immune axis. The cholinergic anti-inflammatory pathway is thought to contribute to the homeostatic response to inflammation-related disorders and forms the basis for recent approaches to therapeutic intervention. The concept is based on the emerging understanding of the interface between the nervous and immune systems. In the cholinergic anti-inflammatory pathway, the efferent vagus nerve indirectly stimulates the CD4+ T cells in the spleen. The CD4+ T cells produce acetylcholine, which stimulates alpha 7 nicotinic receptors (α7nAch) on macrophages. Activation of the α7nAch receptors on macrophages activates NF-κβ and elicits an anti-inflammatory response. Recently we demonstrated the effect of a non-pharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia-reperfusion injury and sepsis-induced AKI in mice. Our data suggest that ultrasound-induced tissue protection is mediated through the activation of the cholinergic anti-inflammatory pathway. In addition, nicotinic receptor agonists and ghrelin, a neuropeptide, were reported to prevent AKI possibly through a mechanism closely linked with vagus nerve stimulation. Based on the studies focusing on inflammation and the observations regarding kidney injury, we believe that activating the cholinergic anti-inflammatory pathway will be a new modality for the prevention and treatment of AKI. PMID:26376049

  1. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    PubMed Central

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  2. Update in sepsis and acute kidney injury 2014.

    PubMed

    Schortgen, Frédérique; Asfar, Pierre

    2015-06-01

    Sepsis and acute kidney injury (AKI) represent an important burden in intensive care unit clinical practices. The Journal published important contributions in sepsis for novel therapeutic approaches suggesting that combined molecular targets (e.g., dual inhibition of IL-1β and IL-18, and coadministration of endothelial progenitor cells and stromal cell-derived factor-1α analog) could perform better. The clinical effectiveness of 1,25-dihydroxyvitamin D was reported in a double-blind, randomized, placebo-controlled trial. Although its experimental properties appeared favorable in the pro- and antiinflammatory cytokine balance, 1,25-dihydroxyvitamin D failed to improve survival. Strategies for decreasing antimicrobial resistances are of particular importance. Effective (aerosolized antibiotics for ventilator-associated pneumonia) and ineffective (procalcitonin algorithm for antibiotic deescalation) approaches were published. In 2014, several publications raised an important point shared by survivors from sepsis and/or AKI. The increased number of survivors over time brought out long-term sequelae, leading to a poor outcome after hospital discharge. Among them, cardiovascular events and chronic kidney disease may explain the significant increase in the risk of death, which can persist up to 10 years and significantly increases the use of health care. Postdischarge survival represents a new target for future research in sepsis and AKI to find how we can prevent and manage long-term sequelae. A milestone of the year was the Ebola outbreak. The Journal contributed to our better understanding of Ebola virus disease with a paper underlying the crucial role of a large implementation of pragmatic supportive care, including fluid infusion and correction of metabolic abnormalities, to save more lives. PMID:26029837

  3. Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in Critically Ill Patients

    PubMed Central

    Shao, Min; Li, Guangxi; Sarvottam, Kumar; Wang, Shengyu; Thongprayoon, Charat; Dong, Yue; Gajic, Ognjen

    2016-01-01

    Introduction Dyschloremia is common in critically ill patients, although its impact has not been well studied. We investigated the epidemiology of dyschloremia and its associations with the incidence of acute kidney injury and other intensive care unit outcomes. Material and Methods This is a single-center, retrospective cohort study at Mayo Clinic Hospital—Rochester. All adult patients admitted to intensive care units from January 1st, 2006, through December 30th, 2012 were included. Patients with known acute kidney injury and chronic kidney disease stage 5 before intensive care unit admission were excluded. We evaluated the association of dyschloremia with ICU outcomes, after adjustments for the effect of age, gender, Charlson comorbidity index and severity of illness score. Results A total of 6,025 patients were enrolled in the final analysis following the implementation of eligibility criteria. From the cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney injury was higher in hypochloremic and hyperchloremic patients compared to those with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P < .001). Baseline serum chloride was lower in the acute kidney injury group vs. the non-acute kidney injury group [100 mmol/L (96–104) vs. 102 mmol/L (98–105), P < .0001]. In a multivariable logistic regression model, baseline serum chloride of ≤94 mmol/L found to be independently associated with the risk of acute kidney injury (OR 1.7, 95% CI 1.1–2.6; P = .01). Discussion Dyschloremia is common in critically ill patients, and severe hypochloremia is independently associated with an increased risk of development of acute kidney injury. PMID:27490461

  4. Loxosceles gaucho Venom-Induced Acute Kidney Injury – In Vivo and In Vitro Studies

    PubMed Central

    Lucato, Rui V.; Abdulkader, Regina C. R. M.; Barbaro, Katia C.; Mendes, Glória E.; Castro, Isac; Baptista, Maria A. S. F.; Cury, Patrícia M.; Malheiros, Denise M. C.; Schor, Nestor; Yu, Luis; Burdmann, Emmanuel A.

    2011-01-01

    Background Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI). There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. Methodology/Principal Findings In order to test Loxosceles gaucho venom (LV) nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control). LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. Conclusions/Significance Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite. PMID:21655312

  5. Impact of onset time of acute kidney injury on outcomes in patients with acute decompensated heart failure.

    PubMed

    Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei

    2016-01-01

    Since acute kidney injury (AKI) is not always related to mortality in patients with acute decompensated heart failure (ADHF), the aim of this study was to focus on onset time of AKI and its clinical importance. A total of 371 ADHF patients were included. The impact of AKI (≥ 0.3 mg/dl or 1.5-fold increase in serum creatinine level within 48 h) with early onset (≤ 4 days from admission) or late onset (≥ 5 days from admission) was assessed. AKI occurred in 99 patients, who were divided into two groups according to the median onset time of AKI: 50 with early onset of AKI and 49 with late onset of AKI. The maximum increase in serum creatinine level from admission was greater in patients with late onset of AKI than in patients with early onset of AKI (p = 0.012). Patients with late onset of AKI had a higher 12-month mortality rate than that in patients with early onset of AKI (log-rank test, p = 0.014). Late onset of AKI was an independent predictor of mortality (hazard ratio: 3.39, 95 % confidence interval: 1.84-6.18, p < 0.001). Late onset of AKI was associated with high blood urea nitrogen level at admission and intravenous administration of dobutamine. In conclusion, late onset of AKI related to high blood urea nitrogen level and intravenous administration of dobutamine, but not early onset of AKI, is linked to high mortality rate. Onset time of AKI may be useful for risk stratification of mortality in ADHF patients developing AKI.

  6. Effects of acute and chronic hypohydration on kidney health and function.

    PubMed

    Feehally, John; Khosravi, Maryam

    2015-09-01

    The kidneys play a critical role in the homeostasis of body fluid tonicity and effective circulating volume. Renal homeostatic mechanisms are frequently challenged in acutely ill people. Fluid depletion causing hypovolemia may result in renal hypoperfusion that, if left untreated, may lead to acute kidney failure. Some populations, notably older people and neonates, are less tolerant of extremes in fluid loading and deprivation, similar to those with established chronic kidney disease. Risk of kidney injury during fluid depletion is increased by medications including diuretics, nonsteroidal antiinflammatory drugs, and renin-angiotensin system blockers. There is no consistent evidence indicating that lower-than-average fluid intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Increasing consumption of sugar-containing beverages is, however, a major concern for kidney health as a precursor of obesity and diabetes. There is no evidence that high dietary protein intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Idiosyncratic, adverse renal responses have been described with creatine supplements. There are only a few clinical conditions for which high fluid intake should be considered. These include recurrent kidney stones or urinary tract infections and, possibly, polycystic kidney disease. PMID:26290296

  7. Effects of acute and chronic hypohydration on kidney health and function.

    PubMed

    Feehally, John; Khosravi, Maryam

    2015-09-01

    The kidneys play a critical role in the homeostasis of body fluid tonicity and effective circulating volume. Renal homeostatic mechanisms are frequently challenged in acutely ill people. Fluid depletion causing hypovolemia may result in renal hypoperfusion that, if left untreated, may lead to acute kidney failure. Some populations, notably older people and neonates, are less tolerant of extremes in fluid loading and deprivation, similar to those with established chronic kidney disease. Risk of kidney injury during fluid depletion is increased by medications including diuretics, nonsteroidal antiinflammatory drugs, and renin-angiotensin system blockers. There is no consistent evidence indicating that lower-than-average fluid intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Increasing consumption of sugar-containing beverages is, however, a major concern for kidney health as a precursor of obesity and diabetes. There is no evidence that high dietary protein intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Idiosyncratic, adverse renal responses have been described with creatine supplements. There are only a few clinical conditions for which high fluid intake should be considered. These include recurrent kidney stones or urinary tract infections and, possibly, polycystic kidney disease.

  8. Challenges of treating a 466-kilogram man with acute kidney injury.

    PubMed

    Friedman, Allon N; Decker, Brian; Seele, Louis; Hellman, Richard N

    2008-07-01

    Caring for super obese patients (body mass index > 50 kg/m(2)) presents a number of complex and unique clinical challenges, particularly when acute kidney injury is present. We describe our experience treating the heaviest individual with acute kidney injury requiring renal replacement therapy reported to date. A 24-year-old black man was admitted to our hospital with fever, vomiting, progressive weakness, shortness of breath, and hemoptysis. Admission weight was 1,024 lbs (466 kg), height was 6 ft 4 in (1.9 m), and body mass index was 125 kg/m(2). During hospitalization, the patient experienced oligoanuric acute kidney injury and required initiation of continuous and subsequently intermittent renal replacement therapy. This clinical scenario identifies the many challenges involved in caring for super obese patients with acute kidney injury and may be a harbinger of what awaits the nephrology community in the obesity pandemic era.

  9. Effect of acute and chronic hypernatremia on myoinositol and sorbitol concentration in rat brain and kidney.

    PubMed

    Lohr, J W; McReynolds, J; Grimaldi, T; Acara, M

    1988-01-01

    In animal models of hypernatremia, increases in brain electrolyte content account for the entire increase in osmolality in acute but not chronic hypernatremia, suggesting that there is generation of additional intracellular solutes ("idiogenic osmoles") in chronic hypernatremic states. In the present study, the concentration of the polyols myoinositol and sorbitol and water content were determined in the brain and kidneys of rats made acutely (2 hours) and chronically (72 hours) hypernatremic by intraperitoneal injection of NaCl and water restriction. Both the brain and the kidney responded to chronic hypernatremia with increased levels of myoinositol. Sorbitol levels increased in the kidney in response to both acute and chronic hypernatremia. Water content dropped in acute hypernatremia, but remained unchanged during chronic hyperosmolar challenge. We conclude that the polyols, myoinositol and sorbitol, may play a significant role in cellular osmoregulation in brain and kidney during chronic hypernatremia in the rat.

  10. Single cell dissection of early kidney development: multilineage priming.

    PubMed

    Brunskill, Eric W; Park, Joo-Seop; Chung, Eunah; Chen, Feng; Magella, Bliss; Potter, S Steven

    2014-08-01

    We used a single cell RNA-seq strategy to create an atlas of gene expression patterns in the developing kidney. At several stages of kidney development, histologically uniform populations of cells give rise to multiple distinct lineages. We performed single cell RNA-seq analysis of total mouse kidneys at E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of progenitor cell induction driven primarily by gene repression. Surprising stochastic expression of marker genes associated with differentiated cell types was observed in E11.5 progenitors. We provide a global view of the polarized gene expression already present in the renal vesicle, the first epithelial precursor of the nephron. We show that Hox gene read-through transcripts can be spliced to produce intergenic homeobox swaps. We also identify a surprising number of genes with partially degraded noncoding RNA. Perhaps most interesting, at early developmental times single cells often expressed genes related to several developmental pathways. This provides powerful evidence that initial organogenesis involves a process of multilineage priming. This is followed by a combination of gene repression, which turns off the genes associated with most possible lineages, and the activation of increasing numbers of genes driving the chosen developmental direction. PMID:25053437

  11. Single cell dissection of early kidney development: multilineage priming

    PubMed Central

    Brunskill, Eric W.; Park, Joo-Seop; Chung, Eunah; Chen, Feng; Magella, Bliss; Potter, S. Steven

    2014-01-01

    We used a single cell RNA-seq strategy to create an atlas of gene expression patterns in the developing kidney. At several stages of kidney development, histologically uniform populations of cells give rise to multiple distinct lineages. We performed single cell RNA-seq analysis of total mouse kidneys at E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of progenitor cell induction driven primarily by gene repression. Surprising stochastic expression of marker genes associated with differentiated cell types was observed in E11.5 progenitors. We provide a global view of the polarized gene expression already present in the renal vesicle, the first epithelial precursor of the nephron. We show that Hox gene read-through transcripts can be spliced to produce intergenic homeobox swaps. We also identify a surprising number of genes with partially degraded noncoding RNA. Perhaps most interesting, at early developmental times single cells often expressed genes related to several developmental pathways. This provides powerful evidence that initial organogenesis involves a process of multilineage priming. This is followed by a combination of gene repression, which turns off the genes associated with most possible lineages, and the activation of increasing numbers of genes driving the chosen developmental direction. PMID:25053437

  12. Selective depletion of mouse kidney proximal straight tubule cells causes acute kidney injury.

    PubMed

    Sekine, Michiko; Monkawa, Toshiaki; Morizane, Ryuji; Matsuoka, Kunie; Taya, Choji; Akita, Yoshiko; Joh, Kensuke; Itoh, Hiroshi; Hayashi, Matsuhiko; Kikkawa, Yoshiaki; Kohno, Kenji; Suzuki, Akemi; Yonekawa, Hiromichi

    2012-02-01

    The proximal straight tubule (S3 segment) of the kidney is highly susceptible to ischemia and toxic insults but has a remarkable capacity to repair its structure and function. In response to such injuries, complex processes take place to regenerate the epithelial cells of the S3 segment; however, the precise molecular mechanisms of this regeneration are still being investigated. By applying the "toxin receptor mediated cell knockout" method under the control of the S3 segment-specific promoter/enhancer, Gsl5, which drives core 2 β-1,6-N-acetylglucosaminyltransferase gene expression, we established a transgenic mouse line expressing the human diphtheria toxin (DT) receptor only in the S3 segment. The administration of DT to these transgenic mice caused the selective ablation of S3 segment cells in a dose-dependent manner, and transgenic mice exhibited polyuria containing serum albumin and subsequently developed oliguria. An increase in the concentration of blood urea nitrogen was also observed, and the peak BUN levels occurred 3-7 days after DT administration. Histological analysis revealed that the most severe injury occurred in the S3 segments of the proximal tubule, in which tubular cells were exfoliated into the tubular lumen. In addition, aquaporin 7, which is localized exclusively to the S3 segment, was diminished. These results indicate that this transgenic mouse can suffer acute kidney injury (AKI) caused by S3 segment-specific damage after DT administration. This transgenic line offers an excellent model to uncover the mechanisms of AKI and its rapid recovery.

  13. A Clinical Study of Acute Kidney Injury in Tropical Acute Febrile Illness

    PubMed Central

    Bhat, Ajay; Prabhu, Mangalore Venkatraya

    2016-01-01

    Introduction Tropical Acute Febrile Illness (TAFI) is one of the most common causes of morbidity within the community. Acute Kidney Injury (AKI) due to infective and non infective causes is a major complication. Presence of AKI is a major cause of mortality among patients with TAFI. Aim To study the spectrum of tropical acute febrile illness; the proportion, spectrum and staging of acute kidney injury; Renal Replacement Therapy (RRT) initiation and in-hospital mortality. Materials and Methods A total of 600 TAFI patients were prospectively studied at a tertiary care centre in coastal Karnataka between September 2012 and September 2014 for the aetiology of TAFI; the development and staging of AKI based on Kidney disease: Improving global outcomes (KDIGO) guidelines; the initiation of RRT and in-hospital mortality. Statistical Analysis: Data analysis was done using SPSS version 17.0 with statistical significance calculated using chi-square and Fisher’s exact t-test for which p-value <0.05 was considered significant. Results The spectrum of TAFI, in decreasing order, was vivax malaria, leptospirosis, dengue fever, falciparum malaria, mixed malaria, enteric fever, scrub typhus and the most common aetiology was malaria. The proportion of AKI was 54%. The most common cause of AKI, its stages 2 and 3, RRT initiation and in-hospital mortality was leptospirosis; and AKI stage 1 was dengue fever. KDIGO AKI stage 1, 2 and 3 was seen in 46.9%, 31.2% and 21.9% of AKI patients, respectively. RRT initiation was required in 10.2% of AKI patients and in-hospital mortality was 3% among all patients. AKI, RRT initiationand in-hospital mortality were significantly associated with older age, fever duration and other presenting complaints, examination findings, renal function and other parameters, leptospirosis, dengue fever, falciparum malaria. Conclusion The aetiology in about half of TAFI patients in coastal Karnataka was malaria. More than 50% develop AKI with greater than one

  14. Early-life course socioeconomic factors and chronic kidney disease.

    PubMed

    Brophy, Patrick D; Shoham, David A; Charlton, Jennifer R; Carmody, J Bryan; Reidy, Kimberly J; Harshman, Lyndsay; Segar, Jeffrey; Askenazi, David

    2015-01-01

    Kidney failure or ESRD affects approximately 650,000 Americans, whereas the number with earlier stages of CKD is much higher. Although CKD and ESRD are usually associated with adulthood, it is likely that the initial stages of CKD begin early in life. Many of these pathways are associated with low birth weight and disadvantaged socioeconomic status (SES) in childhood, translating childhood risk into later-life CKD and kidney failure. Social factors are thought to be fundamental causes of disease. Although the relationship between adult SES and CKD has been well established, the role of early childhood SES for CKD risk remains obscure. This review provides a rationale for examining the association between early-life SES and CKD. By collecting data on early-life SES and CKD, the interaction with other periods in the life course could also be studied, allowing for examination of whether SES trajectories (eg, poverty followed by affluence) or cumulative burden (eg, poverty at multiple time points) are more relevant to lifetime CKD risk.

  15. Paneth cell-mediated multiorgan dysfunction after acute kidney injury

    PubMed Central

    Park, Sang Won; Kim, Mihwa; Kim, Joo Yun; Ham, Ahrom; Brown, Kevin M.; Mori-Akiyama, Yuko; Ouellette, André J.; D’Agati, Vivette D.; Lee, H. Thomas

    2012-01-01

    Acute kidney injury (AKI) is frequently complicated by extra-renal multi-organ injury including intestinal and hepatic dysfunction. In this study, we hypothesized that a discrete intestinal source of pro-inflammatory mediators drives multi-organ injury in response to AKI. After induction of AKI in mice by renal ischemia-reperfusion or bilateral nephrectomy, small intestinal Paneth cells increased the synthesis and release of IL-17A in conjunction with severe intestinal apoptosis and inflammation. We also detected significantly increased IL-17A in portal and systemic circulation after AKI. Intestinal macrophages appear to transport released Paneth cell granule constituents induced by AKI, away from the base of the crypts into the liver. Genetic or pharmacologic depletion of Paneth cells decreased small intestinal IL-17A secretion and plasma IL-17A levels significantly and attenuated intestinal, hepatic, and renal injury after AKI. Similarly, portal delivery of IL-17A in macrophage depleted mice decreased markedly, and intestinal, hepatic, and renal injury following AKI was attenuated without affecting intestinal IL-17A generation. In conclusion, AKI induces IL-17A synthesis and secretion by Paneth cells to initiate intestinal and hepatic injury by hepatic and systemic delivery of IL-17A by macrophages. Modulation of Paneth cell dysregulation may have therapeutic implications by reducing systemic complications arising from AKI. PMID:23109723

  16. Enabling innovative translational research in acute kidney injury

    PubMed Central

    Zarjou, Abolfazl; Sanders, Paul W; Mehta, Ravindra L; Agarwal, Anupam

    2011-01-01

    Acute kidney injury (AKI) is a common, heterogeneous and detrimental clinical condition that has significant attributable morbidity and mortality. Despite major advances in understanding the epidemiology, pathogenesis and outcomes of AKI, preventive measures remain inadequate and therapeutic approaches (except for renal replacement therapy) have largely proven futile so far. Critical to the process of designing rational therapies is translational research, which involves the transition between the basic research discoveries and everyday clinical applications to prevent, diagnose and treat human diseases. Progress in innovative approaches has been hampered due in part to the reliance on functional markers (serum creatinine and blood urea nitrogen) that are neither sensitive nor specific to diagnose AKI. This limitation has created a great deal of interest and intense investigation to identify a “troponin-like marker” that would facilitate recognition of AKI and allow for timely implementation of the precise therapeutic agent. The other major obstacle in this field is the diverse and complex nature of AKI that involves multiple independent and overlapping pathways, making it difficult to cure AKI with a single approach. In this review, we will summarize the advances, ongoing studies and future perspectives in the field of translational research of AKI. PMID:22376265

  17. Bath salt intoxication causing acute kidney injury requiring hemodialysis.

    PubMed

    Regunath, Hariharan; Ariyamuthu, Venkatesh Kumar; Dalal, Pranavkumar; Misra, Madhukar

    2012-10-01

    Traditional bath salts contain a combination of inorganic salts like Epsom salts, table salt, baking soda, sodium metaphosphate, and borax that have cleansing properties. Since 2010, there have been rising concerns about a new type of substance abuse in the name of "bath salts." They are beta-ketone amphetamine analogs and are derivates of cathinone, a naturally occurring amphetamine analog found in the "khat" plant (Catha edulis). Effects reported with intake included increased energy, empathy, openness, and increased libido. Serious adverse effects reported with intoxication included cardiac, psychiatric, and neurological signs and symptoms. Not much is known about the toxicology and metabolism of these compounds. They inhibit monoamine reuptake (dopamine, nor epinephrine, etc.) and act as central nervous system stimulants with high additive and abuse potential because of their clinical and biochemical similarities to effects from use of cocaine, amphetamine, and 3,4-methylenedioxy-N-methylamphetamine. Deaths associated with use of these compounds have also been reported. We report a case of acute kidney injury associated with the use of "bath salt" pills that improved with hemodialysis. PMID:23036036

  18. Clinical Predictors of Acute Kidney Injury Following Snake Bite Envenomation

    PubMed Central

    Dharod, Mrudul V; Patil, Tushar B; Deshpande, Archana S; Gulhane, Ragini V; Patil, Mangesh B; Bansod, Yogendra V

    2013-01-01

    Background: Snake bite envenomation is a major public health concern in developing countries. Acute kidney injury (AKI) is as important cause of mortality in patients with vasculotoxic snake bite. Aims: This study was to evaluate the clinical profile of snake bite patients and to determine the predictors of developing AKI following snake bite. Materials and Methods: Two hundred and eighty-one patients with snake envenomation were included. Eighty-seven patients developed AKI (Group A) and 194 (Group B) did not. History, examination findings and investigations results were recorded and compared between the two groups. Results: In group A, 61 (70.11%) patients were male and in group B, 117 (60.30%) patients were male. Out of 281 patients, 232 had cellulitis, 113 had bleeding tendencies, 87 had oliguria, 76 had neuroparalysis, and 23 had hypotension at presentation. After multivariate analysis, bite to hospital time (P = 0.016), hypotension (P = 0.000), albuminuria (P = 0.000), bleeding time (P = 0.000), prothrombin time (P = 0.000), hemoglobin (P = 0.000) and total bilirubin (P = 0.010) were significant independent predictors of AKI. Conclusions: AKI developed in 30.96% of patients with snake bite, leading to mortality in 39.08% patients. Factors associated with AKI are bite to hospital time, hypotension, albuminuria, prolonged bleeding time, prolonged prothrombin time, low hemoglobin and a high total bilirubin. PMID:24350071

  19. Organophosphate Poisoning and Subsequent Acute Kidney Injury Risk

    PubMed Central

    Lee, Feng-You; Chen, Wei-Kung; Lin, Cheng-Li; Lai, Ching-Yuan; Wu, Yung-Shun; Lin, I-Ching; Kao, Chia-Hung

    2015-01-01

    Abstract Small numbers of the papers have studied the association between organophosphate (OP) poisoning and the subsequent acute kidney injury (AKI). Therefore, we used the National Health Insurance Research Database (NHIRD) to study whether patients with OP poisoning are associated with a higher risk to have subsequent AKI. The retrospective cohort study comprised patients aged ≥20 years with OP poisoning and hospitalized diagnosis during 2000–2011 (N = 8924). Each OP poisoning patient was frequency-matched to 4 control patients based on age, sex, index year, and comorbidities of diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, coronary artery disease, and stroke (N = 35,696). We conducted Cox proportional hazard regression analysis to estimate the effects of OP poisoning on AKI risk. The overall incidence of AKI was higher in the patients with OP poisoning than in the controls (4.85 vs 3.47/1000 person-years). After adjustment for age, sex, comorbidity, and interaction terms, patients with OP poisoning were associated with a 6.17-fold higher risk of AKI compared with the comparison cohort. Patients with highly severe OP poisoning were associated with a substantially increased risk of AKI. The study found OP poisoning is associated with increased risk of subsequent AKI. Future studies are encouraged to evaluate whether long-term effects exist and the best guideline to prevent the continuously impaired renal function. PMID:26632728

  20. Bath salt intoxication causing acute kidney injury requiring hemodialysis.

    PubMed

    Regunath, Hariharan; Ariyamuthu, Venkatesh Kumar; Dalal, Pranavkumar; Misra, Madhukar

    2012-10-01

    Traditional bath salts contain a combination of inorganic salts like Epsom salts, table salt, baking soda, sodium metaphosphate, and borax that have cleansing properties. Since 2010, there have been rising concerns about a new type of substance abuse in the name of "bath salts." They are beta-ketone amphetamine analogs and are derivates of cathinone, a naturally occurring amphetamine analog found in the "khat" plant (Catha edulis). Effects reported with intake included increased energy, empathy, openness, and increased libido. Serious adverse effects reported with intoxication included cardiac, psychiatric, and neurological signs and symptoms. Not much is known about the toxicology and metabolism of these compounds. They inhibit monoamine reuptake (dopamine, nor epinephrine, etc.) and act as central nervous system stimulants with high additive and abuse potential because of their clinical and biochemical similarities to effects from use of cocaine, amphetamine, and 3,4-methylenedioxy-N-methylamphetamine. Deaths associated with use of these compounds have also been reported. We report a case of acute kidney injury associated with the use of "bath salt" pills that improved with hemodialysis.

  1. Hospital Mortality in the United States following Acute Kidney Injury

    PubMed Central

    Rezaee, Michael E.; Marshall, Emily J.; Matheny, Michael E.

    2016-01-01

    Acute kidney injury (AKI) is a common reason for hospital admission and complication of many inpatient procedures. The temporal incidence of AKI and the association of AKI admissions with in-hospital mortality are a growing problem in the world today. In this review, we discuss the epidemiology of AKI and its association with in-hospital mortality in the United States. AKI has been growing at a rate of 14% per year since 2001. However, the in-hospital mortality associated with AKI has been on the decline starting with 21.9% in 2001 to 9.1 in 2011, even though the number of AKI-related in-hospital deaths increased almost twofold from 147,943 to 285,768 deaths. We discuss the importance of the 71% reduction in AKI-related mortality among hospitalized patients in the United States and draw on the discussion of whether or not this is a phenomenon of hospital billing (coding) or improvements to the management of AKI. PMID:27376083

  2. Sepsis-induced acute kidney injury in patients with cirrhosis.

    PubMed

    Angeli, Paolo; Tonon, Marta; Pilutti, Chiara; Morando, Filippo; Piano, Salvatore

    2016-01-01

    Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.

  3. Wnt4 is a novel biomarker for the early detection of kidney tubular injury after ischemia/reperfusion injury.

    PubMed

    Zhao, Shi-Lei; Wei, Shi-Yao; Wang, Yu-Xiao; Diao, Tian-Tian; Li, Jian-Si; He, Yi-Xin; Yu, Jing; Jiang, Xi-Yue; Cao, Yang; Mao, Xin-Yue; Wei, Qiu-Ju; Wang, Yu; Li, Bing

    2016-01-01

    Earlier intervention after acute kidney injury would promote better outcomes. Our previous study found that Wnt proteins are promptly upregulated after ischemic kidney injury. Thus, we assessed whether Wnt4 could be an early and sensitive biomarker of tubular injury. We subjected mice to bilateral ischemia/reperfusion injury (IRI). Kidney and urinary Wnt4 expression showed an early increase at 3 hours and increased further at 24 hours post-IRI and was closely correlated with histopathological alterations. Serum creatinine slightly increased at 6 hours, indicating that it was less sensitive than Wnt4 expression. These data were further confirmed by clinical study. Both kidney and urinary Wnt4 expression were significantly increased in patients diagnosed with biopsy-proven minimal change disease (MCD) with tubular injury, all of whom nevertheless had normal estimated glomerular filtration rate (eGFR) and serum creatinine. The increased Wnt4 expression also strongly correlated with histopathological alterations in these MCD patients. In conclusion, this is the first demonstration that increases in both kidney and urinary Wnt4 expression can be detected more sensitively and earlier than serum creatinine after kidney injury. In particular, urinary Wnt4 could be a potential noninvasive biomarker for the early detection of tubular injury. PMID:27600466

  4. Wnt4 is a novel biomarker for the early detection of kidney tubular injury after ischemia/reperfusion injury

    PubMed Central

    Zhao, Shi-Lei; Wei, Shi-Yao; Wang, Yu-Xiao; Diao, Tian-Tian; Li, Jian-Si; He, Yi-Xin; Yu, Jing; Jiang, Xi-Yue; Cao, Yang; Mao, Xin-Yue; Wei, Qiu-Ju; Wang, Yu; Li, Bing

    2016-01-01

    Earlier intervention after acute kidney injury would promote better outcomes. Our previous study found that Wnt proteins are promptly upregulated after ischemic kidney injury. Thus, we assessed whether Wnt4 could be an early and sensitive biomarker of tubular injury. We subjected mice to bilateral ischemia/reperfusion injury (IRI). Kidney and urinary Wnt4 expression showed an early increase at 3 hours and increased further at 24 hours post-IRI and was closely correlated with histopathological alterations. Serum creatinine slightly increased at 6 hours, indicating that it was less sensitive than Wnt4 expression. These data were further confirmed by clinical study. Both kidney and urinary Wnt4 expression were significantly increased in patients diagnosed with biopsy-proven minimal change disease (MCD) with tubular injury, all of whom nevertheless had normal estimated glomerular filtration rate (eGFR) and serum creatinine. The increased Wnt4 expression also strongly correlated with histopathological alterations in these MCD patients. In conclusion, this is the first demonstration that increases in both kidney and urinary Wnt4 expression can be detected more sensitively and earlier than serum creatinine after kidney injury. In particular, urinary Wnt4 could be a potential noninvasive biomarker for the early detection of tubular injury. PMID:27600466

  5. Wnt4 is a novel biomarker for the early detection of kidney tubular injury after ischemia/reperfusion injury.

    PubMed

    Zhao, Shi-Lei; Wei, Shi-Yao; Wang, Yu-Xiao; Diao, Tian-Tian; Li, Jian-Si; He, Yi-Xin; Yu, Jing; Jiang, Xi-Yue; Cao, Yang; Mao, Xin-Yue; Wei, Qiu-Ju; Wang, Yu; Li, Bing

    2016-01-01

    Earlier intervention after acute kidney injury would promote better outcomes. Our previous study found that Wnt proteins are promptly upregulated after ischemic kidney injury. Thus, we assessed whether Wnt4 could be an early and sensitive biomarker of tubular injury. We subjected mice to bilateral ischemia/reperfusion injury (IRI). Kidney and urinary Wnt4 expression showed an early increase at 3 hours and increased further at 24 hours post-IRI and was closely correlated with histopathological alterations. Serum creatinine slightly increased at 6 hours, indicating that it was less sensitive than Wnt4 expression. These data were further confirmed by clinical study. Both kidney and urinary Wnt4 expression were significantly increased in patients diagnosed with biopsy-proven minimal change disease (MCD) with tubular injury, all of whom nevertheless had normal estimated glomerular filtration rate (eGFR) and serum creatinine. The increased Wnt4 expression also strongly correlated with histopathological alterations in these MCD patients. In conclusion, this is the first demonstration that increases in both kidney and urinary Wnt4 expression can be detected more sensitively and earlier than serum creatinine after kidney injury. In particular, urinary Wnt4 could be a potential noninvasive biomarker for the early detection of tubular injury.

  6. Failure to visualize acutely injured kidneys with technetium-99m DMSA does not preclude recoverable function

    SciTech Connect

    Taylor, A. Jr.; Akiya, F.; Gregory, M.C.

    1986-03-01

    A 35-yr-old patient developed severe acute tubular necrosis requiring hemodialysis. A (99mTc)dimercaptosuccinic acid scan of the kidneys showed no renal uptake at 4 or 24 hr, but the patient subsequently recovered normal renal function as judged by a normal serum creatinine. Based on this case report and a review of the literature, one cannot assume irreversible loss of function in patients with acute renal failure, based on the absence of radiopharmaceutical uptake by the kidneys.

  7. Significant Racial Differences in the Key Factors Associated with Early Graft Loss in Kidney Transplant Recipients

    PubMed Central

    Taber, David J; Douglass, Kevin; Srinivas, Titte; McGillicuddy, John W; Bratton, Charles F; Chavin, Kenneth D; Baliga, Prabhakar K; Egede, Leonard E

    2014-01-01

    Background There is continued and significant debate regarding the salient etiologies associated with graft loss and racial disparities in kidney transplant (KTX) recipients. Methods This was a longitudinal cohort study of all adult KTX recipients, comparing patients with early graft loss (<5 yrs) to those with graft longevity (surviving graft with at least 5 yrs of follow-up) across racial cohorts (African-American (AA) and non-AA) to discern risk factors. Results 524 patients were included, 55% AA, 151 with early graft loss (29%) and 373 with graft longevity (71%). Consistent within both races, early graft loss was significantly associated with disability income (adjusted odds-ratio [AOR] 2.2, 95% CI: 1.1-4.5), kidney donor risk index (AOR 3.2, 1.4-7.5), rehospitalization (AOR 2.1, 1.0-4.4) and acute rejection (AOR 4.4, 1.7-11.6) Unique risk factors in AAs included Medicare only insurance (AOR 8.0, 2.3-28) and BK infectio (AOR 5.6, 1.3-25). Unique protective factors in AAs included cardiovascular risk factor control: AAs with a mean systolic BP <150 mmHg had 80% lower risk of early graft loss (AOR 0.2, 0.1-0.7), while LDL <100 mg/dL (AOR 0.4, 0.2-0.8), triglycerides <150 mg/dL (AOR 0.4, 0.2-1.0) and HgbA1C <7% (AOR 0.2, 0.1-0.6) were also protective against early graft loss in AA, but no in non-AA recipients. Conclusions AA recipients have a number of unique risk factors for early graft loss, suggesting that controlling cardiovascular comorbidities may be an important mechanism to reduce racial disparities in kidney transplantation. PMID:24969370

  8. Effects of acute sodium fluoride exposure on kidney function, water homeostasis, and renal handling of calcium and inorganic phosphate.

    PubMed

    Santoyo-Sanchez, Mitzi Paola; del Carmen Silva-Lucero, Maria; Arreola-Mendoza, Laura; Barbier, Olivier Christophe

    2013-06-01

    Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver and kidney. In this study, we performed an early analysis of renal function using a clearance technique in Wistar rats acutely exposed to fluoride at a plasma concentration of 0.625 μg/ml. Our results revealed that fluoride, at a concentration close to the concentration present in the serum after environmental exposure, induced a significant tubular dysfunction, resulting in diluted urine, impaired protein reabsorption, and increased calcium and phosphate urinary excretion. Our work demonstrates that even acute exposures to low concentrations of NaF may induce renal damage and confirms that, after exposure, the kidney participates directly in the calcium and phosphate deficiencies observed in fluoride-exposed populations.

  9. [Acute Kidney Injury, Type - 3 cardiorenal syndrome, Biomarkers, Renal Replacement Therapy].

    PubMed

    Di Lullo, Luca; Bellasi, Antonio; Barbera, Vincenzo; Cozzolino, Mario; Russo, Domenico; De Pascalis, Antonio; Santoboni, Francesca; Villani, Annalisa; De Rosa, Silvia; Colafelice, Marco; Russo, Luigi; Ronco, Claudio

    2016-01-01

    Cardiovascular disease and major cardiovascular events represent main cause of death in both acute and chronic kidney disease patients. Kidney and heart failure are common and frequently co-exist This organ-organ interaction, also called organ cross-talk, leads to well-known definition of cardiorenal syndrome (CRS). Here we will describe cardiovascular involvement in patients with acute kidney injury (AKI). Also known as Type-3 CRS or acute reno-cardiac CRS, it occurs when AKI contributes and/or precipitates development of acute cardiac injury. AKI may directly or indirectly produces an acute cardiac event and it can be associated with volume overload, metabolic acidosis and electrolytes disorders such as hyperkalemia and hypocalcemia, coronary artery disease, left ventricular dysfunction and fibrosis which has been also described in patients with AKI with the consequence of direct negative effects on cardiac performance. PMID:27374388

  10. Community-acquired acute kidney injury: A challenge and opportunity for primary care in kidney health.

    PubMed

    Mesropian, Paul Der; Othersen, Jennifer; Mason, Darius; Wang, Jeffrey; Asif, Arif; Mathew, Roy O

    2016-09-01

    Community-acquired acute kidney injury (CA-AKI) has been found to be a common event in the population. Current incidence estimates are not available, but evaluations of severe elevations in serum creatinine indicate that incidence can be as high as 989 cases per million population in those older than 80 years. Data on risk factors are limited, but older age and higher comorbid illness burden, especially diabetes and cardiovascular disease, seem to be more common in patients who suffer CA-AKI. In addition to being more common than hospital-acquired AKI, the long-term sequelae of CA-AKI seem to be just as severe, including renal disease progression and mortality. Efforts to better understand the aetiology of CA-AKI and how ultimately to prevent the development of this condition will need to be taken. In the meantime, a concerted effort by general internists and nephrologists will be needed to prevent CA-AKI in the highest risk patients and thus limit the poor outcomes associated with this entity. PMID:26890822

  11. Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes.

    PubMed

    Sabbisetti, Venkata S; Waikar, Sushrut S; Antoine, Daniel J; Smiles, Adam; Wang, Chang; Ravisankar, Abinaya; Ito, Kazumi; Sharma, Sahil; Ramadesikan, Swetha; Lee, Michelle; Briskin, Rebeccah; De Jager, Philip L; Ngo, Thanh Thu; Radlinski, Mark; Dear, James W; Park, Kevin B; Betensky, Rebecca; Krolewski, Andrzej S; Bonventre, Joseph V

    2014-10-01

    Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.

  12. Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.

    PubMed

    Choi, Iee Ho; Hwang, Pyoung Han; Choi, Sam Im; Lee, Dae Yeol; Kim, Min Sun

    2016-09-01

    Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas. PMID:27510397

  13. Cardiac Biomarkers and Acute Kidney Injury After Cardiac Surgery

    PubMed Central

    Bucholz, Emily M.; Whitlock, Richard P.; Zappitelli, Michael; Devarajan, Prasad; Eikelboom, John; Garg, Amit X.; Philbrook, Heather Thiessen; Devereaux, Philip J.; Krawczeski, Catherine D.; Kavsak, Peter; Shortt, Colleen

    2015-01-01

    OBJECTIVES: To examine the relationship of cardiac biomarkers with postoperative acute kidney injury (AKI) among pediatric patients undergoing cardiac surgery. METHODS: Data from TRIBE-AKI, a prospective study of children undergoing cardiac surgery, were used to examine the association of cardiac biomarkers (N-type pro–B-type natriuretic peptide, creatine kinase-MB [CK-MB], heart-type fatty acid binding protein [h-FABP], and troponins I and T) with the development of postoperative AKI. Cardiac biomarkers were collected before and 0 to 6 hours after surgery. AKI was defined as a ≥50% or 0.3 mg/dL increase in serum creatinine, within 7 days of surgery. RESULTS: Of the 106 patients included in this study, 55 (52%) developed AKI after cardiac surgery. Patients who developed AKI had higher median levels of pre- and postoperative cardiac biomarkers compared with patients without AKI (all P < .01). Preoperatively, higher levels of CK-MB and h-FABP were associated with increased odds of developing AKI (CK-MB: adjusted odds ratio 4.58, 95% confidence interval [CI] 1.56–13.41; h-FABP: adjusted odds ratio 2.76, 95% CI 1.27–6.03). When combined with clinical models, both preoperative CK-MB and h-FABP provided good discrimination (area under the curve 0.77, 95% CI 0.68–0.87, and 0.78, 95% CI 0.68–0.87, respectively) and improved reclassification indices. Cardiac biomarkers collected postoperatively did not significantly improve the prediction of AKI beyond clinical models. CONCLUSIONS: Preoperative CK-MB and h-FABP are associated with increased risk of postoperative AKI and provide good discrimination of patients who develop AKI. These biomarkers may be useful for risk stratifying patients undergoing cardiac surgery. PMID:25755241

  14. Postpartum acute kidney injury: a review of 99 cases.

    PubMed

    Eswarappa, Mahesh; Madhyastha, P Rakesh; Puri, Sonika; Varma, Vijay; Bhandari, Aneesh; Chennabassappa, Gurudev

    2016-07-01

    Postpartum acute kidney injury (PPAKI) constitutes an important cause of obstetric AKI. It is associated with high maternal and fetal mortality in developing nations. The aim of this study is to survey the etiology and outcomes of PPAKI in a tertiary care Indian hospital. Ninety-nine patients, without prior comorbidities, treated for PPAKI, between 2005-2014 at M.S. Ramaiah Medical College, were included for analysis in this retrospective, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per RIFLE criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal and fetal outcomes. PPAKI constituted 60% of all obstetric AKI cases. Median maternal age was 23 years and 52% of patients were primigravidas. Mean serum creatinine was 4.1 mg/dL. Failure (33%) and injury (31%) were the major categories as per RIFLE criteria. Thirty-nine percent of cases required RRT. Sepsis, particularly puerperal sepsis, was the leading causes of PPAKI (75% of cases) and maternal mortality (94% of deaths). Maternal and fetal mortality were 19% and 22% respectively. The incidence of cortical necrosis was 10.3%. Three patients required long-term RRT. In conclusion, consistent with other Indian literature, we report a high incidence of PPAKI. We found incremental mortality on moving from "Risk" to "Failure" category of RIFLE. PPAKI was associated with high maternal and fetal mortality with sepsis being the leading cause. Our study highlights the need for provision of better quality of maternal care and fetal monitoring to decrease mortality associated with PPAKI in developing countries. PMID:27319810

  15. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease.

    PubMed

    Miranda-Díaz, Alejandra Guillermina; Pazarín-Villaseñor, Leonardo; Yanowsky-Escatell, Francisco Gerardo; Andrade-Sierra, Jorge

    2016-01-01

    The increase in the prevalence of diabetes mellitus (DM) and the secondary kidney damage produces diabetic nephropathy (DN). Early nephropathy is defined as the presence of microalbuminuria (30-300 mg/day), including normal glomerular filtration rate (GFR) or a mildly decreased GFR (60-89 mL/min/1.73 m(2)), with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is <30 mg/day. Albuminuria represents the excretion of >300 mg/day. Chronic kidney disease (CKD) is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs) with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β), producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS). The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase). The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health. PMID:27525285

  16. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

    PubMed Central

    Andrade-Sierra, Jorge

    2016-01-01

    The increase in the prevalence of diabetes mellitus (DM) and the secondary kidney damage produces diabetic nephropathy (DN). Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day), including normal glomerular filtration rate (GFR) or a mildly decreased GFR (60–89 mL/min/1.73 m2), with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is <30 mg/day. Albuminuria represents the excretion of >300 mg/day. Chronic kidney disease (CKD) is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs) with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β), producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS). The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase). The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health. PMID:27525285

  17. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients.

    PubMed

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-03-01

    Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages.Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I.Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = -0.76, BUN: r = -0.72, and cystatin C: r = -0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603-0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746-0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P = 0.811, and e

  18. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

    PubMed Central

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-01-01

    Abstract Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages. Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I. Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = −0.76, BUN: r = −0.72, and cystatin C: r = −0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603–0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746–0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P

  19. The Role of Eugenol in the Prevention of Acute Pancreatitis-Induced Acute Kidney Injury: Experimental Study

    PubMed Central

    Markakis, Charalampos; Tsaroucha, Alexandra; Papalois, Apostolos E.; Lambropoulou, Maria; Spartalis, Eleftherios; Tsigalou, Christina; Romanidis, Konstantinos; Simopoulos, Constantinos

    2016-01-01

    Aim. Acute pancreatitis is an inflammatory intra-abdominal disease, which takes a severe form in 15–20% of patients and can result in high mortality especially when complicated by acute renal failure. The aim of this study is to assess the possible reduction in the extent of acute kidney injury after administration of eugenol in an experimental model of acute pancreatitis. Materials and Methods. 106 male Wistar rats weighing 220–350 g were divided into 3 groups: (1) Sham, with sham surgery; (2) Control, with induction of acute pancreatitis, through ligation of the biliopancreatic duct; and (3) Eugenol, with induction of acute pancreatitis and eugenol administration at a dose of 15 mg/kg. Serum urea and creatinine, histopathological changes, TNF-α, IL-6, and MPO activity in the kidneys were evaluated at predetermined time intervals. Results. The group that was administered eugenol showed milder histopathological changes than the Control group, TNF-α activity was milder in the Eugenol group, and there was no difference in activity for MPO and IL-6. Serum urea and creatinine levels were lower in the Eugenol group than in the Control group. Conclusions. Eugenol administration was protective for the kidneys in an experimental model of acute pancreatitis in rats. PMID:26884642

  20. Raising Awareness of Acute Kidney Injury: A Global Perspective of a Silent Killer

    PubMed Central

    Lewington, Andrew JP; Cerdá, Jorge; Mehta, Ravindra L

    2013-01-01

    Worldwide, acute kidney injury (AKI) is associated with poor patient outcomes. Over the last few years, collaborative efforts, enabled by a common definition of AKI, have provided a description of the epidemiology, natural history and outcomes of this disease and improved our understanding of the pathophysiology. There is increased recognition that AKI is encountered in multiple settings and in all age groups, and that its course and outcomes are influenced by the severity and duration of the event. The effect of AKI on an individual patient and the resulting societal burden that ensues from the long term effects of the disease, including development of chronic kidney disease (CKD) and end stage renal disease (ESRD), is attracting increasing scrutiny. There is evidence of marked variation in the management of AKI which is, to a large extent, due to a lack of awareness and an absence of standards for prevention, early recognition and intervention. These emerging data point to an urgent need for a global effort to highlight that AKI is preventable, its course modifiable, and its treatment can improve outcomes. In this article, we provide a framework of reference and propose specific strategies to raise awareness of AKI globally, with the goal to ultimately improve outcomes from this devastating disease. PMID:23636171

  1. Cell-cycle arrest and acute kidney injury: the light and the dark sides

    PubMed Central

    Kellum, John A.; Chawla, Lakhmir S.

    2016-01-01

    Acute kidney injury (AKI) is a common consequence of systemic illness or injury and it complicates several forms of major surgery. Two major difficulties have hampered progress in AKI research and clinical management. AKI is difficult to detect early and its pathogenesis is still poorly understood. We recently reported results from multi-center studies where two urinary markers of cell-cycle arrest, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were validated for development of AKI well ahead of clinical manifestations—azotemia and oliguria. Cell-cycle arrest is known to be involved in the pathogenesis of AKI and this ‘dark side’ may also involve progression to chronic kidney disease. However, cell-cycle arrest has a ‘light side’ as well, since this mechanism can protect cells from the disastrous consequences of entering cell division with damaged DNA or insufficient bioenergetic resources during injury or stress. Whether we can use the light side to help prevent AKI remains to be seen, but there is already evidence that cell-cycle arrest biomarkers are indicators of both sides of this complex physiology. PMID:26044835

  2. Serum metabolomic profiles from patients with acute kidney injury: a pilot study.

    PubMed

    Sun, Jinchun; Shannon, Melissa; Ando, Yosuke; Schnackenberg, Laura K; Khan, Nasim A; Portilla, Didier; Beger, Richard D

    2012-04-15

    Low sensitivity of current clinical markers (serum creatinine and blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AKI. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients.

  3. Serum Metabolomic Profiles from Patients with Acute Kidney Injury: A Pilot Study

    PubMed Central

    Sun, Jinchun; Shannon, Melissa; Ando, Yosuke; Schnackenberg, Laura K.; Khan, Nasim A.; Portilla, Didier; Beger, Richard D

    2012-01-01

    Low sensitivity of current clinical markers (serum creatinine, blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AKI. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients. PMID:22429878

  4. Development of Inpatient Risk Stratification Models of Acute Kidney Injury for Use in Electronic Health Records

    PubMed Central

    Matheny, Michael E.; Miller, Randolph A.; Ikizler, T. Alp; Waitman, Lemuel R.; Denny, Joshua C.; Schildcrout, Jonathan S.; Dittus, Robert S.; Peterson, Josh F.

    2016-01-01

    Objective Patients with hospital-acquired acute kidney injury (AKI) are at risk for increased mortality and further medical complications. Evaluating these patients with a prediction tool easily implemented within an electronic health record (EHR) would identify high risk patients prior to the development of AKI, and could prevent iatrogenically induced episodes of AKI and improve clinical management. Methods We used structured clinical data acquired from an EHR to identify patients with normal kidney function for admissions from August 1st, 1999 to July 31st, 2003. Using administrative, computerized provider order entry, and laboratory test data, we developed a 3-level risk stratification model to predict each of two severity levels of in-hospital AKI as defined by RIFLE criteria. The severity levels were defined as 150% or 200% of baseline serum creatinine. Model discrimination and calibration was evaluated using 10-fold cross-validation. Results Cross-validation of the models resulted in area under the receiver operating characteristic (AUC) curves of 0.75 (150% elevation) and 0.78 (200% elevation). Both models were adequately calibrated as measured by the Hosmer-Lemeshow goodness-of-fit test chi-squared values of 9.7 (p = 0.29) and 12.7 (p = 0.12), respectively. Conclusions We generated risk prediction models for hospital-acquired AKI using only commonly available electronic data. The models identify patients at high risk for AKI who might benefit from early intervention or increased monitoring. PMID:20354229

  5. Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury.

    PubMed

    Kapitsinou, Pinelopi P; Jaffe, Jonathan; Michael, Mark; Swan, Christina E; Duffy, Kevin J; Erickson-Miller, Connie L; Haase, Volker H

    2012-05-01

    Acute kidney injury (AKI) due to ischemia is an important contributor to the progression of chronic kidney disease (CKD). Key mediators of cellular adaptation to hypoxia are oxygen-sensitive hypoxia-inducible factors (HIF), which are regulated by prolyl-4-hydroxylase domain (PHD)-containing dioxygenases. While activation of HIF protects from ischemic cell death, HIF has been shown to promote fibrosis in experimental models of CKD. The impact of HIF activation on AKI-induced fibrosis has not been defined. Here, we investigated the role of pharmacologic HIF activation in AKI-associated fibrosis and inflammation. We found that pharmacologic inhibition of HIF prolyl hydroxylation before AKI ameliorated fibrosis and prevented anemia, while inhibition of HIF prolyl hydroxylation in the early recovery phase of AKI did not affect short- or long-term clinical outcome. Therefore, preischemic targeting of the PHD/HIF pathway represents an effective therapeutic strategy for the prevention of CKD resulting from AKI, and it warrants further investigation in clinical trials. PMID:22262480

  6. Strategies for prevention of acute kidney injury in cardiac surgery: an integrative review

    PubMed Central

    Santana-Santos, Eduesley; Marcusso, Marila Eduara Fátima; Rodrigues, Amanda Oliveira; de Queiroz, Fernanda Gomes; de Oliveira, Larissa Bertacchini; Rodrigues, Adriano Rogério Baldacin; Palomo, Jurema da Silva Herbas

    2014-01-01

    Acute kidney injury is a common complication after cardiac surgery and is associated with increased morbidity and mortality and increased length of stay in the intensive care unit. Considering the high prevalence of acute kidney injury and its association with worsened prognosis, the development of strategies for renal protection in hospitals is essential to reduce the associated high morbidity and mortality, especially for patients at high risk of developing acute kidney injury, such as patients who undergo cardiac surgery. This integrative review sought to assess the evidence available in the literature regarding the most effective interventions for the prevention of acute kidney injury in patients undergoing cardiac surgery. To select the articles, we used the CINAHL and MedLine databases. The sample of this review consisted of 16 articles. After analyzing the articles included in the review, the results of the studies showed that only hydration with saline has noteworthy results in the prevention of acute kidney injury. The other strategies are controversial and require further research to prove their effectiveness. PMID:25028954

  7. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

    PubMed

    de Bragança, Ana C; Volpini, Rildo A; Mehrotra, Purvi; Andrade, Lúcia; Basile, David P

    2016-07-01

    Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

  8. Predictors and in-hospital outcomes of preoperative acute kidney injury in patients with type A acute aortic dissection

    PubMed Central

    Wang, Xiao; Ren, Hong-Mei; Hu, Chun-Yan; Que, Bin; Ai, Hui; Wang, Chun-Mei; Sun, Li-Zhong; Nie, Shao-Ping

    2016-01-01

    Background Acute kidney injury (AKI) is common after surgery for acute aortic dissection (AAD) and increases in-hospital and long-term mortality. However, few data exist on the clinical and prognostic relevance of early preoperative AKI in patients with type A AAD. We aimed to determine the incidence and predictors of preoperative AKI and the impact of AKI on in-hospital outcomes in patients with type A AAD. Methods From May 2009 to June 2014, we retrospectively enrolled 178 patients admitted to our hospital within 48 h from symptom onset and receiving open surgery for type A AAD. The patients were divided into no AKI and AKI groups and staged with AKI severity according to the KDIGO criteria before surgery. Results AKI occurred in 41 patients (23.0%). The incidence of in-hospital complications was significantly higher in patients with preoperative AKI compared to no AKI (41.5% vs. 9.5%, P < 0.001), including renal infarction (7.3% vs. 0, P = 0.012), and it increased with AKI severity (Ptrend < 0.001). Patients with AKI had higher in-hospital mortality compared with patients without AKI, although no significant difference was found (14.6% vs. 5.1%, P = 0.079). Multivariate analysis indicated that male gender, diastolic blood pressure on admission and bilateral renal artery involvement were independent predictors of preoperative AKI in patients with type A AAD. Conclusions Early AKI before surgery was common in patients with type A AAD, and was associated with increased in-hospital complications. Male gender, diastolic blood pressure on admission and bilateral renal artery involvement were major predictors for preoperative AKI. PMID:27781058

  9. Utility of citrate dialysate in management of acute kidney injury in children.

    PubMed

    Hanevold, Coral; Lu, Sharon; Yonekawa, Karyn

    2010-10-01

    Dialysis concentrate acidified with citrate as opposed to acetate has been reported to prevent clotting in hemodialysis circuits, and improve dialysis efficiency in adults. There is no information on its use in children. The purpose of the study was to evaluate the utility of citrate dialysate for renal replacement therapy in a pediatric population with acute kidney injury. We performed a retrospective review of our experience using Citrasate(®) concentrate from December 2007 to August 2009. All treatments were provided using the Fresenius 2008 dialysis machine. Citrasate(®) was utilized in 7 children aged 60.3±51.0 months (mean±SD), range 13 months to 12 years. The number of treatments varied from 4 to 31 (mean 12±8 treatments) for a total of 89 treatments. Rare sporadic mild hypocalcemia was noted but could not be definitively linked with the use of Citrasate(®). Four children also required low-dose heparin (3.6-15 U/kg/h) due to clotting. Activated clotting times (when checked) were not affected by this low-dose heparin therapy. Some degree of clotting occurred in 21 of 89 (23.5%) treatments. Early termination of treatment due to thrombosis was required in 7 of 89 (7.8%) treatments. In summary, use of Citrasate(®) dialysis concentrate was well tolerated in critically ill children with acute kidney injury. Citrasate(®) reduced but did not completely eliminate the need for heparin in our population. Further study in a more diverse population would be helpful. PMID:21040414

  10. Anuric Acute Kidney Injury Induced by Acute Mountain Sickness Prophylaxis With Acetazolamide

    PubMed Central

    Castle Alvarez-Maza, James; Novak, James E.

    2014-01-01

    Acetazolamide (ACZ) is a sulfonamide derivative that inhibits carbonic anhydrase and is the mainstay for prevention and treatment of acute mountain sickness (AMS). Acute kidney injury (AKI) is not well recognized as a complication of ACZ ingestion, especially when low doses are used for short periods of time. We report a case of a healthy, middle-aged man who developed severe AKI after the ingestion of ACZ for AMS prophylaxis. The patient presented with bilateral flank pain and anuric AKI without radiographic signs of obstructive uropathy. All blood and urine testing to determine the cause of AKI were negative or normal. The patient required 2 sessions of hemodialysis due to worsening metabolic derangements, which included severe anion gap metabolic acidosis and hyperphosphatemia. Renal function returned to baseline after 96 hours of supportive care. The pathogenesis of AKI in our patient was attributed to ACZ-induced sulfonamide crystalluria causing intratubular obstruction and retrograde urine flow, but not intraureteric precipitation or obstructive uropathy. This classic presentation of anuric AKI and renal colic has been previously described with higher doses of ACZ for prolonged periods of time but never with low doses for AMS prophylaxis such as in our patient (total dose of 1250 mg within 48 hours). Our case highlights the risk of adverse renal outcomes following ACZ ingestion, even in previously healthy individuals, and suggests that increased fluid intake may be advisable for travelers taking ACZ prophylaxis. PMID:25264540

  11. Clinical therapeutic strategies for early stage of diabetic kidney disease

    PubMed Central

    Kitada, Munehiro; Kanasaki, Keizo; Koya, Daisuke

    2014-01-01

    Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuous screening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression. PMID:24936255

  12. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

    PubMed Central

    Heincelman, Marc; Karakala, Nithin; Rockey, Don C.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes) felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL. PMID:27722178

  13. Acute Peritoneal Dialysis in Neonates with Acute Kidney Injury and Hypernatremic Dehydration

    PubMed Central

    Yildiz, Nurdan; Erguven, Müferet; Yildiz, Metin; Ozdogan, Tutku; Turhan, Pinar

    2013-01-01

    ♦ Objective: We aimed to evaluate the efficacy of acute peritoneal dialysis (PD) and clinical outcomes in neonates with acute kidney injury (AKI) and hypernatremic dehydration. ♦ Methods: The medical records of 15 neonates with AKI and hypernatremic dehydration who were treated with acute PD were reviewed. The diagnoses were AKI with hypernatremic dehydration with or without sepsis in 13 patients and AKI with hypernatremia and congenital nephropathy in 2 patients. The main indications for PD were AKI with some combination of oligoanuria, azotemia, hyperuricemia, and metabolic acidosis unresponsive to initial intensive medical treatment. ♦ Results: The mean age of the patients at dialysis initiation was 11.9 ± 9 days, and the mean duration of PD was 6.36 ± 4.8 days. In 7 patients (46.7%), hypotension required the use of vasopressors, and in 6 patients (40%), mechanical ventilation was required. Peritoneal dialysis-related complications occurred in 7 patients (46.7%), the most common being catheter malfunction (n = 6). Four episodes of peritonitis occurred in the 15 patients (26.7%), 2 episodes in patients with congenital renal disease and 2 episodes in patients with sepsis and multiorgan failure, who did not survive. Congenital renal disease, septicemia, and the need for mechanical ventilation were important factors influencing patient survival. All patients with no pre-existing renal disease or sepsis recovered their renal function and survived. ♦ Conclusions: In neonates with AKI and hypernatremic dehydration, PD is safe and successful, and in patients without congenital renal disease or sepsis, the prognosis is good. Peritoneal dialysis should be the treatment of choice in neonates with AKI and hypernatremic dehydration who do not respond to appropriate med ical treatment. PMID:23123669

  14. Acute effects of aldosterone on the epithelial Na channel in rat kidney

    PubMed Central

    Frindt, Gustavo

    2014-01-01

    The acute effects of aldosterone administration on epithelial Na channels (ENaC) in rat kidney were examined using electrophysiology and immunodetection. Animals received a single injection of aldosterone (20 μg/kg body wt), which reduced Na excretion over the next 3 h. Channel activity was assessed in principal cells of cortical collecting ducts as amiloride-sensitive whole cell clamp current (INa). INa averaged 100 pA/cell, 20–30% of that reported for the same preparation under conditions of chronic stimulation. INa was negligible in control animals that did not receive hormone. The acute physiological response correlated with changes in ENaC processing and trafficking. These effects included increases in the cleaved forms of α-ENaC and γ-ENaC, assessed by Western blot, and increases in the surface expression of β-ENaC and γ-ENaC measured after surface protein biotinylation. These changes were qualitatively and quantitatively similar to those of chronic stimulation. This suggests that altered trafficking to or from the apical membrane is an early response to the hormone and that later increases in channel activity require stimulation of channels residing at the surface. PMID:25520012

  15. Why do young people with chronic kidney disease die early?

    PubMed Central

    Kumar, Shankar; Bogle, Richard; Banerjee, Debasish

    2014-01-01

    Cardiovascular disease poses the greatest risk of premature death seen among patients with chronic kidney disease (CKD). Up to 50% of mortality risk in the dialysis population is attributable to cardiovascular disease and the largest relative excess mortality is observed in younger patients. In early CKD, occlusive thrombotic coronary disease is common, but those who survive to reach end-stage renal failure requiring dialysis are more prone to sudden death attributable mostly to sudden arrhythmic events and heart failure related to left ventricular hypertrophy, coronary vascular calcification and electrolyte disturbances. In this review, we discuss the basis of the interaction of traditional risk factors for cardiovascular disease with various pathological processes such as endothelial dysfunction, oxidative stress, low grade chronic inflammation, neurohormonal changes and vascular calcification and stiffness which account for the structural and functional cardiac changes that predispose to excess morbidity and mortality in young people with CKD. PMID:25374808

  16. Early chronic kidney disease: diagnosis, management and models of care.

    PubMed

    Wouters, Olivier J; O'Donoghue, Donal J; Ritchie, James; Kanavos, Panos G; Narva, Andrew S

    2015-08-01

    Chronic kidney disease (CKD) is prevalent in many countries, and the costs associated with the care of patients with end-stage renal disease (ESRD) are estimated to exceed US$1 trillion globally. The clinical and economic rationale for the design of timely and appropriate health system responses to limit the progression of CKD to ESRD is clear. Clinical care might improve if early-stage CKD with risk of progression to ESRD is differentiated from early-stage CKD that is unlikely to advance. The diagnostic tests that are currently used for CKD exhibit key limitations; therefore, additional research is required to increase awareness of the risk factors for CKD progression. Systems modelling can be used to evaluate the impact of different care models on CKD outcomes and costs. The US Indian Health Service has demonstrated that an integrated, system-wide approach can produce notable benefits on cardiovascular and renal health outcomes. Economic and clinical improvements might, therefore, be possible if CKD is reconceptualized as a part of primary care. This Review discusses which early CKD interventions are appropriate, the optimum time to provide clinical care, and the most suitable model of care to adopt.

  17. Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy

    PubMed Central

    Ahn, Pyoung; Min, Hyun-Jun; Park, Sang-Hyun; Lee, Byoung-Mu; Choi, Myung-Jin; Yoon, Jong-Woo

    2013-01-01

    Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that statin-induced muscle injury was aggravated by hypothyroidism resulting in her full-blown rhabdomyolysis. Although this patient was successfully treated with continuous venovenous hemofiltration and L-thyroxin replacement, rhabdomyolysis with acute kidney injury is a potentially life-threatening disorder. Physicians must pay special attention to the possible presence of subclinical hypothyroidism when administering statins in patients with hypercholesterolemia. PMID:24396699

  18. Role of early systemic inflammatory response in simultaneous pancreas-kidney transplantation.

    PubMed

    Piros, L; Fazakas, J; Smudla, A; Földes, K; Langer, R M

    2012-09-01

    Pancreas grafts are susceptible to surgical complications mostly related to exocrine secretions and the low microcirculatory blood flow through the gland. During simultaneous kidney-pancreas transplantation, the systemic response depends on reperfusion of two organs acute graft pancreatitis, immunotherapy, coagulopathy, bleeding, and other factors. We performed a retrospective review of 10 adult simultaneous pancreas-kidney transplant patients to evaluate progression of early postoperative inflammation in the absence of infection. All patients were treated with four-drug therapy. We performed analyses of procalcitonin (PCT), C-reactive protein, serum creatinine, amylase, and lipase levels over the first 5 postoperative days. Relatively high peak PCT levels (maximum 130 ng/mL) were reached within 24 to 48 hours postoperatively followed by a moderate decrease. Consistent with this observation, the serum creatinine, amylase, and lipase levels decreased continuously to normal concentrations within the first week. The increased PCT levels seemed depend upon the surgical procedure and intraoperative events. PCT was superior to C-reactive protein to discriminate infection from inflammation in this setting. The dynamics of PCT levels, rather than absolute values, seemed to be important. Lack of a decrease in PCT levels after the peak, suggested an infectious complication or the development of sepsis. Monitoring and assessment of PCT levels may help in early recognition of infection and institution of therapy.

  19. The growth of acute kidney injury: a rising tide or just closer attention to detail?

    PubMed Central

    Siew, Edward D; Davenport, Andrew

    2015-01-01

    Acute kidney injury (AKI), previously termed acute renal failure, is associated with increased mortality, prolonged hospital stay, and accelerated chronic kidney disease (CKD). Over the past 2 decades, dramatic rises in the incidences of AKI have been reported, particularly within the United States. The question arises as to whether these changes reflect actual increases in disease incidence, or are potentially explained by the introduction of consensus definitions that rely on small standardized changes in serum creatinine, changes in coding and reimbursement, or increasingly available and more liberal use of dialysis. In this review, we explore the secular trends in AKI incidence in North America and Western Europe and its potential contributors. PMID:25229340

  20. Percutaneous radiofrequency ablation-induced perinephric hematoma with acute renal failure in a solitary kidney.

    PubMed

    Zhao, Lee C; Chan, Sarah W; Macejko, Amanda M; Lin, William W

    2008-07-01

    Iatrogenic occurrences (including radiologically guided renal biopsy, shockwave lithotripsy, and minimally invasive ablative procedures) of subcapsular hematoma that lead to acute renal failure are rare but serious. The advancement of minimally invasive procedures has led to an increase in this complication, especially in patients with a solitary kidney. Fortunately, prompt surgical evacuation of the hematoma in these patients allows decompression of the renal parenchyma and recovery of renal function. We report a case of acute renal failure in a patient with a solitary kidney that resulted from a subcapsular hematoma as a complication of radiofrequency ablation.

  1. Septic versus non-septic acute kidney injury in critically ill patients: characteristics and clinical outcomes

    PubMed Central

    Cruz, Marília Galvão; Dantas, João Gabriel Athayde de Oliveira; Levi, Talita Machado; Rocha, Mário de Seixas; de Souza, Sérgio Pinto; Boa-Sorte, Ney; de Moura, Carlos Geraldo Guerreiro; Cruz, Constança Margarida Sampaio

    2014-01-01

    Objective This study aimed to describe and compare the characteristics and clinical outcomes of patients with septic and non-septic acute kidney injury. Methods This study evaluated an open cohort of 117 critically ill patients with acute kidney injury who were consecutively admitted to an intensive care unit, excluding patients with a history of advanced-stage chronic kidney disease, kidney transplantation, hospitalization or death in a period shorter than 24 hours. The presence of sepsis and in-hospital death were the exposure and primary variables in this study, respectively. A confounding analysis was performed using logistic regression. Results No significant differences were found between the mean ages of the groups with septic and non-septic acute kidney injury [65.30±21.27 years versus 66.35±12.82 years, respectively; p=0.75]. In the septic and non-septic acute kidney injury groups, a predominance of females (57.4% versus 52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%, respectively; p=0.49) was observed. Compared with the non-septic patients, the patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II score [21.73±7.26 versus 15.75±5.98; p<0.001)] and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure (p<0.001) were more common in the non-septic patients. Septic acute kidney injury was associated with a greater number of patients who required dialysis (p=0.001) and a greater number of deaths (p<0.001); however, renal function recovery was more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI: 3.73-25.58) were associated with death in the multivariate analysis. Conclusion Sepsis was an independent predictor of death. Significant differences were found between the characteristics and clinical outcomes of patients with septic versus non-septic acute kidney

  2. Cell therapy, advanced materials, and new approaches to acute kidney injury.

    PubMed

    Yevzlin, Alexander S; Humes, H David

    2009-12-01

    Acute renal failure (ARF) is a common clinical syndrome characterized by an abrupt deterioration in kidney function, resulting in abnormalities in volume-regulatory, metabolic-regulatory, excretory, and endocrine functions. Despite decades of improvements in the provision of intensive care, and specifically in the provision of renal replacement therapy, the morbidity and mortality associated with acute kidney injury (AKI) remain extremely high. This article highlights novel cell therapies, advanced materials, and approaches to AKI with the aim of illuminating a potential path for future basic, translational, and clinical research using these novel modalities.

  3. Multidisciplinary strategies in the management of early chronic kidney disease.

    PubMed

    Martínez-Ramírez, Héctor R; Cortés-Sanabria, Laura; Rojas-Campos, Enrique; Hernández-Herrera, Aurora; Cueto-Manzano, Alfonso M

    2013-11-01

    Chronic kidney disease (CKD) is a worldwide epidemic especially in developing countries, with clear deficiencies in identification and treatment. Better care of CKD requires more than only economic resources, utilization of health research in policy-making and health systems changes that produce better outcomes. A multidisciplinary approach may facilitate and improve management of patients from early CKD in the primary health-care setting. This approach is a strategy for improving comprehensive care, initiating and maintaining healthy behaviors, promoting teamwork, eliminating barriers to achieve goals and improving the processes of care. A multidisciplinary intervention may include educational processes guided by health professional, use of self-help groups and the development of a CKD management plan. The complex and fragmented care management of patients with CKD, associated with poor outcome, enhances the importance of implementing a multidisciplinary approach in the management of this disease from the early stages. Multidisciplinary strategies should focus on the needs of patients (to increase their empowerment) and should be adapted to the resources and health systems prevailing in each country; its systematic implementation can help to improve patient care and slow the progression of CKD. PMID:24215785

  4. Preserved Renal Function in Kidney Transplantation over a Thrombosed Aortobifemoral Bypass Graft: The Role of Retrograde Flow and Early Thrombolysis.

    PubMed

    Pampa-Saico, Saúl; Jiménez-Alvaro, Sara; Caravaca-Fontán, Fernando; Fernández-Rodríguez, Ana; Rivera-Gorrín, Maite; Sánchez, Juan; Chinchilla, Antonio; Marcén, Roberto

    2016-01-01

    Aortobifemoral bypass (ABFB) thrombosis is not uncommon, and when the artery of a renal graft is implanted on a bypass the risk of graft loss is high. We report the case of a 48-year-old woman with a previous history of ABFB under antiplatelet therapy and a kidney allograft implanted on the vascular prosthesis, who presented with acute limb ischemia and severe renal impairment. Imaging techniques revealed a complete thrombosis of the proximal left arm of the ABFB. However, a faint retrograde flow over the graft was observed thanks to the recanalization of distal left bypass by collateral native arteries. This unusual situation not previously reported in a kidney transplant setting, together with an early diagnosis, allowed graft survival until an early local thrombolysis resolved the problem. Two years later, renal function remains normal. PMID:27579209

  5. Preserved Renal Function in Kidney Transplantation over a Thrombosed Aortobifemoral Bypass Graft: The Role of Retrograde Flow and Early Thrombolysis

    PubMed Central

    Jiménez-Alvaro, Sara; Fernández-Rodríguez, Ana; Rivera-Gorrín, Maite; Sánchez, Juan; Chinchilla, Antonio; Marcén, Roberto

    2016-01-01

    Aortobifemoral bypass (ABFB) thrombosis is not uncommon, and when the artery of a renal graft is implanted on a bypass the risk of graft loss is high. We report the case of a 48-year-old woman with a previous history of ABFB under antiplatelet therapy and a kidney allograft implanted on the vascular prosthesis, who presented with acute limb ischemia and severe renal impairment. Imaging techniques revealed a complete thrombosis of the proximal left arm of the ABFB. However, a faint retrograde flow over the graft was observed thanks to the recanalization of distal left bypass by collateral native arteries. This unusual situation not previously reported in a kidney transplant setting, together with an early diagnosis, allowed graft survival until an early local thrombolysis resolved the problem. Two years later, renal function remains normal. PMID:27579209

  6. Acute kidney injury: intravenous fluid to prevent contrast-induced AKI.

    PubMed

    Weisbord, Steven D; Palevsky, Paul M

    2009-05-01

    Trials that compared sodium bicarbonate and sodium chloride for the prevention of contrast-induced acute kidney injury have yielded highly conflicting results. The authors of a recent meta-analysis endeavored to provide a definitive assessment of the relative efficacy of these two intravenous fluids.

  7. [McArdle disease presenting with rhabdomyolisis and acute kidney injury].

    PubMed

    Costa, Rui; Castro, Rui; Costa, Alexandre; Taipa, Ricardo; Vizcaíno, Ramon; Morgado, Teresa

    2013-01-01

    McArdle disease typically presents in childhood or young adults with myalgia, exercise intolerance, cramps and myoglobinuria. Deficiency of myophosphorylase enzyme results in inability to degrade glycogen stores, causing glycogen accumulation in muscle tissue and energy deficit. Evolution with rhabdomiolysis may occur and can be complicated with acute kidney injury but rarely, in about 11% of cases, is the initial disease manifestation. We report a case of McArdle Disease in a 38-year-old male patient. The disease went unrecognized despite previous symptoms (myalgia, exercise intolerance and single myoglobinuria episode) until an episode of rhabdomyolisis complicated with oliguric acute kidney injury requiring hemodialysis. The kidney biopsy showed evidence of acute tubular necrosis. Despite normalization of renal function, muscle lysis markers remained abnormal. Metabolic myopathy was suspected and a muscle biopsy was performed. It showed subsarcolemic glycogen deposition and absence of myophosphorylase activity. This case-report underlines the importance of considering metabolic myopathy in patients with acute kidney injury and severe rhabdomyolisis.

  8. VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury

    PubMed Central

    Leonard, Ellen C.; Friedrich, Jessica L.; Basile, David P.

    2008-01-01

    Acute kidney injury induced by renal ischemia-reperfusion (I/R) compromises microvascular density and predisposes to chronic kidney disease (CKD) and sodium-dependent hypertension. VEGF-121 was administered to rats fed a standard (0.4%) sodium diet at various times following recovery from I/R injury for up to 35 days. VEGF-121 had no effect on the initial loss of renal function, as indicated by serum creatinine levels measured 24 h after injury. Serum creatinine levels declined thereafter, indicative of renal repair. Rats were then switched to an elevated (4.0%) sodium diet for an additional 28 days to induce CKD. The 4.0% sodium diet enhanced renal hypertrophy, interstitial volume, albuminuria, and cardiac hypertrophy relative to postischemic animals maintained on the 0.4% sodium diet. Administration of VEGF-121 from day 0 to 14, day 0 to 35, or day 3 to 35 after I/R suppressed the effects of sodium diet on CKD development, while delayed administration of VEGF-121 from day 21 to 35 had no effect. Endothelial nitric oxide synthase protein levels were upregulated in postischemic animals, and this effect was significantly increased by the 4.0% sodium diet but was not influenced by prior treatment with VEGF. Conversely, microvascular density was preserved in postischemic animals treated with VEGF-121 relative to vehicle-treated postischemic animals. These data suggest that early, but not delayed, treatment with VEGF-121 can preserve vascular structure after ischemia and influence chronic renal function in response to elevated sodium intake. PMID:18799550

  9. The Related Risk Factors Analysis of Snake-Bite Induced Acute Kidney Injury

    PubMed Central

    Li, Wei; Chen, Fang; Wu, Shukun

    2016-01-01

    Background The pathogenic mechanism of snake-bite induced acute kidney injury (AKI) remains unclear. Analyzing the risk factors for snake-bite induced AKI may provide the guidance needed for AKI prevention and early treatment. Material/Methods This retrospective study included 119 snake-bite patients who were hospitalized at the emergency department of Sichuan Provincial People’s Hospital from January 2011 to September 2013. The patients were divided into AKI and non-AKI groups according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Gender, age, and clinical examination data of the patients were recorded. The Mann-Whitney U test and Fisher exact test were performed to analyze the collected data; preliminary analysis of independent risk factors was performed with multivariate logistic regression. Results Among the snake-bite patients, 98.3% were farmers. The mean age of patients was 46±12 years. Of the 119 patients (13.4%), 16 suffered from AKI. There were statistically significant differences between the AKI and non-AKI groups with respect to age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin. Preliminary analysis with multivariate logistic regression showed that advanced age and increased time interval from snake bite to antivenin therapy might be independent risk factors for snake-bite induced AKI. Conclusions Age, time interval from snake bite to antivenin therapy, creatine kinase, blood myoglobin, advanced age, regional lymphadenopathy, incision drainage, and hemoglobin were risk factors for snake-bite induced AKI. Advanced age and delayed antivenin therapy might be independent risk factors for snake-bite induced AKI. PMID:27377078

  10. Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice

    PubMed Central

    Skrypnyk, Nataliya I.; Harris, Raymond C.; de Caestecker, Mark P.

    2013-01-01

    Ischemia-reperfusion induced acute kidney injury (IR-AKI) is widely used as a model of AKI in mice, but results are often quite variable with high, often unreported mortality rates that may confound analyses. Bilateral renal pedicle clamping is commonly used to induce IR-AKI, but differences between effective clamp pressures and/or renal responses to ischemia between kidneys often lead to more variable results. In addition, shorter clamp times are known to induce more variable tubular injury, and while mice undergoing bilateral injury with longer clamp times develop more consistent tubular injury, they often die within the first 3 days after injury due to severe renal insufficiency. To improve post-injury survival and obtain more consistent and predictable results, we have developed two models of unilateral ischemia-reperfusion injury followed by contralateral nephrectomy. Both surgeries are performed using a dorsal approach, reducing surgical stress resulting from ventral laparotomy, commonly used for mouse IR-AKI surgeries. For induction of moderate injury BALB/c mice undergo unilateral clamping of the renal pedicle for 26 min and also undergo simultaneous contralateral nephrectomy. Using this approach, 50-60% of mice develop moderate AKI 24 hr after injury but 90-100% of mice survive. To induce more severe AKI, BALB/c mice undergo renal pedicle clamping for 30 min followed by contralateral nephrectomy 8 days after injury. This allows functional assessment of renal recovery after injury with 90-100% survival. Early post-injury tubular damage as well as post injury fibrosis are highly consistent using this model. PMID:23963468

  11. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsis-induced renal microcirculatory failure and acute kidney injury.

    PubMed

    Wang, Zhen; Holthoff, Joseph H; Seely, Kathryn A; Pathak, Elina; Spencer, Horace J; Gokden, Neriman; Mayeux, Philip R

    2012-02-01

    Acute kidney injury is a frequent and serious complication of sepsis. To better understand the development of sepsis-induced acute kidney injury, we performed the first time-dependent studies to document changes in renal hemodynamics and oxidant generation in the peritubular microenvironment using the murine cecal ligation and puncture (CLP) model of sepsis. CLP caused an increase in renal capillary permeability at 2 hours, followed by decreases in mean arterial pressure, renal blood flow (RBF), and renal capillary perfusion at 4 hours, which were sustained through 18 hours. The decline in hemodynamic parameters was associated with hypoxia and oxidant generation in the peritubular microenvironment and a decrease in glomerular filtration rate. The role of oxidants was assessed using the superoxide dismutase mimetic/peroxynitrite scavenger MnTMPyP [Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin]. At 10 mg/kg administered 6 hours after CLP, MnTMPyP did not alter blood pressure, but blocked superoxide and peroxynitrite generation, reversed the decline in RBF, capillary perfusion, and glomerular filtration rate, preserved tubular architecture, and increased 48-hour survival. However, MnTMPyP administered at CLP did not prevent capillary permeability or the decrease in RBF and capillary perfusion, which suggests that these early events are not mediated by oxidants. These data demonstrate that renal hemodynamic changes occur early after sepsis and that targeting the later oxidant generation can break the cycle of injury and enable the microcirculation and renal function to recover.

  12. Design of Clinical Trials in Acute Kidney Injury: Lessons from the Past and Future Directions.

    PubMed

    Weisbord, Steven D; Palevsky, Paul M

    2016-01-01

    Acute kidney injury (AKI) is a common condition with multiple etiologies and variable clinical findings and pathologic manifestations. AKI is associated with serious adverse clinical outcomes, including the development of de novo chronic kidney disease, accelerated progression of pre-existing chronic kidney disease, end-stage kidney disease, and increased mortality. Past research has advanced our understanding of the pathophysiology, epidemiology, and outcomes of AKI significantly, however, little progress has been made in the development of evidence-based interventions for its prevention and treatment. In this review, we discuss key considerations in the design of clinical trials in AKI and highlight significant methodologic limitations that precluded many past studies from determining the effectiveness of preventive and therapeutic strategies for this common and serious condition.

  13. Effect of acute occlusion of left renal vein on the kidney: an experimental study in dogs.

    PubMed

    Khan, S A; Ashraf, S M; Naim, M; Azfar, M

    1994-04-01

    To study the effects of acute ligation of the left renal vein an experimental study was carried out on 16 Mongrel dogs out of 18 of which 2 had died postoperatively. The right kidney served as control. Changes immediately after ligation were recorded; subsequently the dogs were sacrificed in 4 groups comprising 4 in each at intervals of 24 hours, one week, 4 weeks and 6 weeks. Both the kidneys were removed and gross and microscopic changes were noted. In all cases atrophy of the ligated kidney due to tubular atrophy and fibrosis were seen in spite of good collaterals. It is concluded that left renal vein ligation in dogs is not safe for the kidney, though it is not fatal.

  14. MicroRNA-21 (miR-21) expression in hypothermic machine perfusate may be predictive of early outcomes in kidney transplantation.

    PubMed

    Khalid, Usman; Ablorsu, Elijah; Szabo, Laszlo; Jenkins, Robert H; Bowen, Timothy; Chavez, Rafael; Fraser, Donald J

    2016-02-01

    Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA-21 (miR-21) expression in the kidney following acute kidney injury. This study investigated the potential of miR-21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR-21 was found to be readily detectable in HMP by RT-qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117-1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post-perfusion. MiR-21 quantification at 60 min post-perfusion correlated with eGFR at 6 and 12 months post-transplantation. These data suggest that miR-21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR-21 may be such a marker.

  15. Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis.

    PubMed

    Kuma, Akihiro; Yamada, Sohsuke; Wang, Ke-Yong; Kitamura, Noriaki; Yamaguchi, Takahiro; Iwai, Yoshiko; Izumi, Hiroto; Tamura, Masahito; Otsuji, Yutaka; Kohno, Kimitoshi

    2014-01-01

    WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN). We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR) and WNT10A expression using kidney biopsies from 20 patients with AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR than WNT10A-negative patients. However, changes in kidney function were not related to the level of expression of other WNT family members. Furthermore, there was positive correlation between WNT10A and α-SMA expression. We next investigated the involvement of WNT10A in kidney fibrosis processes using COS1 cells, a kidney fibroblast cell line. WNT10A overexpression increased the level of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A overexpression renders cells resistant to apoptosis induced by hydrogen peroxide and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate with kidney dysfunction in AIN. PMID:25054240

  16. Kidney Dysplasia

    MedlinePlus

    ... following early in life: blood-filtering treatments called dialysis a kidney transplant Children with dysplasia in only ... mild dysplasia of both kidneys may not need dialysis or a kidney transplant for several years. Kidney ...

  17. Acute Kidney Injury in Elderly Patients With Chronic Kidney Disease: Do Angiotensin-Converting Enzyme Inhibitors Carry a Risk?

    PubMed

    Chaumont, Martin; Pourcelet, Aline; van Nuffelen, Marc; Racapé, Judith; Leeman, Marc; Hougardy, Jean-Michel

    2016-06-01

    In contrast to angiotensin receptor blockers (ARBs), mainly excreted by the liver, the dosage of angiotensin-converting enzyme (ACE) inhibitors, cleared by the kidney, must be adapted to account for renal clearance in patients with chronic kidney disease (CKD) to avoid acute kidney injury (AKI). Community-acquired AKI and the use of ACE inhibitors or ARBs in the emergency department were retrospectively assessed in 324 patients with baseline stage 3 or higher CKD. After stepwise regression analysis, the use of ACE inhibitors (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.1; P=.02) and the presence of dehydration (OR, 30.8; 95% CI, 3.9-239.1) were associated with AKI. A total of 45% of patients using ACE inhibitors experienced overdosing, which causes most of the excess risk of AKI. These results suggest that dosage adjustment of ACE inhibitors to renal function or substitution of ACE inhibitors with ARBs could reduce the incidence of AKI. Moreover, ACE inhibitors and ARBs should be stopped in cases of dehydration. PMID:27080620

  18. Acute kidney injury in a shepherd with severe malaria: a case report

    PubMed Central

    Boushab, Boushab Mohamed; Fall-Malick, Fatim-Zahra; Savadogo, Mamoudou; Basco, Leonardo Kishi

    2016-01-01

    Malaria is one of the main reasons for outpatient consultation and hospitalization in Mauritania. Although four Plasmodium species, ie, Plasmodium (P.) falciparum, P. vivax, P. malariae, and P. ovale, cause malaria in Mauritania, recent data on their frequency is lacking. Since infections with P. falciparum generally result in serious disease, their identification is important. We report a case of oliguric renal injury associated with malaria in a 65-year-old shepherd. Clinical manifestations included anemia, oliguria, and elevated creatinine and urea. The rapid diagnostic test for malaria and microscopic examination of blood smears were positive for P. falciparum. On the basis of this, the patient was diagnosed as having acute kidney injury as a complication of severe malaria. The patient was treated for malaria with intravenous quinine for 4 days, followed by 3 days of oral treatment. Volume expansion, antipyretic treatment, and diuretics were administered. He also had two rounds of dialysis after which he partially recovered renal function. This outcome is not always the rule. Prognosis depends much on early diagnosis and appropriate supportive treatment. PMID:27785088

  19. Acute kidney injury following liver transplantation: a systematic review of published predictive models.

    PubMed

    Caragata, R; Wyssusek, K H; Kruger, P

    2016-03-01

    Acute kidney injury is a frequent postoperative complication amongst liver transplant recipients and is associated with increased morbidity and mortality. This systematic review analysed the existing predictive models, in order to solidify current understanding. Articles were selected for inclusion if they described the primary development of a clinical prediction model (either an algorithm or risk score) to predict AKI post liver transplantation. The database search yielded a total of seven studies describing the primary development of a prediction model or risk score for the development of AKI following liver transplantation. The models span thirteen years of clinical research and highlight a gradual change in the definitions of AKI, emphasising the need to employ standardised definitions for subsequent studies. Collectively, the models identify a diverse range of predictive factors with several common trends. They emphasise the impact of preoperative renal dysfunction, liver disease severity and aetiology, metabolic risk factors as well as intraoperative variables including measures of haemodynamic instability and graft quality. Although several of the models address postoperative parameters, their utility in predictive modelling seems to be of questionable relevance. The common risk factors identified within this systematic review provide a minimum list of variables, which future studies should address. Research in this area would benefit from prospective, multi-site studies with larger cohorts as well as the subsequent internal and external validation of predictive models. Ultimately, the ability to identify patients at high risk of post-transplant AKI may enable early intervention and perhaps prevention. PMID:27029658

  20. Acute cardio-renal syndrome: progression from congestive heart failure to congestive kidney failure.

    PubMed

    Wencker, Detlef

    2007-09-01

    Over the past few years, acute worsening of renal function has emerged as a powerful and independent predictor of adverse cardiac outcomes among patients hospitalized with acute heart failure exacerbation. This phenomenon has been recently termed acute cardio-renal syndrome. Acute cardio-renal syndrome is not uncommon, affecting roughly one third of acute decompensated heart failure patients. The mechanism of acute cardio-renal syndrome is poorly understood and difficult to elucidate in light of the complex and multifactorial comorbidities associated with acute heart failure syndrome. Acute cardio-renal syndrome is commonly explained by hypoperfusion of the kidney with intravascular volume depletion, hypotension and low flow state ("pre-renal syndrome"). This perception, however, is challenged by the actual hemodynamics present during acute cardio-renal syndrome characterized by hypervolemia, normal cardiac output, and elevated filling pressures of the systemic and venous circulation. This review discusses the long-standing and unnoticed evidence in support of the notion that right-sided failure with raised filling pressure of the renal vein by itself can indeed lead to acute worsening renal function with oliguria, azotemia, and reduced glomerular filtration rate.

  1. The role of the uncertainty of measurement of serum creatinine concentrations in the diagnosis of acute kidney injury.

    PubMed

    Kin Tekce, Buket; Tekce, Hikmet; Aktas, Gulali; Uyeturk, Ugur

    2016-01-01

    Uncertainty of measurement is the numeric expression of the errors associated with all measurements taken in clinical laboratories. Serum creatinine concentration is the most common diagnostic marker for acute kidney injury. The goal of this study was to determine the effect of the uncertainty of measurement of serum creatinine concentrations on the diagnosis of acute kidney injury. We calculated the uncertainty of measurement of serum creatinine according to the Nordtest Guide. Retrospectively, we identified 289 patients who were evaluated for acute kidney injury. Of the total patient pool, 233 were diagnosed with acute kidney injury using the AKIN classification scheme and then were compared using statistical analysis. We determined nine probabilities of the uncertainty of measurement of serum creatinine concentrations. There was a statistically significant difference in the number of patients diagnosed with acute kidney injury when uncertainty of measurement was taken into consideration (first probability compared to the fifth p = 0.023 and first probability compared to the ninth p = 0.012). We found that the uncertainty of measurement for serum creatinine concentrations was an important factor for correctly diagnosing acute kidney injury. In addition, based on the AKIN classification scheme, minimizing the total allowable error levels for serum creatinine concentrations is necessary for the accurate diagnosis of acute kidney injury by clinicians.

  2. GDF11 improves tubular regeneration after acute kidney injury in elderly mice

    PubMed Central

    Zhang, Ying; Li, Qinggang; Liu, Dong; Huang, Qi; Cai, Guangyan; Cui, Shaoyuan; Sun, Xuefeng; Chen, Xiangmei

    2016-01-01

    The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia–reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2′-deoxyuridine (EdU)-positive proximal tubular epithelial cells. GDF11 improved the renal repair, recovery of renal function, and survival of elderly mice at 72 h after IRI. Moreover, the addition of recombinant GDF11 to primary renal epithelial cells increased proliferation, migration, and dedifferentiation by upregulating the ERK1/2 pathway in vitro. Our study indicates that GDF11/8 in the kidney decreases with age and that GDF11 can increase tubular cell dedifferentiation and proliferation as well as improve tubular regeneration after acute kidney injury (AKI) in old mice. PMID:27703192

  3. Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury

    PubMed Central

    Cocchiaro, Pasquale; Fox, Christopher; Tregidgo, Nicholas W.; Howarth, Rachel; Wood, Katrina M.; Situmorang, Gerhard R.; Pavone, Luigi M.; Sheerin, Neil S.; Moles, Anna

    2016-01-01

    Acute kidney injury (AKI) is an abrupt reduction in kidney function caused by different pathological processes. It is associated with a significant morbidity and mortality in the acute phase and an increased risk of developing End Stage Renal Disease. Despite the progress in the management of the disease, mortality rates in the last five decades remain unchanged at around 50%. Therefore there is an urgent need to find new therapeutic strategies to treat AKI. Lysosomal proteases, particularly Cathepsin D (CtsD), play multiple roles in apoptosis however, their role in AKI is still unknown. Here we describe a novel role for CtsD in AKI. CtsD expression was upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion (IRI) induced AKI. CtsD inhibition using Pepstatin A led to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or IRI induced AKI. Pepstatin A treatment slowed interstitial fibrosis progression following IRI induced AKI. Renal transplant biopsies with acute tubular necrosis demonstrated high levels of CtsD in damaged tubular cells. These results support a role for CtsD in apoptosis during AKI opening new avenues for the treatment of AKI by targeting lysosomal proteases. PMID:27271556

  4. The effect of cytomegalovirus infection on acute rejection in kidney transplanted patients

    PubMed Central

    Hasanzamani, Boshra; Hami, Maryam; Zolfaghari, Vajihe; Torkamani, Mahtab; Ghorban Sabagh, Mahin; Ahmadi Simab, Saiideh

    2016-01-01

    Introduction: It is known that cytomegalovirus (CMV) infection is a common problem among kidney transplant patients. This infection can be increased morbidity and decreased graft survival. This problem has been associated with acute rejection too. Patients and Methods: One hundred and thirty renal transplant patients were included in a prospective, case-control study. The renal transplant patients were divided into two groups; patients group with CMV infection and control group without CMV infection. Serum CMV-IgG in all patients was positive (donor and recipients). None of patients had received anti-thymocyte-globulin and thymoglobulin. CMV infection was diagnosed by quantitative CMV-PCR (polymerase chain reaction) test (more than 500 copies/μg). Rejection episode was defined by kidney isotope scan or biopsy. Results: In the group of 66 CMV infection patients (41 male [62.1%] and 25 female [37.9%]) the incidence of graft rejection was 36%, however in the group of 64 control patients the incidence of graft rejection was 9.4 % (P < 0.005). Conclusion: CMV infection is important predisposing factor for acute allograft rejection after kidney transplantation. The results of this study suggests that the control of CMV infection could decrease episodes of acute kidney rejection. PMID:27471740

  5. Acute renal failure potentiates methylmalonate-induced oxidative stress in brain and kidney of rats.

    PubMed

    Schuck, P F; Alves, L; Pettenuzzo, L F; Felisberto, F; Rodrigues, L B; Freitas, B W; Petronilho, F; Dal-Pizzol, F; Streck, E L; Ferreira, G C

    2013-03-01

    Tissue methylmalonic acid (MMA) accumulation is the biochemical hallmark of methylmalonic acidemia. The disease is clinically characterized by progressive neurological deterioration and kidney failure, whose pathophysiology is still unclear. In the present work we investigated the effects of acute MMA administration on various parameters of oxidative stress in cerebral cortex and kidney of young rats, as well as the influence of acute renal failure on MMA-elicited effects on these parameters. Acute renal failure was induced by gentamicin, an aminoglycoside antibiotic whose utilization over prolonged periods causes nephrotoxicity. The administration of gentamicin alone increased carbonyl content and inhibited superoxide dismutase (SOD) activity in cerebral cortex, as well as increased thiobarbituric acid-reactive substances (TBA-RS) and sulfhydryl levels and diminished glutathione peroxidase activity in kidney. On the other hand, MMA administration increased TBA-RS levels in cerebral cortex and decreased SOD activity in kidney. Furthermore, the simultaneous administration of MMA and gentamicin to the rats provoked an augment in TBA-RS levels and superoxide generation in cerebral cortex and in TBA-RS, carbonyl and sulfhydryl levels in kidney, while diminished SOD activity in both studied tissues. Finally, nitrate/nitrite content, reduced glutathione levels, 2',7'-dihydrodichlorofluorescein oxidation and catalase activity were not affected by this animal treatment in either tissue. In conclusion, our present data are in line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on oxidative stress parameters in brain and peripheral tissues.

  6. Cholestatic jaundice, acute kidney injury and acute pancreatitis secondary to the recreational use of methandrostenolone: a case report

    PubMed Central

    2011-01-01

    Introduction Over the last few years the use of anabolic steroids has become increasingly common amongst amateur athletes and for aesthetic purposes. As a result, the adverse events related to their use are being seen more frequently. Methandrostenolone is an anabolic steroid which is widely available and has been used for both performance enhancement and aesthetic purposes. This drug has also been reported to cause cholestasis of the intra-hepatic bile ducts resulting in elevated aminotransferases, hyperbilirubinemia and clinical jaundice. However, to the best of our knowledge this agent has not been previously reported to cause pancreatitis or acute kidney injury. Case presentation In this paper, we report the case of a 50-year-old man of Indian descent who presented with a six week history of diffuse abdominal pain, anorexia and weight loss following an eight week cycle of methandrostenolone use. At initial presentation, his lipase level was 785 U/L, bilirubin was 922 μmol/L and creatinine was 200 U/L while his aspartate aminotransferase and alanine aminotransferase levels were only mildly elevated at 61 U/L and 56 U/L respectively. His lipase peaked on day nine at >3000 U/L whilst his creatinine level was 299 U/L. Imaging was consistent with acute pancreatitis while a liver biopsy was consistent with intra-hepatic cholestasis and a kidney biopsy revealed evidence of acute tubular necrosis. Conclusion Both acute pancreatitis and acute kidney injury have rarely been reported with anabolic steroid use and they have not been previously reported to occur in the same patient. This case demonstrates some potentially new and serious adverse consequences occurring with the use of anabolic steroids, of which physicians need to be aware. PMID:21470406

  7. Increase of peripheral type benzodiazepine binding sites in kidney and olfactory bulb in acutely stressed rats.

    PubMed

    Novas, M L; Medina, J H; Calvo, D; De Robertis, E

    1987-03-17

    Fifteen minutes after the initiation of swimming stress in the rat we observed a 50% increase in the number of [3H]RO 5-4864 binding sites in kidney and a 37% increase in the olfactory bulb, without change in affinity. The binding in heart and cerebral cortex remained unchanged after the stress. These results are discussed in relation to previous work on both the action of an acute stress in central benzodiazepine receptors and the possible modulation of peripheral benzodiazepine receptors of the kidney by adrenocortical hormones.

  8. Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay

    PubMed Central

    Ogura, Makoto; Kagami, Shino; Nakao, Masatsugu; Kono, Midori; Kanetsuna, Yukiko; Hosoya, Tatsuo

    2012-01-01

    We describe two cases of fungal granulomatous interstitial nephritis (GIN) presenting as acute kidney injury (AKI). Increased serum creatinine was detected in Patient 1 after chemotherapy for pharyngeal cancer and in Patient 2 after steroid pulse therapy for bronchial asthma. Renal histology of both patients revealed GIN. Polymerase chain reaction (PCR)-based detection of fungal DNA sequences from kidney tissue demonstrated Trichosporon laibachii and Candida albicans, respectively. When AKI occurs in an immunocompromised host, differential diagnosis of fungal interstitial nephritis should be considered. Furthermore, PCR-based detection of fungal DNA sequences from renal specimens can be useful for rapid diagnosis. PMID:23936627

  9. Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay.

    PubMed

    Ogura, Makoto; Kagami, Shino; Nakao, Masatsugu; Kono, Midori; Kanetsuna, Yukiko; Hosoya, Tatsuo

    2012-10-01

    We describe two cases of fungal granulomatous interstitial nephritis (GIN) presenting as acute kidney injury (AKI). Increased serum creatinine was detected in Patient 1 after chemotherapy for pharyngeal cancer and in Patient 2 after steroid pulse therapy for bronchial asthma. Renal histology of both patients revealed GIN. Polymerase chain reaction (PCR)-based detection of fungal DNA sequences from kidney tissue demonstrated Trichosporon laibachii and Candida albicans, respectively. When AKI occurs in an immunocompromised host, differential diagnosis of fungal interstitial nephritis should be considered. Furthermore, PCR-based detection of fungal DNA sequences from renal specimens can be useful for rapid diagnosis.

  10. Management of Acute Kidney Injury and Acid-Base Balance in the Septic Patient.

    PubMed

    Weyker, Paul D; Pérez, Xosé L; Liu, Kathleen D

    2016-06-01

    Acute kidney injury (AKI) is an abrupt decrease in kidney function that takes place over hours to days. Sepsis is the leading cause of AKI and portends a particularly high morbidity and mortality, although the severity may vary from a transient rise in serum creatinine to end-stage renal disease. With regard to acid-base management in septic AKI, caution should be used with hyperchloremic crystalloid solutions, and dialysis is often used in the setting of severe acidosis. In the future, biomarkers may help clinicians identify AKI earlier and allow for potential interventions before the development of severe AKI. PMID:27229644

  11. A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery

    PubMed Central

    Pannu, Neesh; Graham, Michelle; Klarenbach, Scott; Meyer, Steven; Kieser, Teresa; Hemmelgarn, Brenda; Ye, Feng; James, Matthew

    2016-01-01

    Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer–Lemeshow goodness-of-fit test and Net Reclassification Improvement index. Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00–4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15–2.40), diabetes mellitus (1.61, 1.12–2.31), baseline estimated glomerular filtration rate (0.96, 0.95–0.97), increasing hemoglobin concentration (0.85, 0.77–0.93), proteinuria (1.65, 1.07–2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64–2.43), other cardiac procedure (v. CABG only, 3.11, 2.12–4.58) and emergent status for surgery booking (4.63, 2.61–8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79–0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). Interpretation: We have developed

  12. Changes in Metabolic Profiles during Acute Kidney Injury and Recovery following Ischemia/Reperfusion

    PubMed Central

    Wei, Qingqing; Xiao, Xiao; Fogle, Paul; Dong, Zheng

    2014-01-01

    Changes of metabolism have been implicated in renal ischemia/reperfusion injury (IRI). However, a global analysis of the metabolic changes in renal IRI is lacking and the association of the changes with ischemic kidney injury and subsequent recovery are unclear. In this study, mice were subjected to 25 minutes of bilateral renal IRI followed by 2 hours to 7 days of reperfusion. Kidney injury and subsequent recovery was verified by serum creatinine and blood urea nitrogen measurements. The metabolome of plasma, kidney cortex, and medulla were profiled by the newly developed global metabolomics analysis. Renal IRI induced overall changes of the metabolome in plasma and kidney tissues. The changes started in renal cortex, followed by medulla and plasma. In addition, we identified specific metabolites that may contribute to early renal injury response, perturbed energy metabolism, impaired purine metabolism, impacted osmotic regulation and the induction of inflammation. Some metabolites, such as 3-indoxyl sulfate, were induced at the earliest time point of renal IRI, suggesting the potential of being used as diagnostic biomarkers. There was a notable switch of energy source from glucose to lipids, implicating the importance of appropriate nutrition supply during treatment. In addition, we detected the depressed polyols for osmotic regulation which may contribute to the loss of kidney function. Several pathways involved in inflammation regulation were also induced. Finally, there was a late induction of prostaglandins, suggesting their possible involvement in kidney recovery. In conclusion, this study demonstrates significant changes of metabolome kidney tissues and plasma in renal IRI. The changes in specific metabolites are associated with and may contribute to early injury, shift of energy source, inflammation, and late phase kidney recovery. PMID:25191961

  13. Programmatic Implications of Acute and Early HIV Infection.

    PubMed

    Suthar, Amitabh B; Granich, Reuben M; Kato, Masaya; Nsanzimana, Sabin; Montaner, Julio S G; Williams, Brian G

    2015-11-01

    Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and late stages. Acute HIV infection lasts approximately 3 weeks and early HIV infection, which includes acute HIV infection, lasts approximately 7 weeks. Many testing and blood screening algorithms detect HIV antibodies about 3 weeks after HIV infection. Incidence estimates are based on results of modeling, cohort studies, surveillance, and/or assays. Viral load is the key modifiable risk factor for HIV transmission and peaks during acute and early HIV infection. Empirical evidence characterizing the impact of acute and early HIV infection on the spread of the HIV epidemic are limited. Time trends of HIV prevalence collected from concentrated and generalized epidemics suggest that acute and early HIV infection may have a limited role in population HIV transmission. Collectively, these data suggest that acute and early HIV infection is relatively short and does not currently require fundamentally different programmatic approaches to manage the HIV/AIDS epidemic in most settings. Research and surveillance will inform which epidemic contexts and phases may require tailored strategies for these stages of HIV infection.

  14. Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury

    PubMed Central

    2008-01-01

    BACKGROUND The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial. METHODS We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. RESULTS Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P = 0.47). There was no significant difference between the two groups in the duration of renalreplacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. CONCLUSIONS Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal

  15. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway.

    PubMed

    Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Youjia; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

    2014-04-01

    Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes.

  16. Treatment disparities in acute coronary syndromes, heart failure, and kidney disease.

    PubMed

    McCullough, Peter A; Maynard, Robert C

    2011-01-01

    It has been consistently observed that patients with renal dysfunction have more premature, severe, complicated, and fatal cardiovascular disease than age- and sex-matched individuals with normal renal function. There have been 4 major explanations for this finding: (1) positive confounding by third variables associated with chronic kidney disease (CKD), including diabetes mellitus and hypertension; (2) therapeutic nihilism or lesser use of beneficial therapies in CKD; (3) greater toxicities of therapies, such as bleeding from anticoagulants or contrast-induced kidney injury; (4) biological factors which result directly from CKD that work to promote and accelerate cardiovascular disease. In this paper, we focus on the issue of treatment disparities or therapeutic nihilism and its contribution to poor outcomes in the setting of acute coronary syndromes and acutely decompensated heart failure. This issue is important because if we can overcome barriers to the utilization of beneficial treatments, then clinical outcomes should improve over time.

  17. Treatment disparities in acute coronary syndromes, heart failure, and kidney disease.

    PubMed

    McCullough, Peter A; Maynard, Robert C

    2011-01-01

    It has been consistently observed that patients with renal dysfunction have more premature, severe, complicated, and fatal cardiovascular disease than age- and sex-matched individuals with normal renal function. There have been 4 major explanations for this finding: (1) positive confounding by third variables associated with chronic kidney disease (CKD), including diabetes mellitus and hypertension; (2) therapeutic nihilism or lesser use of beneficial therapies in CKD; (3) greater toxicities of therapies, such as bleeding from anticoagulants or contrast-induced kidney injury; (4) biological factors which result directly from CKD that work to promote and accelerate cardiovascular disease. In this paper, we focus on the issue of treatment disparities or therapeutic nihilism and its contribution to poor outcomes in the setting of acute coronary syndromes and acutely decompensated heart failure. This issue is important because if we can overcome barriers to the utilization of beneficial treatments, then clinical outcomes should improve over time. PMID:21625092

  18. Epidemiology of acute infections among patients with chronic kidney disease.

    PubMed

    Dalrymple, Lorien S; Go, Alan S

    2008-09-01

    The objectives of this review were (1) to review recent literature on the rates, risk factors, and outcomes of infections in patients who had chronic kidney disease (CKD) and did or did not require renal replacement therapy; (2) to review literature on the efficacy and use of selected vaccines for patients with CKD; and (3) to outline a research framework for examining key issues regarding infections in patients with CKD. Infection-related hospitalizations contribute substantially to excess morbidity and mortality in patients with ESRD, and infection is the second leading cause of death in this population. Patients who have CKD and do not require renal replacement therapy seem to be at higher risk for infection compared with patients without CKD; however, data about patients who have CKD and do not require dialysis therapy are very limited. Numerous factors potentially predispose patients with CKD to infection: advanced age, presence of coexisting illnesses, vaccine hyporesponsiveness, immunosuppressive therapy, uremia, dialysis access, and the dialysis procedure. Targeted vaccination seems to have variable efficacy in the setting of CKD and is generally underused in this population. In conclusion, infection is a primary issue when caring for patients who receive maintenance dialysis. Very limited data exist about the rates, risk factors, and outcomes of infection in patients who have CKD and do not require dialysis. Future research is needed to delineate accurately the epidemiology of infections in these populations and to develop effective preventive strategies across the spectrum of CKD severity. PMID:18650409

  19. Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning

    PubMed Central

    Dhanapriya, J.; Gopalakrishnan, N.; Arun, V.; Dineshkumar, T.; Sakthirajan, R.; Balasubramaniyan, T.; Haris, M.

    2016-01-01

    Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI) and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC). Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months. PMID:27194836

  20. An unexpected cause of acute kidney injury in a patient with ANCA associated vasculitis.

    PubMed

    Choudhry, Wajid M; Nori, Uday S; Nadasdy, Tibor; Satoskar, Anjali A

    2016-05-01

    Diagnostic kidney biopsies sometimes yield clinically unsuspected diagnoses. We present a case of a 69-year-old woman with established ANCA-associated vasculitis (AAV) of 4 years duration who was in clinical remission following cytotoxic therapy and was on maintenance immunosuppression. She presented to the hospital with acute kidney injury (AKI), symptoms suggestive of a systemic vasculitis, and in addition had hypercalcemia, metabolic alkalosis. A relapse in the AAV was suspected but a diagnostic kidney biopsy showed acute tubular necrosis, patchy interstitial inflammation, and calcium phosphate deposits. It was found that the patient recently started consuming large doses of over-the-counter calcium-containing antacids and vitamin Dcontaining multivitamin supplements. Cessation of these drugs led to improvement of renal function to baseline. This case highlights several teaching points: (1) the kidney biopsy can prove to be critically important even in cases where there appears to be a more obvious clinical diagnosis, (2) AK due to calcium-alkali syndrome has characteristic histopathological changes, and (3) that the triad of hypercalcemia, metabolic alkalosis, and AKI is exclusively associated with the ingestion of excessive quantities of calcium-containing antacids. The physician should keep this in mind, and pro-actively seek pertinent medication history from the patient. A brief review of calcium-alkali syndrome is given.

  1. An unexpected cause of acute kidney injury in a patient with ANCA associated vasculitis.

    PubMed

    Choudhry, Wajid M; Nori, Uday S; Nadasdy, Tibor; Satoskar, Anjali A

    2016-05-01

    Diagnostic kidney biopsies sometimes yield clinically unsuspected diagnoses. We present a case of a 69-year-old woman with established ANCA-associated vasculitis (AAV) of 4 years duration who was in clinical remission following cytotoxic therapy and was on maintenance immunosuppression. She presented to the hospital with acute kidney injury (AKI), symptoms suggestive of a systemic vasculitis, and in addition had hypercalcemia, metabolic alkalosis. A relapse in the AAV was suspected but a diagnostic kidney biopsy showed acute tubular necrosis, patchy interstitial inflammation, and calcium phosphate deposits. It was found that the patient recently started consuming large doses of over-the-counter calcium-containing antacids and vitamin Dcontaining multivitamin supplements. Cessation of these drugs led to improvement of renal function to baseline. This case highlights several teaching points: (1) the kidney biopsy can prove to be critically important even in cases where there appears to be a more obvious clinical diagnosis, (2) AK due to calcium-alkali syndrome has characteristic histopathological changes, and (3) that the triad of hypercalcemia, metabolic alkalosis, and AKI is exclusively associated with the ingestion of excessive quantities of calcium-containing antacids. The physician should keep this in mind, and pro-actively seek pertinent medication history from the patient. A brief review of calcium-alkali syndrome is given. PMID:26932179

  2. Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities

    PubMed Central

    Yu, Chen; Qi, Dong; Sun, Ju-Feng; Li, Peng; Fan, Hua-Ying

    2015-01-01

    This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury. PMID:26149595

  3. Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities.

    PubMed

    Yu, Chen; Qi, Dong; Sun, Ju-Feng; Li, Peng; Fan, Hua-Ying

    2015-07-07

    This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.

  4. Statins for the prevention of contrast-induced acute kidney injury.

    PubMed

    Ball, Timothy; McCullough, Peter A

    2014-01-01

    Acute kidney injury (AKI) is a common medical problem, especially in patients undergoing cardiovascular procedures. The risk of kidney damage has multiple determinants and is often related to or exacerbated by intravenous or intra-arterial iodinated contrast. Contrast-induced AKI (CI-AKI) has been associated with an increased risk of subsequent myocardial infarction, stroke, the development of heart failure, rehospitalization, progression of chronic kidney disease, end-stage renal disease, and death. Statins have been studied extensively in the setting of chronic kidney disease and they have been shown to reduce albuminuria, but they have had no effect on the progressive reduction of glomerular filtration or the need for renal replacement therapy. Several meta-analyses have shown a protective effect of short-term statin administration on CI-AKI and led to two large randomized controlled trials evaluating the role of rosuvastatin in the prevention of CI-AKI in high-risk patients with acute coronary syndrome and diabetes mellitus. Both trials showed a benefit of rosuvastatin prior to contrast administration in a statin-naive patient population. In aggregate, these studies support the short-term use of statins specifically for the prevention of CI-AKI in patients undergoing coronary angiography with or without percutaneous coronary intervention. PMID:25343843

  5. Timing is everything? Reconciling the results of recent trials in acute kidney injury.

    PubMed

    Wyatt, Christina M; Coca, Steven G

    2016-10-01

    Observational studies have failed to establish the optimal timing of renal replacement therapy in critically ill adults with acute kidney injury, with some studies suggesting benefit and others suggesting the potential for harm with earlier initiation. Two recent randomized trials have addressed this controversy, also with conflicting results. Careful consideration of differences between the 2 studies is essential when applying the results to clinical practice in the intensive care unit. PMID:27575558

  6. Sympathomimetic syndrome, choreoathetosis, and acute kidney injury following "bath salts" injection.

    PubMed

    Sutamtewagul, Grerk; Sood, Vineeta; Nugent, Kenneth

    2014-01-01

    "Bath salts" is a well known street drug which can cause several cardiovascular and neuropsychiatric symptoms. However, only one case of acute kidney injury has been reported in the literature. We present a case with sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury following the use of bath salts. A 37-year-old man with past medical history of hypertension and depression was brought to the emergency center with body shaking. Three days before admission he injected 3 doses of bath salts intravenously and felt eye pain with blurry vision followed by a metallic taste, strange smells, profuse sweating, and body shaking. At presentation he had a sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea, and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of 15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved his symptoms and his renal failure. Bath salts contain 3,4-methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake inhibitor. Choreoathetosis in this patient could be explained through dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for acute kidney injury from bath salts may involve direct drug effects though norepinephrine and dopamine-induced vasoconstriction (renal ischemia), rhabdomyolysis, hyperthermia, and/or volume contraction. PMID:24356039

  7. Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury.

    PubMed

    Lankadeva, Yugeesh R; Kosaka, Junko; Evans, Roger G; Bailey, Simon R; Bellomo, Rinaldo; May, Clive N

    2016-07-01

    Norepinephrine is the principal vasopressor used to restore blood pressure in sepsis, but its effects on intrarenal oxygenation are unknown. To clarify this, we examined renal cortical, medullary, and urinary oxygenation in ovine septic acute kidney injury and the response to resuscitation with norepinephrine. A renal artery flow probe and fiberoptic probes were placed in the cortex and medulla of sheep to measure tissue perfusion and oxygenation. A probe in the bladder catheter measured urinary oxygenation. Sepsis was induced in conscious sheep by infusion of Escherichia coli for 32 hours. At 24 to 30 hours of sepsis, either norepinephrine, to restore mean arterial pressure to preseptic levels or vehicle-saline was infused (8 sheep per group). Septic acute kidney injury was characterized by a reduction in blood pressure of ∼12 mm Hg, renal hyperperfusion, and oliguria. Sepsis reduced medullary perfusion (from an average of 1289 to 628 blood perfusion units), medullary oxygenation (from 32 to 16 mm Hg), and urinary oxygenation (from 36 to 24 mm Hg). Restoring blood pressure with norepinephrine further reduced medullary perfusion to an average of 331 blood perfusion units, medullary oxygenation to 8 mm Hg and urinary oxygenation to 18 mm Hg. Cortical perfusion and oxygenation were preserved. Thus, renal medullary hypoxia caused by intrarenal blood flow redistribution may contribute to the development of septic acute kidney injury, and resuscitation of blood pressure with norepinephrine exacerbates medullary hypoxia. The parallel changes in medullary and urinary oxygenation suggest that urinary oxygenation may be a useful real-time biomarker for risk of acute kidney injury. PMID:27165831

  8. Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure.

    PubMed

    Porubsky, Stefan; Federico, Giuseppina; Müthing, Johannes; Jennemann, Richard; Gretz, Norbert; Büttner, Stefan; Obermüller, Nicholas; Jung, Oliver; Hauser, Ingeborg A; Gröne, Elisabeth; Geiger, Helmut; Gröne, Hermann-Josef; Betz, Christoph

    2014-09-01

    The pathogenesis and therapy of Shigatoxin 2 (Stx2)-mediated kidney failure remain controversial. Our aim was to test whether, during an infection with Stx2-producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium and thereby possibly contributes to acute renal failure. Mice represent a suitable model because they, like humans, express the Stx2-receptor Gb3 in the tubular epithelium but, in contrast to humans, not in glomerular endothelia, and are thus free of glomerular thrombotic microangiopathy (TMA). In wild-type mice, Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance, which was most likely the cause of death. Tubule-specific depletion of Gb3 protected the mice from acute renal failure. In vitro, Stx2 induced secretion of proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus implicating a direct effect of Stx2 on the tubular epithelium. To correlate these results to human disease, kidney biopsies and outcome were analysed in patients with Stx2-associated kidney failure (n = 11, aged 22-44 years). The majority of kidney biopsies showed different stages of an ongoing TMA; however, no glomerular complement activation could be demonstrated. All biopsies, including those without TMA, showed severe acute tubular damage. Due to these findings, patients were treated with supportive therapy without complement-inhibiting antibodies (eculizumab) or immunoadsorption. Despite the severity of the initial disease [creatinine 6.34 (1.31-17.60) mg/dl, lactate dehydrogenase 1944 (753-2792) U/l, platelets 33 (19-124)/nl and haemoglobin 6.2 (5.2-7.8) g/dl; median (range)], all patients were discharged after 33 (range 19-43) days with no neurological symptoms and no dialysis requirement [creatinine 1.39 (range 0.84-2.86) mg/dl]. The creatinine decreased further to 0.90 (range 0.66-1.27) mg/dl after 24 months. Based on these data, one may surmise that acute tubular damage represents a separate

  9. [Star fruit as a cause of acute kidney injury].

    PubMed

    Scaranello, Karilla Lany; Alvares, Valeria Regina de Cristo; Carneiro, Daniely Maria Queiroz; Barros, Flávio Henrique Soares; Gentil, Thais Marques Sanches; Thomaz, Myriam José; Pereira, Benedito Jorge; Pereira, Mariana Batista; Leme, Graziella Malzoni; Diz, Mary Carla Esteves; Laranja, Sandra Maria Rodrigues

    2014-01-01

    The star fruit belongs to the family Oxalidacea, species Averrhoa carambola. It is rich in minerals, vitamin A, C, B complex vitamins and oxalic acid. Recent studies show that the toxicity of the fruit differs between the patients and may be explained by single biological responses, age, and the intake quantity of the neurotoxin in each fruit in addition to glomerular filtration rate given by each patient. Additionally, the nephrotoxicity caused by the fruit is dose-dependent and may lead to the deposition of crystals of calcium oxalate intratubular, as well as by direct injury to the renal tubular epithelium, leading to apoptosis of the same. We report the case of a patient who after ingestion of the juice and fresh fruit, developed acute renal failure requiring dialysis, evolving with favourable outcome and recovery of renal function.

  10. Progression of Chronic Kidney Disease After Acute Kidney Injury: Role of Self-Perpetuating Versus Hemodynamic-Induced Fibrosis.

    PubMed

    Picken, Maria; Long, Jianrui; Williamson, Geoffrey A; Polichnowski, Aaron J

    2016-10-01

    The relative contribution of self-perpetuating versus hemodynamic-induced fibrosis to the progression of chronic kidney disease (CKD) after acute kidney injury (AKI) is unclear. In the present study, male Sprague-Dawley rats underwent right uninephrectomy and were instrumented with a blood pressure radiotelemeter. Two weeks later, separate groups of rats were subjected to 40 minutes renal ischemia-reperfusion or sham surgery and followed up for 4 or 16 weeks to determine the extent to which glomerulosclerosis and tubulointerstitial fibrosis as a result of the AKI-CKD transition (ie, at 4 weeks post AKI) change over time during the progression of CKD (ie, at 16 weeks post AKI). On average, tubulointerstitial fibrosis was ≈3-fold lower (P<0.05), whereas glomerulosclerosis was ≈6-fold higher (P<0.05) at 16 versus 4 weeks post AKI. At 16 weeks post AKI, marked tubulointerstitial fibrosis was only observed in rats exhibiting marked glomerulosclerosis, proteinuria, and kidney hypertrophy consistent with a hemodynamic pathogenesis of renal injury. Moreover, quantitative analysis between blood pressure and renal injury revealed a clear and modest blood pressure threshold (average 16-week systolic blood pressure of ≈127 mm Hg) for the development of glomerulosclerosis. In summary, modest levels of blood pressure may be playing a substantial role in the progression of renal disease after AKI in settings of preexisting CKD associated with 50% loss of renal mass. In contrast, these data do not support a major role of self-perpetuating tubulointerstitial fibrosis in the progression CKD after AKI in such settings. PMID:27550923

  11. Contrast-induced acute kidney injury: short- and long-term implications.

    PubMed

    Weisbord, Steven D; Palevsky, Paul M

    2011-05-01

    The intravascular administration of iodine-based contrast media remains a common cause of acute kidney injury and a leading cause of iatrogenic renal disease. Past research has elucidated the principal risk factors for contrast-induced acute kidney injury (CIAKI) and helped to establish the efficacy of various interventions for the prevention of this condition. The importance of preventing CIAKI has been underscored by a growing number of studies showing strong associations of CIAKI with serious adverse short- and long-term outcomes. However, it remains unclear whether these associations are causal. This is important because considerable health care resources are used to prevent CIAKI. If CIAKI is a marker, but not a mediator, of serious adverse downstream outcomes, more judicious and selective use of preventive care may be appropriate. Moreover, with an increasing number of studies reporting the underuse of coronary angiography in patients with acute coronary syndrome and underlying chronic kidney disease, presumably in part because of a fear of CIAKI, a clear understanding of whether this condition directly results in adverse downstream outcomes is essential. Careful inspection of past studies that investigated the association of CIAKI with adverse short- and long-term events sheds light on their strengths and weaknesses and provides insight into how future research may be better able to characterize the short- and long-term implications of this iatrogenic condition.

  12. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage.

    PubMed

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  13. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

    PubMed Central

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S.; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  14. Acute kidney injury induced by antimicrobial agents in the elderly: awareness and mitigation strategies.

    PubMed

    Mizokami, Fumihiro; Mizuno, Tomohiro

    2015-01-01

    The use of antimicrobial agents has increased in recent years as treatments have diversified and resistant bacteria have appeared. With increased use of antimicrobial agents, elderly patients are prone to adverse drug reactions (ADRs) as a result of factors such as drug-drug interactions, polypharmacy, long-term use, and over- or under-dosage. In particular, elderly patients using antimicrobials are at increased risk to develop drug-induced acute kidney injury (AKI), which is the most common severe ADR in such patients. AKI is a serious problem that is associated with mortality amongst hospitalized patients. Antimicrobial-induced AKI can be classified into three different types: acute tubular necrosis (ATN), acute interstitial nephritis (AIN), and renal tubule lumen obstruction. AKI can generally be prevented by proper maintenance of fluid balance. To design dosage regimens that ensure efficient drug excretion via the kidney, it is necessary to accurately estimate renal function; however, the kidney undergoes age-dependent structural and functional alterations over time. Therefore, proper management of antimicrobial agents by an antimicrobial stewardship team may lead to decreased incidence of AKI. This article reviews antimicrobial-induced AKI and discusses potential strategies for increasing awareness of AKI and mitigating its clinical effects.

  15. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.

    PubMed

    Arai, Satoko; Kitada, Kento; Yamazaki, Tomoko; Takai, Ryosuke; Zhang, Xizhong; Tsugawa, Yoji; Sugisawa, Ryoichi; Matsumoto, Ayaka; Mori, Mayumi; Yoshihara, Yasunori; Doi, Kent; Maehara, Natsumi; Kusunoki, Shunsuke; Takahata, Akiko; Noiri, Eisei; Suzuki, Yusuke; Yahagi, Naoki; Nishiyama, Akira; Gunaratnam, Lakshman; Takano, Tomoko; Miyazaki, Toru

    2016-02-01

    Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI. PMID:26726878

  16. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.

    PubMed

    Arai, Satoko; Kitada, Kento; Yamazaki, Tomoko; Takai, Ryosuke; Zhang, Xizhong; Tsugawa, Yoji; Sugisawa, Ryoichi; Matsumoto, Ayaka; Mori, Mayumi; Yoshihara, Yasunori; Doi, Kent; Maehara, Natsumi; Kusunoki, Shunsuke; Takahata, Akiko; Noiri, Eisei; Suzuki, Yusuke; Yahagi, Naoki; Nishiyama, Akira; Gunaratnam, Lakshman; Takano, Tomoko; Miyazaki, Toru

    2016-02-01

    Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.

  17. Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies).

    PubMed

    Ichai, Carole; Vinsonneau, Christophe; Souweine, Bertrand; Armando, Fabien; Canet, Emmanuel; Clec'h, Christophe; Constantin, Jean-Michel; Darmon, Michaël; Duranteau, Jacques; Gaillot, Théophille; Garnier, Arnaud; Jacob, Laurent; Joannes-Boyau, Olivier; Juillard, Laurent; Journois, Didier; Lautrette, Alexandre; Muller, Laurent; Legrand, Matthieu; Lerolle, Nicolas; Rimmelé, Thomas; Rondeau, Eric; Tamion, Fabienne; Walrave, Yannick; Velly, Lionel

    2016-12-01

    Acute kidney injury (AKI) is a syndrome that has progressed a great deal over the last 20 years. The decrease in urine output and the increase in classical renal biomarkers, such as blood urea nitrogen and serum creatinine, have largely been used as surrogate markers for decreased glomerular filtration rate (GFR), which defines AKI. However, using such markers of GFR as criteria for diagnosing AKI has several limits including the difficult diagnosis of non-organic AKI, also called "functional renal insufficiency" or "pre-renal insufficiency". This situation is characterized by an oliguria and an increase in creatininemia as a consequence of a reduction in renal blood flow related to systemic haemodynamic abnormalities. In this situation, "renal insufficiency" seems rather inappropriate as kidney function is not impaired. On the contrary, the kidney delivers an appropriate response aiming to recover optimal systemic physiological haemodynamic conditions. Considering the kidney as insufficient is erroneous because this suggests that it does not work correctly, whereas the opposite is occurring, because the kidney is healthy even in a threatening situation. With current definitions of AKI, normalization of volaemia is needed before defining AKI in order to avoid this pitfall. PMID:27230984

  18. Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury.

    PubMed

    Zhao, Wen-Yu; Zhang, Lei; Sui, Ming-Xing; Zhu, You-Hua; Zeng, Li

    2016-01-01

    Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD(+) dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1β and IL-18. PMID:27620507

  19. Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury

    PubMed Central

    Zhao, Wen-Yu; Zhang, Lei; Sui, Ming-Xing; Zhu, You-Hua; Zeng, Li

    2016-01-01

    Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD+ dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model. SIRT3 deletion increased the CLP-induced upregulation of the NLRP3 inflammasome and apoptosis-associated speck-like protein, resulting in the activation of oxidative stress, increased production of the proinflammatory cytokines interleukin (IL)-1β and IL-18, and the enhancement of apoptosis, and these effects were reversed by antioxidant NAC. Our results suggest that SIRT3 plays a protective role against mitochondrial damage in the kidney by attenuating ROS production, inhibiting the NRLP3 inflammasome, attenuating oxidative stress, and downregulating IL-1β and IL-18. PMID:27620507

  20. Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies).

    PubMed

    Ichai, Carole; Vinsonneau, Christophe; Souweine, Bertrand; Armando, Fabien; Canet, Emmanuel; Clec'h, Christophe; Constantin, Jean-Michel; Darmon, Michaël; Duranteau, Jacques; Gaillot, Théophille; Garnier, Arnaud; Jacob, Laurent; Joannes-Boyau, Olivier; Juillard, Laurent; Journois, Didier; Lautrette, Alexandre; Muller, Laurent; Legrand, Matthieu; Lerolle, Nicolas; Rimmelé, Thomas; Rondeau, Eric; Tamion, Fabienne; Walrave, Yannick; Velly, Lionel

    2016-12-01

    Acute kidney injury (AKI) is a syndrome that has progressed a great deal over the last 20 years. The decrease in urine output and the increase in classical renal biomarkers, such as blood urea nitrogen and serum creatinine, have largely been used as surrogate markers for decreased glomerular filtration rate (GFR), which defines AKI. However, using such markers of GFR as criteria for diagnosing AKI has several limits including the difficult diagnosis of non-organic AKI, also called "functional renal insufficiency" or "pre-renal insufficiency". This situation is characterized by an oliguria and an increase in creatininemia as a consequence of a reduction in renal blood flow related to systemic haemodynamic abnormalities. In this situation, "renal insufficiency" seems rather inappropriate as kidney function is not impaired. On the contrary, the kidney delivers an appropriate response aiming to recover optimal systemic physiological haemodynamic conditions. Considering the kidney as insufficient is erroneous because this suggests that it does not work correctly, whereas the opposite is occurring, because the kidney is healthy even in a threatening situation. With current definitions of AKI, normalization of volaemia is needed before defining AKI in order to avoid this pitfall.

  1. Clinical characteristics and mortality risk prediction in children with acute kidney injury

    PubMed Central

    Sadeghi-Bojd, Simin; Noori, Noor Mohammad; Mohammadi, Mehdi; Teimouri, Alireza

    2015-01-01

    Background: Acute kidney injury (AKI) is characterized by a reversible increase in the blood concentration of creatinine and nitrogenous waste products and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. Objective: AKI is a serious condition in critically ill patients. The aim of the study was to determine incidence rate, identify risk factors, and describe the clinical outcome of AKI in the Pediatric Intensive Care Unit (PICU). Materials and Methods: This prospective observational study was conducted in the PICU of a hospital in the South-east Area of Iran (Zahedan City), to study the clinico-etiological profile of AKI (defined according to the AKI network criteria). Over a period of 20 months from April 2012 to December 2014, 303 children were included in the study. Both the groups of patients, those who developed AKI and those who did not develop AKI, were then followed during the course of their hospital stay. Results: There were 303 cases included in the study, with the incidence rate of AKI of 14.9% in PICU. The most common PICU admission diagnoses in AKI were neurologic 85 (%28.05), followed by heart diseases 52 (17.18%) and 31 (10.23%) for respiratory diseases. AKI was 43.5 and 5.4 times more prevalent in renal and endocrine patients compared to those with heart disease respectively. The mortality rate was estimated to be higher in patients with AKI compared to their counterparts (40% vs. 17.8%). Chance of death increased in patients with AKI (odds ratio = 3.04). Conclusion: AKI is a serious problem, but its true incidence is unknown. Understanding the epidemiology of AKI by using of standard definition help us to find high-risk children that are the first step to improve outcomes. The future multiple-center study may benefit by better identifying risk factors and early detection of AKI by using biomarkers novel to prevent the developing of AKI. PMID:26778883

  2. Effect of the technique for assisting renal blood circulation on ischemic kidney in acute cardiorenal syndrome.

    PubMed

    Hanada, Shigeru; Takewa, Yoshiaki; Mizuno, Toshihide; Tsukiya, Tomonori; Taenaka, Yoshiyuki; Tatsumi, Eisuke

    2012-06-01

    The technique for assisting renal blood circulation may be a useful therapeutic method in acute cardiorenal syndrome (ACRS), because renal ischemic dysfunction due to the reduced renal blood circulation is a powerful negative prognostic factor in ACRS. We constructed a circuit assisting renal arterial pressure and flow, and performed renal-selective blood perfusion (RSP) to the left kidney in a goat model of ACRS induced by right ventricular rapid pacing (n = 8), with the right kidney left intact as an internal control. Upon induction of ACRS, renal arterial flow (RAF), creatinine clearance (CCr), and renal oxygen consumption (RVO(2)) of the left kidney decreased to 49, 48, and 63% of the respective baseline values accompanied by a significant increase in renal vascular resistance (RVR), and similar results were observed in the right kidney. Then, RSP improved RVR and increased left RAF, CCr, and RVO(2) up to 91, 86, and 93% of baseline values, respectively, without a significant change in systemic hemodynamics. The RSP-treated kidney showed significantly higher CCr and urinary excretion of water and sodium compared to the contralateral kidney. Additional infusion of prostaglandin E(1) with RSP decreased RVR further and enabled the left RAF to increase up to 129% of the baseline value, without a significant change in systemic hemodynamic parameters. The CCr and RVO(2) did not change significantly, and urinary excretion of water and sodium showed a tendency to increase. These findings suggest that the technique for assisting renal blood circulation for both kidneys may offer a new treatment strategy for patients with ACRS.

  3. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney Injury: part 2: renal replacement therapy.

    PubMed

    Jörres, Achim; John, Stefan; Lewington, Andrew; ter Wee, Pieter M; Vanholder, Raymond; Van Biesen, Wim; Tattersall, James

    2013-12-01

    This paper provides an endorsement of the KDIGO guideline on acute kidney injury; more specifically, on the part that concerns renal replacement therapy. New evidence that has emerged since the publication of the KDIGO guideline was taken into account, and the guideline is commented on from a European perspective. Advice is given on when to start and stop renal replacement therapy in acute kidney injury; which modalities should be preferentially be applied, and in which conditions; how to gain access to circulation; how to measure adequacy; and which dose can be recommended.

  4. Spectrum of glomerular diseases causing acute kidney injury; 25 years experience from a single center

    PubMed Central

    Naqvi, Rubina; Mubarak, Muhammed; Ahmed, Ejaz; Akhtar, Fazal; Bhatti, Sajid; Naqvi, Anwar; Rizvi, Adib

    2015-01-01

    Introduction: Acute kidney injury (AKI) is common in nephro-urological practice. Its incidence, prevalence and etiology vary widely, mainly due to variations in the definitions of AKI. Objectives: We aim to report the spectrum of glomerular diseases presenting as AKI at a kidney referral center in Pakistan. Patients and Methods: An observational cohort of patients identified as having AKI which was defined according to RIFLE criteria, with normal size, non-obstructed kidneys on ultrasonography, along with active urine sediment, edema and new onset hypertension. Results: From 1990 to 2014, 236 cases of AKI secondary to acute glomerulonephritis (AGN) registered at this institution. Mean age of patients was 27.94± 12.79 years and M:F ratio was 0.77:1. Thirty percent patients revealed crescents on renal biopsy. AGN without crescents was seen in 33.05% of cases. Postinfectious GN was found in 14.4%, lupus nephritis in 8.5% and mesangiocapillary GN in 3.4% cases. Renal replacement therapy (RRT) required in 75.84% patients. Pulse steroids were given in 45.33% cases followed by oral steroids. Pulse cyclophoshphamide was given in 23.7% cases and plasmapheresis was used in 3.38% cases. Complete recovery was seen in 44%, while 11.44% died during acute phase of illness. About 19.49 % developed chronic kidney disease (CKD) and 25.84% were lost to long- term follow-up. Conclusion: Although glomerular diseases contribute only 4.19 % of total AKI at this center, morbidity associated with illness and its treatment is more marked than other AKI groups. Another notable factor is late referral of these patients to specialized centers resulting in undesirable outcome. PMID:26693497

  5. [Acute kidney insufficiency of obstetric origin. Experience at the Santo Tomas Hospital (1966-1981)].

    PubMed

    Díaz, J H; de Gordón, G; Hernández, L; Medina, R

    1990-01-01

    The authors review 24 cases of acute renal failure of obstetric etiology occurred in Hospital Santo Tomás, which represents a frequency of 1.375/10,000, with a bimodal distribution and the main causes were toxemia of pregnancy and sepsis. All cases were of the oliguric type and a kidney biopsy was performed in 17 cases, revealing an acute tubular necrosis in 16 and a diffuse cortical necrosis in the other case. Two patients (8.3%) died and one did not received nephrology treatment as the other 23 patients. The fetal mortality was 37.5% and the Apgar was good in 2, fair in one and bad in 2. A 50% of the complications were infections and nine patients tolerated different surgical procedures after the installation of the acute renal failure. The follow-up of 12 patients shows no evidence of renal failure.

  6. Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) trial: the protocol for a large pilot study

    PubMed Central

    Abdelaziz, Tarek Samy; Lindenmeyer, Antje; Baharani, Jyoti; Mistry, Hema; Sitch, Alice; Temple, R Mark; Perkins, Gavin; Thomas, Mark

    2016-01-01

    Introduction Acute kidney injury (AKI) contributes to morbidity and mortality, and its care is often suboptimal and/or delayed. The Acute Kidney Outreach to Reduce Deterioration and Death (AKORDD) study is a large pilot testing provision of early specialist advice, to improve outcomes for patients with AKI. Methods and analysis This before and after study will test an Outreach service for adult patients with AKI, identified using the national algorithm. During the 2-month before phase, AKI outcomes (30-day mortality, need for dialysis or AKI stage deterioration) will be observed in the intervention and control hospitals and their respective community areas; no interventions will be delivered. Patients will receive good standard care. During the 5-month after phase, the intervention will be delivered to patients with AKI in the intervention hospital and its area. Patients with AKI in the control hospital and its area will continue to have good standard care only. Patients already on dialysis and at end of life will be excluded. The interventions will be initially delivered via a phone call, with or without a visit to the primary clinician, aiming at rapidly establishing the aetiology, correcting reversible causes and conducting further appropriate investigation. Surviving stage 3 patients will be followed-up in an AKI clinic. We will conduct qualitative research using focus group-based discussions with primary and secondary care clinicians during the early and late phases of the trial. This will help break down potential barriers and improve care delivery. Ethics and dissemination Patients will be contacted about the study allowing them to ‘opt out’. The work of an Outreach team, guided by AKI alerts and delivering timely advice to clinicians, may improve outcomes. If the results suggest that benefits are delivered by an AKI Outreach team, this study will lead to a full cluster randomised trial. Trial registration number NCT02398682: Pre-results. PMID:27543592

  7. Transgenic expression of proximal tubule peroxisome proliferator-activated receptor-alpha in mice confers protection during acute kidney injury.

    PubMed

    Li, Shenyang; Nagothu, Kiran K; Desai, Varsha; Lee, Taewon; Branham, William; Moland, Carrie; Megyesi, Judit K; Crew, Mark D; Portilla, Didier

    2009-11-01

    Our previous studies suggest that peroxisome proliferator-activated receptor-alpha (PPARalpha) plays a critical role in regulating fatty acid beta-oxidation in kidney tissue and this directly correlated with preservation of kidney morphology and function during acute kidney injury. To further study this, we generated transgenic mice expressing PPARalpha in the proximal tubule under the control of the promoter of KAP2 (kidney androgen-regulated protein 2). Segment-specific upregulation of PPARalpha expression by testosterone treatment of female transgenic mice improved kidney function during cisplatin or ischemia-reperfusion-induced acute kidney injury. Ischemia-reperfusion injury or treatment with cisplatin in wild-type mice caused inhibition of fatty-acid oxidation, reduction of mitochondrial genes of oxidative phosphorylation, mitochondrial DNA, fatty-acid metabolism, and the tricarboxylic acid cycle. Similar injury in testosterone-treated transgenic mice resulted in amelioration of these effects. Similarly, there were increases in the levels of 4-hydroxy-2-hexenal-derived lipid peroxidation products in wild-type mice, which were also reduced in the transgenic mice. Similarly, necrosis of the S3 segment was reduced in the two injury models in transgenic mice compared to wild type. Our results suggest proximal tubule PPARalpha activity serves as a metabolic sensor. Its increased expression without the use of an exogenous PPARalpha ligand in the transgenic mice is sufficient to protect kidney function and morphology, and to prevent abnormalities in lipid metabolism associated with acute kidney injury.

  8. Clinical Use of the Urine Biomarker [TIMP-2] × [IGFBP7] for Acute Kidney Injury Risk Assessment.

    PubMed

    Vijayan, Anitha; Faubel, Sarah; Askenazi, David J; Cerda, Jorge; Fissell, William H; Heung, Michael; Humphreys, Benjamin D; Koyner, Jay L; Liu, Kathleen D; Mour, Girish; Nolin, Thomas D; Bihorac, Azra

    2016-07-01

    Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.

  9. Clinical Use of the Urine Biomarker [TIMP-2] × [IGFBP7] for Acute Kidney Injury Risk Assessment.

    PubMed

    Vijayan, Anitha; Faubel, Sarah; Askenazi, David J; Cerda, Jorge; Fissell, William H; Heung, Michael; Humphreys, Benjamin D; Koyner, Jay L; Liu, Kathleen D; Mour, Girish; Nolin, Thomas D; Bihorac, Azra

    2016-07-01

    Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI. PMID:26948834

  10. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology.

    PubMed

    Palevsky, Paul M; Molitoris, Bruce A; Okusa, Mark D; Levin, Adeera; Waikar, Sushrut S; Wald, Ron; Chertow, Glenn M; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Faubel, Sarah G; Kellum, John A; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A

    2012-05-01

    Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.

  11. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1

    PubMed Central

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  12. Acute Kidney Injury Recognition and Management: A Review of the Literature and Current Evidence.

    PubMed

    Shah, Syed Raza; Tunio, Sameer Altaf; Arshad, Mohammad Hussham; Moazzam, Zorays; Noorani, Komal; Feroze, Anushe Mohsin; Shafquat, Maham; Hussain, Huma Syed; Jeoffrey, Syed Ali Hyder

    2016-01-01

    Acute renal failure is defined as a rapid decrease in the glomerular filtration rate, occurring over a period of hours to days and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. AKI is a catastrophic, life-threatening event in critically ill patients. AKI can be divided into pre-renal injury, intrinsic kidney disease (including vascular insults) and obstructive uropathies. The prognosis of AKI is highly dependent on the underlying cause of the injury. Children who have AKI as a component of multisystem failure have a much higher mortality rate than children with intrinsic renal disease. Treatment of AKI is subjected to risk stratification and ongoing damage control measures, such as patients with sepsis, exposure to nephrotoxic agents, ischemia, bloody diarrhea, or volume loss, could be helped by optimizing the fluid administrations, antibiotics possessing least nephrotoxic potential, blood transfusion where hemoglobin is dangerously low, limiting the use of nephrotoxic agents including radio contrast use, while maximize the nutrition. Acute kidney injury remains a complex disorder with an apparent differentiation in pathology between septic and nonseptic forms of the disease. Although more studies are still required, progress in this area has been steady over the last decade with purposeful international collaboration. PMID:26652074

  13. Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

    PubMed Central

    Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

    2015-01-01

    Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

  14. Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models.

    PubMed

    Cui, Jing; Bai, Xue-Yuan; Sun, Xuefeng; Cai, Guangyan; Hong, Quan; Ding, Rui; Chen, Xiangmei

    2015-01-01

    Gentamicin may cause acute kidney injury. The pathogenesis of gentamicin nephrotoxicity is unclear. Autophagy is a highly conserved physiological process involved in removing damaged or aged biological macromolecules and organelles from the cytoplasm. The role of autophagy in the pathogenesis of gentamicin nephrotoxicity is unclear. The miniature pigs are more similar to humans than are those of rodents, and thus they are more suitable as human disease models. Here we established the first gentamicin nephrotoxicity model in miniature pigs, investigated the role of autophagy in gentamicin-induced acute kidney injury, and determined the prevention potential of rapamycin against gentamicin-induced oxidative stress and renal dysfunction. At 0, 1, 3, 5, 7 and 10 days after gentamicin administration, changes in autophagy, oxidative damage, apoptosis and inflammation were assessed in the model group. Compared to the 0-day group, gentamicin administration caused marked nephrotoxicity in the 10-day group. In the kidneys of the 10-day group, the level of autophagy decreased, and oxidative damage and apoptosis were aggravated. After rapamycin intervention, autophagy activity was activated, renal damage in proximal tubules was markedly alleviated, and interstitium infiltration of inflammatory cells was decreased. These results suggest that rapamycin may ameliorate gentamicin-induced nephrotoxicity by enhancing autophagy. PMID:26052900

  15. Etiology and outcomes of anuria in acute kidney injury: a single center study

    PubMed Central

    Choi, Hye Min; Kim, Sun Chul; Kim, Myung-Gyu; Jo, Sang-Kyung; Cho, Won Yong; Kim, Hyoung Kyu

    2014-01-01

    Background It was previously known that anuric acute kidney injury (AKI) is uncommon and its occurrence suggests complete ureteral obstruction, shock, or a major vascular event. As the epidemiology of AKI has significantly changed over the past decade, it is possible that the incidence, etiology, or clinical characteristics of anuric AKI have also changed. Methods A prospective cohort study was conducted that included all patients undergoing renal replacement therapy (RRT) for AKI during a 2-year period in a tertiary hospital. Patients were classified as having anuric, oliguric, or nonoliguric AKI based on their volume of urine when RRT started using the modified Acute Kidney Injury Network criteria. Results Of the 203 patients included in the study, 21.2% met the criteria for anuric AKI. Septic and postoperative AKI were the main causes of anuric AKI, with 60.5% of incidences occurring in hospital. Anuric AKI was associated with a younger age, a lower prevalence of pre-morbid chronic kidney disease and diabetes, more frequent continuous RRT requirement, and multi-organ dysfunction. In addition, patients with anuric AKI had a higher rate of in-hospital mortality and long-term dependence on RRT than patients with nonanuric AKI. Conclusion Anuric AKI is common, with sepsis as the main etiological insult, and is associated with adverse outcomes among patients with AKI who require RRT. PMID:26484014

  16. Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat.

    PubMed

    Cobrin, A R; Blois, S L; Kruth, S A; Abrams-Ogg, A C G; Dewey, C

    2013-12-01

    In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine-specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders. PMID:24152019

  17. Protective actions of administered mesenchymal stem cells in acute kidney injury: relevance to clinical trials.

    PubMed

    Westenfelder, Christof; Togel, Florian E

    2011-09-01

    Current therapies for acute kidney injury remain primarily supportive and have failed to reduce morbidity, mortality (>50%), and associated costs. This prompted our studies in which rats with bilateral ischemia/reperfusion-induced acute kidney injury were treated with bone marrow-derived, culture-expanded allogeneic mesenchymal stem cells. Their administration into the suprarenal aorta after reflow significantly protected renal function and hastened repair, mediated by complex antiapoptotic, mitogenic, anti-inflammatory, and immune modulating actions that were not elicited by isogeneic fibroblasts. Infused mesenchymal stem cells, recruited to renal sites of injury, did not significantly differentiate into target cells but rather disappeared from kidneys and other organs within 72 h. Furthermore, at 3 months, compared with vehicle-treated controls, renal function was well preserved and interstitial fibrosis was absent. These preclinical data served as the scientific basis for a recently completed Phase I Clinical Trial (http://www.clinicaltrials.gov; # NCT00733876), in which patients at high risk for cardiac surgery-associated AKI were treated with allogeneic mesenchymal stem cells. Until now, MSC therapy in the study subjects has been safe, and none of the patients has developed postoperative AKI or subsequent loss of renal function, suggesting that this novel form of therapy may have promise in this group of high-risk patients, which will be further investigated in a Phase II Trial.

  18. Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat.

    PubMed

    Cobrin, A R; Blois, S L; Kruth, S A; Abrams-Ogg, A C G; Dewey, C

    2013-12-01

    In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine-specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders.

  19. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1.

    PubMed

    Bai, Xiao-Zhi; He, Ting; Gao, Jian-Xin; Liu, Yang; Liu, Jia-Qi; Han, Shi-Chao; Li, Yan; Shi, Ji-Hong; Han, Jun-Tao; Tao, Ke; Xie, Song-Tao; Wang, Hong-Tao; Hu, Da-Hai

    2016-01-01

    Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor. The renal function and histological manifestations were determined to evaluate the severity of kidney injury. The levels of acetylated-p53 (Ac-p53), acetylated-p65 (Ac-p65), NF-κB, acetylated-forkhead box O1 (Ac-FoxO1), Bcl-2 and Bax were analyzed to study the underlying mechanisms. Our results suggested that severe burns could induce acute kidney injury, which could be partially reversed by melatonin. Melatonin attenuated oxidative stress, inflammation and apoptosis accompanied by the increased expression of SIRT1. The protective effects of melatonin were abrogated by the inhibition of SIRT1. In conclusion, we demonstrate that melatonin improves severe burn-induced AKI via the activation of SIRT1 signaling. PMID:27599451

  20. Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models

    PubMed Central

    Cui, Jing; Bai, Xue-Yuan; Sun, Xuefeng; Cai, Guangyan; Hong, Quan; Ding, Rui; Chen, Xiangmei

    2015-01-01

    Gentamicin may cause acute kidney injury. The pathogenesis of gentamicin nephrotoxicity is unclear. Autophagy is a highly conserved physiological process involved in removing damaged or aged biological macromolecules and organelles from the cytoplasm. The role of autophagy in the pathogenesis of gentamicin nephrotoxicity is unclear. The miniature pigs are more similar to humans than are those of rodents, and thus they are more suitable as human disease models. Here we established the first gentamicin nephrotoxicity model in miniature pigs, investigated the role of autophagy in gentamicin-induced acute kidney injury, and determined the prevention potential of rapamycin against gentamicin-induced oxidative stress and renal dysfunction. At 0, 1, 3, 5, 7 and 10 days after gentamicin administration, changes in autophagy, oxidative damage, apoptosis and inflammation were assessed in the model group. Compared to the 0-day group, gentamicin administration caused marked nephrotoxicity in the 10-day group. In the kidneys of the 10-day group, the level of autophagy decreased, and oxidative damage and apoptosis were aggravated. After rapamycin intervention, autophagy activity was activated, renal damage in proximal tubules was markedly alleviated, and interstitium infiltration of inflammatory cells was decreased. These results suggest that rapamycin may ameliorate gentamicin-induced nephrotoxicity by enhancing autophagy. PMID:26052900

  1. Acute Kidney Injury Recognition and Management: A Review of the Literature and Current Evidence

    PubMed Central

    Shah, Syed Raza; Tunio, Sameer Altaf; Arshad, Mohammad Hussham; Moazzam, Zorays; Noorani, Komal; Feroze, Anushe Mohsin; Shafquat, Maham; Hussain, Huma Syed; Jeoffrey, Syed Ali Hyder

    2016-01-01

    Acute renal failure is defined as a rapid decrease in the glomerular filtration rate, occurring over a period of hours to days and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. AKI is a catastrophic, life-threatening event in critically ill patients. AKI can be divided into pre-renal injury, intrinsic kidney disease (including vascular insults) and obstructive uropathies. The prognosis of AKI is highly dependent on the underlying cause of the injury. Children who have AKI as a component of multisystem failure have a much higher mortality rate than children with intrinsic renal disease. Treatment of AKI is subjected to risk stratification and ongoing damage control measures, such as patients with sepsis, exposure to nephrotoxic agents, ischemia, bloody diarrhea, or volume loss, could be helped by optimizing the fluid administrations, antibiotics possessing least nephrotoxic potential, blood transfusion where hemoglobin is dangerously low, limiting the use of nephrotoxic agents including radio contrast use, while maximize the nutrition. Acute kidney injury remains a complex disorder with an apparent differentiation in pathology between septic and nonseptic forms of the disease. Although more studies are still required, progress in this area has been steady over the last decade with purposeful international collaboration. PMID:26652074

  2. Resveratrol attenuates acute kidney injury by inhibiting death receptor‑mediated apoptotic pathways in a cisplatin‑induced rat model.

    PubMed

    Hao, Qiufa; Xiao, Xiaoyan; Zhen, Junhui; Feng, Jinbo; Song, Chun; Jiang, Bei; Hu, Zhao

    2016-10-01

    Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti‑inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin‑induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor‑α (TNF‑α), caspase‑8 and Bcl‑2 associated protein X apoptosis regulator (Bax), and decreased expression of anti‑apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl‑2). Administration of resveratrol significantly reversed the cisplatin‑induced alteration in these apoptosis‑associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin‑induced acute kidney injury through inactivation of the death receptor‑mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury. PMID:27600998

  3. Resveratrol attenuates acute kidney injury by inhibiting death receptor-mediated apoptotic pathways in a cisplatin-induced rat model

    PubMed Central

    Hao, Qiufa; Xiao, Xiaoyan; Zhen, Junhui; Feng, Jinbo; Song, Chun; Jiang, Bei; Hu, Zhao

    2016-01-01

    Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti-inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin-induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: Control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor-α (TNF-α), caspase-8 and Bcl-2 associated protein X apoptosis regulator (Bax), and decreased expression of anti-apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl-2). Administration of resveratrol significantly reversed the cisplatin-induced alteration in these apoptosis-associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin-induced acute kidney injury through inactivation of the death receptor-mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury. PMID:27600998

  4. HDL Cholesterol Level Is Associated with Contrast Induced Acute Kidney Injury in Chronic Kidney Disease Patients Undergoing PCI

    PubMed Central

    Park, Hoon Suk; Kim, Chan Joon; Hwang, Byung-Hee; Kim, Tae-Hoon; Koh, Yoon Seok; Park, Hun-Jun; Her, Sung-Ho; Jang, Sung Won; Park, Chul-Soo; Lee, Jong Min; Kim, Hee-Yeol; Jeon, Doo Soo; Kim, Pum-Joon; Yoo, Ki-Dong; Chang, Kiyuk; Jin, Dong Chan; Seung, Ki-Bae

    2016-01-01

    Chronic kidney disease (CKD) is a significant risk factor for contrast induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI). This study included 1592 CKD patients extracted from a prospective multicenter, all comer-based registry of patients undergoing PCI. In multivariate logistic analysis for CI-AKI development, a significant linear trend was observed between the quartiles of HDL-C (quartile 1 vs. 2: odds ratio [OR], 0.716; 95% confidence interval [CI], 0.421–1.219; quartile 1 vs. 3: OR, 0.534; 95% CI, 0.301–0.947; quartile 1 vs. 4: OR, 0.173; 95% CI, 0.079–0.377; P for trend < 0.001). HDL-C quartiles were also negatively correlated with the incidence of CI-AKI; 19.0%, 12.1%, 8.7%, and 3.7% for quartile 1(Q1) (<34 mg/dL), Q2 (34–40 mg/dL), Q3 (40–48 mg/dL), and Q4 (>48 mg/dL) respectively (P < 0.001 overall and for the trend). Multivariate Cox regression analysis for the long term mortality, the highest HDL-C quartile was associated with decreased mortality compared with the lowest HDL-C quartile (hazard ratio [HR] 0.516, 95% CI, 0.320–0.832, P = 0.007). Our study suggests more intensive strategies should be considered for preventing CI-AKI in CKD patients with low serum HDL-C level who is planned for PCI. PMID:27775043

  5. Class I HDAC activity is required for renal protection and regeneration after acute kidney injury.

    PubMed

    Tang, Jinhua; Yan, Yanli; Zhao, Ting C; Gong, Rujun; Bayliss, George; Yan, Haidong; Zhuang, Shougang

    2014-08-01

    Activation of histone deacetylases (HDACs) is required for renal epithelial cell proliferation and kidney development. However, their role in renal tubular cell survival and regeneration after acute kidney injury (AKI) remains unclear. In this study, we demonstrated that all class I HDAC isoforms (1, 2, 3, and 8) were expressed in the renal epithelial cells of the mouse kidney. Inhibition of class I HDACs with MS-275, a highly selective inhibitor, resulted in more severe tubular injury in the mouse model of AKI induced by folic acid or rhabdomyolysis, as indicated by worsening renal dysfunction, increased neutrophil gelatinase-associated lipocalin expression, and enhanced apoptosis and caspase-3 activation. Blocking class I HDAC activity also impaired renal regeneration as evidenced by decreased expression of renal Pax-2, vimentin, and proliferating cell nuclear antigen. Injury to the kidney is accompanied by increased phosphorylation of epidermal growth factor receptor (EGFR), signal transducers and activators of transcription 3 (STAT3), and Akt. Inhibition of class I HDACs suppressed EGFR phosphorylation as well as reduced its expression. MS-275 was also effective in inhibiting STAT3 and Akt phosphorylation, but this treatment did not affect their expression levels. Taken together, these data suggest that the class I HDAC activity contributes to renal protection and functional recovery and is required for renal regeneration after AKI. Furthermore, renal EGFR signaling is subject to regulation by this class of HDACs.

  6. From the nephrologist's point of view: diversity of causes and clinical features of acute kidney injury

    PubMed Central

    Bienholz, Anja; Wilde, Benjamin; Kribben, Andreas

    2015-01-01

    Acute kidney injury (AKI) is a clinical syndrome with multiple entities. Although AKI implies renal damage, functional impairment or both, diagnosis is solely based on the functional parameters of serum creatinine and urine output. The latest definition was provided by the Kidney Disease Improving Global Outcomes (KDIGO) working group in 2012. Independent of the underlying disease, and even in the case of full recovery, AKI is associated with an increased morbidity and mortality. Awareness of the patient's individual risk profile and the diversity of causes and clinical features of AKI is pivotal for optimization of prophylaxes, diagnosis and therapy of each form of AKI. A differentiated and individualized approach is required to improve patient mortality, morbidity, long-term kidney function and eventually the quality of life. In this review, we provide an overview of the different clinical settings in which specific forms of AKI may occur and point out possible diagnostic as well as therapeutic approaches. Secifically AKI is discussed in the context of non-kidney organ failure, organ transplantation, sepsis, malignancy and autoimmune disease. PMID:26251707

  7. Proteome Analysis of Renoprotection Mediated by a Novel Cyclic Helix B Peptide in Acute Kidney Injury

    PubMed Central

    Yang, Cheng; Liu, Junjun; Li, Long; Hu, Meiyu; Long, Yaqiu; Liu, Xiaohui; Zhu, Tongyu; Huang, Xiao; Zhao, Shouliang; Liu, Shangfeng; Rong, Ruiming

    2015-01-01

    We developed a novel, erythropoietin-derived, non-erythropoiesis, cyclic helix B peptide (CHBP) that displays potent renoprotection against acute kidney injury (AKI). To determine the mechanism of CHBP-mediated protection, we investigated the proteomic profile of mice treated with CHBP in a kidney ischemia-reperfusion (IR) injury model. The isobaric tags for relative and absolute quantitation (iTRAQ)-labeled samples were analyzed using a QSTAR XL LC/MS system. In total, 38 differentially expressed proteins (DEPs) were shared by all experimental groups, while 3 DEPs were detected specifically in the IR + CHBP group. Eight significant pathways were identified, and oxidative phosphorylation was shown to be the most important pathway in CHBP-mediated renoprotection. The significant DEPs in the oxidative phosphorylation pathway elicited by CHBP are NADH-ubiquinone oxidoreductase Fe-S protein 6 (NDUFS6), alpha-aminoadipic semialdehyde synthase (AASS) and ATP-binding cassette sub-family D member 3 (ABCD3). The DEPs mentioned above were verified by RT-qPCR and immunostaining in mouse kidneys. We tested 6 DEPs in human biopsy samples from kidney transplant recipients. The trend of differential expression was consistent with that in the murine model. In conclusion, this study helps to elucidate the pharmacological mechanisms of CHBP before clinical translation. PMID:26655840

  8. Tubular cross talk in acute kidney injury: a story of sense and sensibility.

    PubMed

    El-Achkar, Tarek M; Dagher, Pierre C

    2015-06-15

    The mammalian kidney is an organ composed of numerous functional units or nephrons. Beyond the filtering glomerulus of each nephron, various tubular segments with distinct populations of epithelial cells sequentially span the kidney from cortex to medulla. The highly organized folding of the tubules results in a spatial distribution that allows intimate contact between various tubular subsegments. This unique arrangement can promote a newly recognized type of horizontal epithelial-to-epithelial cross talk. In this review, we discuss the importance of this tubular cross talk in shaping the response of the kidney to acute injury in a sense and sensibility model. We propose that injury-resistant tubules such as S1 proximal segments and thick ascending limbs (TAL) can act as "sensors" and thus modulate the responsiveness or "sensibility" of the S2-S3 proximal segments to injury. We also discuss new findings that highlight the importance of tubular cross talk in regulating homeostasis and inflammation not only in the kidney, but also systemically.

  9. Contrast-Induced Acute Kidney Injury: Short and Long-term Implications

    PubMed Central

    Weisbord, Steven D.; Palevsky, Paul M.

    2011-01-01

    The intravascular administration of iodine-based contrast media remains a common cause of acute kidney injury and a leading cause of iatrogenic renal disease. Past research has elucidated the principal risk factors for contrast-induced acute kidney injury (CIAKI) and helped to establish the efficacy of various interventions for the prevention of this condition. The importance of preventing CIAKI has been underscored by a growing number of studies demonstrating strong associations of CIAKI with serious, adverse short and long-term outcomes. However, it remains unclear whether these associations are causal. This is important as considerable healthcare resources are used to prevent CIAKI. If CIAKI is a marker, but not a mediator, of serious, adverse downstream outcomes, more judicious and selective utilization of preventive care may be appropriate. Moreover, with an increasing number of studies reporting the under-utilization of coronary angiography in patients with acute coronary syndrome and underlying CKD, presumably due in part out of a fear of CIAKI, a clear understanding of whether this condition directly results in adverse downstream outcomes is essential. Careful inspection of past studies that investigated the association of CIAKI with adverse short and long-term events sheds light on their strengths and weaknesses and provides insight into how future research may be better able to characterize the short and long-term implications of this iatrogenic condition. PMID:21784279

  10. A Rare Case of Polyneuropathy and Monoclonalgammopathy with Recurrent Acute Kidney Injury

    PubMed Central

    Kim, Eun Jung; Shin, Dong Ho; Jeon, Hee Jung; Rhee, So Yon; Nam, Eun Sook; Park, Ji Young

    2016-01-01

    POEMS syndrome is a rare paraneoplastic syndrome and there are few reports of polyneuropathy and monoclonal gammopathy associated with kidney dysfunction. Here, we report a case of POEMS syndrome with recurrent acute kidney injury (AKI). A 52-year-old man presented with bilateral aggravating paresthesia and latermotor weakness of the lower extremities accompanied by repeated elevation of serum creatinine. The patient was finally diagnosed with POEMS syndrome on the basis of fulfilling the two mandatory major criteria (polyneuropathy and monoclonal gammopathy), one other major criterion (sclerotic bone lesion), and several minor criteria. A renal biopsy was performed to clarify the cause of AKI and showed membranoproliferative glomerulonephritis-like lesions with mesangiolysis and endothelial cell injury. This case illustrates that renal manifestations, not included in the diagnostic criteria for POEMS, can be apparent before various other systemic symptoms. PMID:27453713

  11. Hypercalcemia, Anemia, and Acute Kidney Injury: A Rare Presentation of Sarcoidosis

    PubMed Central

    Sharma, Neeraj; Tariq, Hassan; Uday, Kalpana; Skaradinskiy, Yevgeniy; Niazi, Masooma; Chilimuri, Sridhar

    2015-01-01

    We discuss a case of a 61-year-old woman who presented with substernal chest pain. She was found to have elevated calcium levels, anemia, and acute kidney injury. The hypercalcemia persisted despite therapy with fluids and bisphosphonates. She was found to have nonparathyroid hormone (PTH) mediated hypercalcemia. The chest X-ray did not reveal any pathology. Our Initial impression was likely underlying hematologic malignancy such as lymphoma or multiple myeloma. A bone marrow biopsy was performed that revealed nonnecrotizing granulomatous inflammation. Further workup revealed elevated vitamin 1,25 dihydroxy level, beta-two microglobulin level, and ACE levels. Noncontrast computed tomography (CT) scan of chest showed bilateral apical bronchiectasis, but did not show any lymphadenopathy or evidence of malignancy. Subsequently, a fiber optic bronchoscopy with transbronchial biopsy showed nonnecrotizing granulomatous inflammation consistent with sarcoidosis. After initiating glucocorticoid therapy, the patient's hypercalcemia improved and her kidney function returned to baseline. PMID:26199627

  12. Kidney Tests

    MedlinePlus

    ... taking out waste products and making urine. Kidney tests check to see how well your kidneys are working. They include blood, urine, and imaging tests. Early kidney disease usually does not have signs ...

  13. Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation.

    PubMed

    Golshayan, Déla; Wójtowicz, Agnieszka; Bibert, Stéphanie; Pyndiah, Nitisha; Manuel, Oriol; Binet, Isabelle; Buhler, Leo H; Huynh-Do, Uyen; Mueller, Thomas; Steiger, Jürg; Pascual, Manuel; Meylan, Pascal; Bochud, Pierre-Yves

    2016-04-01

    There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibody-mediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression.

  14. Adenovirus-Mediated Over-Expression of Nrf2 Within Mesenchymal Stem Cells (MSCs) Protected Rats Against Acute Kidney Injury

    PubMed Central

    Mohammadzadeh-Vardin, Mohammad; Habibi Roudkenar, Mehryar; Jahanian-Najafabadi, Ali

    2015-01-01

    Purpose: Recent developments in the field of cell therapy have led to a renewed interest in treatment of acute kidney injury (AKI). However, the early death of transplanted mesenchymal stem cells (MSCs) in stressful microenvironment of a recipient tissue is a major problem with this kind of treatment. The objective of this study was to determine whether overexpression of a cytoprotective factor, nuclear factor erythroid-2 related factor 2 (Nrf2), in MSCs could protect rats against AKI. Methods: The Nrf2 was overexpressed in MSCs by recombinant adenoviruses, and the MSCs were implanted to rats suffering from cisplatin-induced AKI. Results: The obtained results showed that transplantation with the engineered MSCs ameliorates cisplatin-induced AKI. Morphologic features of the investigated kidneys showed that transplantation with the MSCs in which Nrf2 had been overexpressed significantly improved the complications of AKI. Conclusion: These findings suggested that the engineered MSCs might be a good candidate to be further evaluated in clinical trials. However, detailed studies must be performed to investigate the possible carcinogenic effect of Nrf2 overexpression. PMID:26236658

  15. Dengue-induced Acute Kidney Injury (DAKI): A Neglected and Fatal Complication of Dengue Viral Infection--A Systematic Review.

    PubMed

    Mallhi, Tauqeer Hussain; Sarriff, Azmi; Adnan, Azreen Syazril; Khan, Yusra Habib; Hamzah, Azhar Amir; Jummaat, Fauziah; Khan, Amer Hayat

    2015-11-01

    Dengue Viral Infection (DVI) imperils an estimated 2.5 billion people living in tropical and subtropical regions. World Health Organization (2011) guidelines also classified dengue as 'Expanded Dengue Syndrome' to incorporate wide spectrum of unusual manifestations of dengue infection affecting various organ systems - including liver, kidney, heart and brain. Renal involvements are least appreciated area of dengue infection, therefore, we systematically reviewed studies describing renal disorders in dengue infection, with emphasis on Acute Kidney Injury (AKI). The purpose of current review is to underscore clinicians’attention to this neglected intricacy of DVI. It suggests that dengue induced renal involvements vary from glomerulonephritis, nephrotic range proteinuria and AKI. We observed great disparity in incidence of AKI among dengue patients, based upon criteria used to define AKI. AKI among dengue patients was found to be associated with significant morbidity, mortality and longer hospitalization, adding financial burden to patients and healthcare system. Additionally, we identified several predictors of AKI in dengue patients including old age, obesity, severe dengue infection and concurrent bacterial or viral infection. Direct viral injury and deposition of antigen-antibody complex in glomerulus were found to be possible causes of renal disorders in dengue infection. Prior knowledge of clinico-laboratory characteristics and risk factors with early detection of AKI by using appropriate criteria would not only reduce morbidity and mortality but also decrease burden to patients and healthcare system. PMID:26577971

  16. Age of red blood cells and outcome in acute kidney injury

    PubMed Central

    2013-01-01

    Introduction Transfusion of red blood cells (RBCs) and, in particular, older RBCs has been associated with increased short-term mortality in critically ill patients. We evaluated the association between age of transfused RBCs and acute kidney injury (AKI), hospital, and 90-day mortality in critically ill patients. Methods We conducted a prospective, observational, predefined sub-study within the FINNish Acute Kidney Injury (FINNAKI) study. This study included all elective ICU admissions with expected ICU stay of more than 24 hours and all emergency admissions from September to November 2011. To study the age of RBCs, we classified transfused patients into quartiles according to the age of oldest transfused RBC unit in the ICU. AKI was defined according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Results Out of 1798 patients, 652 received at least one RBC unit. The median [interquartile range] age of the oldest RBC unit transfused was 12 [11-13] days in the freshest quartile and 21 [17-27] days in the quartiles 2 to 4. On logistic regression, RBC age was not associated with the development of KDIGO stage 3 AKI. Patients in the quartile of freshest RBCs had lower crude hospital and 90-day mortality rates compared to those in the quartiles of older blood. After adjustments, older RBC age was associated with significantly increased risk for hospital mortality. Age, Simplified Acute Physiology Score II (SAPS II)-score without age points, maximum Sequental Organ Failure Assessment (SOFA) score and the total number of transfused RBC units were independently associated with 90-day mortality. Conclusions The age of transfused RBC units was independently associated with hospital mortality but not with 90-day mortality or KDIGO stage 3 AKI. The number of transfused RBC units was an independent risk factor for 90-day mortality. PMID:24093554

  17. The effect of pravastatin on acute rejection after kidney transplantation--a pilot study.

    PubMed

    Katznelson, S; Wilkinson, A H; Kobashigawa, J A; Wang, X M; Chia, D; Ozawa, M; Zhong, H P; Hirata, M; Cohen, A H; Teraski, P I

    1996-05-27

    Hyperlipidemia is an important complication of kidney transplantation affecting up to 74% of recipients. HMG-CoA reductase inhibitors are reported to provide safe and effective treatment for this problem. A recent study suggests that pravastatin, an HMG-CoA reductase inhibitor, also decreases the incidence of both clinically severe acute rejection episodes and natural killer cell cytotoxicity after orthotopic heart transplantation. We have performed a prospective randomized pilot study of the effect of pravastatin on these same parameters after cadaveric kidney transplantation. Graft recipients were randomized to receive pravastatin after transplantation or no pravastatin (24 patients in each group) in addition to routine cyclosporine and prednisone immunosuppression. Lipid levels, acute rejection episodes and serial natural killer cell cytotoxicities were followed for 4 months after the transplant. At the end of the study period, pravastatin had successfully controlled mean total cholesterol levels (202.6 +/- 9.3 vs. 236.5 +/- 11.9 mg/dl, P < 0.02), LDL levels (107.9 +/- 6.6 vs.149.6 +/- 10.7 mg/dl, P < 0.002), and triglyceride levels (118.8 +/- 14.2 vs. 157.2 +/- 13.8 mg/dl, P < 0.05). In addition, the pravastatin-treated group experienced a reduction in the incidence of biopsy-proven acute rejection episodes (25% vs. 58%, P = 0.01), the incidence of multiple rejections episodes (P < 0.05), and the use of both pulse methylprednisolone (P = 0.01) and OKT3 (P = 0.02). Mean natural killer cell cytotoxicity was similarly reduced (11.3 +/- 1.6 vs. 20.0 +/- 2.0% lysis of K562 target cells, P < 0.002). These data suggest that pravastatin exerts an additional immunosuppressive effect in kidney transplant recipients treated with cyclosporine-based immunosuppression. PMID:8633373

  18. Dynamic MRI-based computer aided diagnostic systems for early detection of kidney transplant rejection: A survey

    NASA Astrophysics Data System (ADS)

    Mostapha, Mahmoud; Khalifa, Fahmi; Alansary, Amir; Soliman, Ahmed; Gimel'farb, Georgy; El-Baz, Ayman

    2013-10-01

    Early detection of renal transplant rejection is important to implement appropriate medical and immune therapy in patients with transplanted kidneys. In literature, a large number of computer-aided diagnostic (CAD) systems using different image modalities, such as ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), and radionuclide imaging, have been proposed for early detection of kidney diseases. A typical CAD system for kidney diagnosis consists of a set of processing steps including: motion correction, segmentation of the kidney and/or its internal structures (e.g., cortex, medulla), construction of agent kinetic curves, functional parameter estimation, diagnosis, and assessment of the kidney status. In this paper, we survey the current state-of-the-art CAD systems that have been developed for kidney disease diagnosis using dynamic MRI. In addition, the paper addresses several challenges that researchers face in developing efficient, fast and reliable CAD systems for the early detection of kidney diseases.

  19. Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions

    PubMed Central

    Pabla, Navjotsingh; Gibson, Alice A.; Buege, Mike; Ong, Su Sien; Li, Lie; Hu, Shuiying; Du, Guoqing; Sprowl, Jason A.; Vasilyeva, Aksana; Janke, Laura J.; Schlatter, Eberhard; Chen, Taosheng; Ciarimboli, Giuliano; Sparreboom, Alex

    2015-01-01

    Acute kidney injury (AKI) is a potentially fatal syndrome characterized by a rapid decline in kidney function caused by ischemic or toxic injury to renal tubular cells. The widely used chemotherapy drug cisplatin accumulates preferentially in the renal tubular cells and is a frequent cause of drug-induced AKI. During the development of AKI the quiescent tubular cells reenter the cell cycle. Strategies that block cell-cycle progression ameliorate kidney injury, possibly by averting cell division in the presence of extensive DNA damage. However, the early signaling events that lead to cell-cycle activation during AKI are not known. In the current study, using mouse models of cisplatin nephrotoxicity, we show that the G1/S-regulating cyclin-dependent kinase 4/6 (CDK4/6) pathway is activated in parallel with renal cell-cycle entry but before the development of AKI. Targeted inhibition of CDK4/6 pathway by small-molecule inhibitors palbociclib (PD-0332991) and ribociclib (LEE011) resulted in inhibition of cell-cycle progression, amelioration of kidney injury, and improved overall survival. Of additional significance, these compounds were found to be potent inhibitors of organic cation transporter 2 (OCT2), which contributes to the cellular accumulation of cisplatin and subsequent kidney injury. The unique cell-cycle and OCT2-targeting activities of palbociclib and LEE011, combined with their potential for clinical translation, support their further exploration as therapeutic candidates for prevention of AKI. PMID:25848011

  20. Acute kidney injury on admission to the intensive care unit: where to go from here?

    PubMed

    Ostermann, Marlies

    2008-01-01

    Acute kidney injury (AKI) is a common problem, especially in critically ill patients. In Critical Care, Kolhe and colleagues report that 6.3% of 276,731 patients in 170 intensive care units (ICUs) in the UK had evidence of severe AKI within the first 24 hours of admission to ICU. ICU and hospital mortality as well as length of stay in hospital were significantly increased. In light of this serious burden on individuals and the health system in general, the following commentary discusses the current state of knowledge of AKI in ICU and calls for more attention to preventive strategies.

  1. Radiographic Contrast-Media-Induced Acute Kidney Injury: Pathophysiology and Prophylactic Strategies

    PubMed Central

    2013-01-01

    Contrast-induced acute kidney injury (CI-AKI) is one of the most widely discussed and debated topics in cardiovascular medicine. With increasing number of contrast-media- (CM-) enhanced imaging studies being performed and growing octogenarian population with significant comorbidities, incidence of CI-AKI remains high. In this review, pathophysiology of CI-AKI, its relationship with different types of CM, role of serum and urinary biomarkers for diagnosing CI-AKI, and various prophylactic strategies used for nephroprotection against CI-AKI are discussed in detail. PMID:24967281

  2. A GAP in our knowledge of vascular signaling in acute kidney injury.

    PubMed

    Basile, David P

    2011-08-01

    Injury resulting from ischemia-reperfusion injury is a multifactorial process involving compromised function in both the tubular and the vascular compartments. Multiple vasoactive compounds have been implicated in the profound vasoconstriction that occurs in response to ischemia-reperfusion injury, and many of these factors signal through common G protein-coupled receptors. The report by Siedlecki et al. highlights the important roles of RGS4, a GTPase-accelerating protein (GAP), in the regulation of vascular tone in the setting of acute kidney injury.

  3. “Knot Stent”: An Unusual Cause of Acute Renal Failure in Solitary Kidney

    PubMed Central

    Moufid, Kamal; Touiti, Driss; Mohamed, Lezrek

    2012-01-01

    The insertion of indwelling ureteric stents is a routine procedure in urology practice. Complications secondary to the insertion of these stents have also increased, such as stent encrustation, stent fragmentation, stone formation, and recurrent urinary tract infections. Knot formation within the renal pelvis or in the coiled portion of the ureteral stent is an extremely rare condition, with less than 15 cases reported in literature. The authors report a rare case of knotted stent, complicated by an obstructive acute renal failure and urosepsis, in a patient with a solitary functioning kidney. PMID:22919550

  4. Acute kidney injury: new concepts in definition, diagnosis, pathophysiology, and treatment.

    PubMed

    Lattanzio, Michael R; Kopyt, Nelson P

    2009-01-01

    Acute kidney injury (AKI) is increasingly recognized in all fields of medical practice. Unfortunately, this syndrome has been plagued by inconsistent definitions, simplistic pathophysiologic schemas, and insensitive diagnostic tools. Recent advances in defining AKI, understanding its pathophysiology, and improving the diagnostic accuracy of the testing tools available eventually will impact disease management and clinical outcomes. Prompt recognition and treatment of AKI remain the cornerstone of clinical management for this high-mortality, high-cost syndrome. The authors provide the most recent updates in the definition, diagnosis, pathophysiology, and treatment options for patients with AKI, providing a stepwise approach to clinical evaluation for use in all fields of medical practice.

  5. AKI and Genetics: Evolving Concepts in the Genetics of Acute Kidney Injury: Implications for Pediatric AKI.

    PubMed

    Lee-Son, Kathy; Jetton, Jennifer G

    2016-03-01

    In spite of recent advances in the field of acute kidney injury (AKI) research, morbidity and mortality remain high for AKI sufferers. The study of genetic influences in AKI pathways is an evolving field with potential for improving outcomes through the identification of risk and protective factors at the individual level that may in turn allow for the development of rational therapeutic interventions. Studies of single nucleotide polymorphisms, individual susceptibility to nephrotoxic medications, and epigenetic factors comprise a growing body of research in this area. While promising, this field is still only emerging, with a small number of studies in humans and very little data in pediatric patients. PMID:27617143

  6. Acute kidney injury: risk factors and management challenges in developing countries.

    PubMed

    Ponce, Daniela; Balbi, Andre

    2016-01-01

    Acute kidney injury (AKI) is a major global health problem in both developed and developing nations, negatively affecting patient morbidity and responsible for an estimated 1.4 million deaths per year. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in developing countries presents major challenges not only because of the lack of resources but also because of the scarce data addressing the epidemiology and causes of AKI in developing countries, the limited health care resources to diagnose and treat AKI, and the poor awareness of the impact of AKI on patient outcomes. PMID:27578995

  7. Successful recovery from an acute kidney injury due to amniotic fluid embolism.

    PubMed

    Ihara, Katsuhito; Naito, Shotaro; Okado, Tomokazu; Rai, Tatemitu; Mori, Yutaro; Toda, Takayuki; Uchida, Shinichi; Sasaki, Sei; Matsui, Noriaki

    2015-01-01

    A 33-year-old Japanese woman at 40 weeks gestation visited the maternity hospital after imminent labor had begun. After the delivery, persistent bleeding developed resulting in hemorrhagic shock. Although the hemorrhage was eventually controlled, hepatic and renal dysfunction occurred, leading to acute kidney injury (AKI). The patient's clinical presentation was suggestive of amniotic fluid embolism (AFE). We subsequently initiated continuous renal replacement therapy (RRT) for AKI. The patient's condition improved, she discontinued RRT, and her renal function recovered. We herein report a patient who successfully recovered from AKI caused by AFE. PMID:25742893

  8. Acute kidney injury: risk factors and management challenges in developing countries

    PubMed Central

    Ponce, Daniela; Balbi, Andre

    2016-01-01

    Acute kidney injury (AKI) is a major global health problem in both developed and developing nations, negatively affecting patient morbidity and responsible for an estimated 1.4 million deaths per year. Although the International Society of Nephrology set a goal of eliminating preventable deaths from AKI by 2025, implementation of this program in developing countries presents major challenges not only because of the lack of resources but also because of the scarce data addressing the epidemiology and causes of AKI in developing countries, the limited health care resources to diagnose and treat AKI, and the poor awareness of the impact of AKI on patient outcomes. PMID:27578995

  9. Renal blood flow and acute kidney injury in septic shock: an arduous conflict that smolders intrarenally?

    PubMed

    Honore, Patrick M; Jacobs, Rita; De Waele, Elisabeth; Diltoer, Marc; Spapen, Herbert D

    2016-07-01

    Sepsis-induced acute kidney injury (SAKI) is traditionally viewed as a process driven by a reduced blood flow and prone to benefit from vasopressive support. In ovine hyperdynamic septic shock, Lankadeva et al. report a significant and flow-independent intrarenal perfusion and oxygenation "mismatch" jeopardizing the renal medulla that was aggravated by norepinephrine. Medullary and urinary oxygenation changed in parallel, suggesting that urinary oxygenation may act as a biomarker to predict SAKI. PMID:27312443

  10. Methemoglobinemia due to quinine causing severe acute kidney injury in a child

    PubMed Central

    Kudale, S.; Sethi, S. K.; Dhaliwal, M.; Kher, V.

    2014-01-01

    Congenital methemoglobinemia is a rare condition resulting from a deficiency of nicotinamide adenine dinucleotide-cytochrome b5 reductase. Acquired methemoglobinemia may result due to certain drugs, chemicals and food items. Information on epidemiological determinants from India is sparse. This report describes methemoglobinemia in a 4-year-old child after parenteral administration of quinine causing acute kidney injury. This case emphasizes the need of awareness of potential adverse events of antimalarial drugs. Prompt management of methemoglobinemia is essential to avoid potential life-threatening complications. PMID:25484537

  11. CDK4/6 inhibition induces epithelial cell cycle arrest and ameliorates acute kidney injury

    PubMed Central

    DiRocco, Derek P.; Bisi, John; Roberts, Patrick; Strum, Jay; Wong, Kwok-Kin; Sharpless, Norman

    2013-01-01

    Acute kidney injury (AKI) is common and urgently requires new preventative therapies. Expression of a cyclin-dependent kinase (CDK) inhibitor transgene protects against AKI, suggesting that manipulating the tubular epithelial cell cycle may be a viable therapeutic strategy. Broad spectrum small molecule CDK inhibitors are protective in some kidney injury models, but these have toxicities and epithelial proliferation is eventually required for renal repair. Here, we tested a well-tolerated, novel and specific small molecule inhibitor of CDK4 and CDK6, PD 0332991, to investigate the effects of transient cell cycle inhibition on epithelial survival in vitro and kidney injury in vivo. We report that CDK4/6 inhibition induced G0/G1 cycle arrest in cultured human renal proximal tubule cells (hRPTC) at baseline and after injury. Induction of transient G0/G1 cycle arrest through CDK4/6 inhibition protected hRPTC from DNA damage and caspase 3/7 activation following exposure to the nephrotoxins cisplatin, etoposide, and antimycin A. In vivo, mice treated with PD 0332991 before ischemia-reperfusion injury (IRI) exhibited dramatically reduced epithelial progression through S phase 24 h after IRI. Despite reduced epithelial proliferation, PD 0332991 ameliorated kidney injury as reflected by improved serum creatinine and blood urea nitrogen levels 24 h after injury. Inflammatory markers and macrophage infiltration were significantly decreased in injured kidneys 3 days following IRI. These results indicate that induction of proximal tubule cell cycle arrest with specific CDK4/6 inhibitors, or “pharmacological quiescence,” represents a novel strategy to prevent AKI. PMID:24338822

  12. Role of TRPV1 Channels in Ischemia/Reperfusion-Induced Acute Kidney Injury

    PubMed Central

    Chen, Lan; Markó, Lajos; Kaßmann, Mario; Zhu, Ye; Wu, Kaiyin; Gollasch, Maik

    2014-01-01

    Objectives Transient receptor potential vanilloid 1 (TRPV1) -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist) and using Trpv1−/− mice. Methods and Results Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight) or capsazepine (50 mg/kg body weight). Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL) abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE) or epoxyeicosatrienoic acids (EETs) are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. Conclusions Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli. PMID:25330307

  13. CDK4/6 inhibition induces epithelial cell cycle arrest and ameliorates acute kidney injury.

    PubMed

    DiRocco, Derek P; Bisi, John; Roberts, Patrick; Strum, Jay; Wong, Kwok-Kin; Sharpless, Norman; Humphreys, Benjamin D

    2014-02-15

    Acute kidney injury (AKI) is common and urgently requires new preventative therapies. Expression of a cyclin-dependent kinase (CDK) inhibitor transgene protects against AKI, suggesting that manipulating the tubular epithelial cell cycle may be a viable therapeutic strategy. Broad spectrum small molecule CDK inhibitors are protective in some kidney injury models, but these have toxicities and epithelial proliferation is eventually required for renal repair. Here, we tested a well-tolerated, novel and specific small molecule inhibitor of CDK4 and CDK6, PD 0332991, to investigate the effects of transient cell cycle inhibition on epithelial survival in vitro and kidney injury in vivo. We report that CDK4/6 inhibition induced G0/G1 cycle arrest in cultured human renal proximal tubule cells (hRPTC) at baseline and after injury. Induction of transient G0/G1 cycle arrest through CDK4/6 inhibition protected hRPTC from DNA damage and caspase 3/7 activation following exposure to the nephrotoxins cisplatin, etoposide, and antimycin A. In vivo, mice treated with PD 0332991 before ischemia-reperfusion injury (IRI) exhibited dramatically reduced epithelial progression through S phase 24 h after IRI. Despite reduced epithelial proliferation, PD 0332991 ameliorated kidney injury as reflected by improved serum creatinine and blood urea nitrogen levels 24 h after injury. Inflammatory markers and macrophage infiltration were significantly decreased in injured kidneys 3 days following IRI. These results indicate that induction of proximal tubule cell cycle arrest with specific CDK4/6 inhibitors, or "pharmacological quiescence," represents a novel strategy to prevent AKI.

  14. “SHOUT” to improve the quality of care delivered to patients with acute kidney injury at Great Western Hospital

    PubMed Central

    Brady, Paul; Gorham, James; Kosti, Angeliki; Seligman, William; Courtney, Alona; Mazan, Karolina; Paterson, Stuart; Ramcharitar, Steve; Chandrasekaran, Badri; Juniper, Mark; Greamspet, Mala; Daniel, Jessica; Chalstrey, Sue; Ahmed, Ijaz; Dasgupta, Tanaji

    2015-01-01

    Acute kidney injury (AKI) affects up to 20% of all patients admitted to hospital, and is associated with a higher risk of adverse clinical outcomes, increased healthcare costs, as well as long term risks of chronic kidney disease and end stage renal failure. The aim of this project was to improve the quality of care for patients with AKI admitted to the acute medical unit (AMU) at the Great Western Hospital (GWH). We assessed awareness and self reported confidence among physicians in our Trust, in addition to basic aspects of care relevant to AKI on our AMU. A multifaceted quality improvement strategy was developed, which included measures to improve awareness such as a Trust wide AKI awareness day, and reconfiguring the admission proforma on our AMU in order to enhance risk assessment, staging, and early response to AKI. Ancillary measures such as the dissemination of flashcards for lanyards containing core information were also used. Follow up assessments showed that foundation year one (FY1) doctors’ self reported confidence in managing AKI increased from 2.8 to 4.2, as measured on a five point Likert scale (P=0.0003). AKI risk assessment increased from 13% to 57% (P=0.07) following a change in the admission proforma. Documentation of the diagnosis of AKI increased from 66% to 95% (P=0.038) among flagged patients. Documentation of urine dip results increased from 33% to 73% (P=0.01), in addition to a rise in appropriate referral for specialist input, although this was not statistically significant. Our results suggest that using the twin approaches of improving awareness, and small changes to systemic factors such as modification of the admission proforma, can lead to significant enhancements in the quality of care of patients with AKI. PMID:26734401

  15. "SHOUT" to improve the quality of care delivered to patients with acute kidney injury at Great Western Hospital.

    PubMed

    Brady, Paul; Gorham, James; Kosti, Angeliki; Seligman, William; Courtney, Alona; Mazan, Karolina; Paterson, Stuart; Ramcharitar, Steve; Chandrasekaran, Badri; Juniper, Mark; Greamspet, Mala; Daniel, Jessica; Chalstrey, Sue; Ahmed, Ijaz; Dasgupta, Tanaji

    2015-01-01

    Acute kidney injury (AKI) affects up to 20% of all patients admitted to hospital, and is associated with a higher risk of adverse clinical outcomes, increased healthcare costs, as well as long term risks of chronic kidney disease and end stage renal failure. The aim of this project was to improve the quality of care for patients with AKI admitted to the acute medical unit (AMU) at the Great Western Hospital (GWH). We assessed awareness and self reported confidence among physicians in our Trust, in addition to basic aspects of care relevant to AKI on our AMU. A multifaceted quality improvement strategy was developed, which included measures to improve awareness such as a Trust wide AKI awareness day, and reconfiguring the admission proforma on our AMU in order to enhance risk assessment, staging, and early response to AKI. Ancillary measures such as the dissemination of flashcards for lanyards containing core information were also used. Follow up assessments showed that foundation year one (FY1) doctors' self reported confidence in managing AKI increased from 2.8 to 4.2, as measured on a five point Likert scale (P=0.0003). AKI risk assessment increased from 13% to 57% (P=0.07) following a change in the admission proforma. Documentation of the diagnosis of AKI increased from 66% to 95% (P=0.038) among flagged patients. Documentation of urine dip results increased from 33% to 73% (P=0.01), in addition to a rise in appropriate referral for specialist input, although this was not statistically significant. Our results suggest that using the twin approaches of improving awareness, and small changes to systemic factors such as modification of the admission proforma, can lead to significant enhancements in the quality of care of patients with AKI.

  16. Coexistence of Acute Crescent Glomerulonephritis and IgG4-Related Kidney Disease

    PubMed Central

    Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng

    2016-01-01

    Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450

  17. Acute kidney injury associated with androgenic steroids and nutritional supplements in bodybuilders†

    PubMed Central

    Almukhtar, Safa E.; Abbas, Alaa A.; Muhealdeen, Dana N.; Hughson, Michael D.

    2015-01-01

    Four bodybuilders who injected anabolic steroids and ingested commercial protein (78–104 g/day) and creatine (15 g/day) products presented with serum creatinine levels between 229.84 and 335.92 µmol/L (2.6–3.8 mg/dL). Renal biopsies revealed acute tubular necrosis. Four weeks after discontinuing injections and supplements, serum creatinine was in the normal range and estimated glomerular filtration rate > 1.00 mL/s (60 mL/min), including two patients with biopsies showing >30% interstitial fibrosis and tubular atrophy. The findings highlight a risk for acute and potentially chronic kidney injury among young men abusing anabolic steroids and using excessive amounts of nutritional supplements. PMID:26251708

  18. Acute kidney injury in patients with paraquat intoxication; a case report and review of the literature.

    PubMed

    Safaei Asl, Afshin; Dadashzadeh, Peyman

    2016-01-01

    Paraquat and diquat are classified as bipyridyl compounds not only leads to acute organ damage, but also to a variety of complications. Patients with severe paraquat-induced poisoning may succumb to multiple organ failure involving the circulatory and respiratory systems. Deliberate self-poisoning with paraquat continues to be a major public health concern in many developing countries. At present there is no specific antidote to paraquat poisoning, hence the need to more focus on prevention and in cases of poisoning aggressive decontamination to prevent further absorption. This article presented a 12-year-old male with acute kidney injury following the ingestion of paraquat in suicidal attempt and serves to explore the complications associated with paraquat poisoning and current recommended treatment. PMID:27689124

  19. Acute kidney injury in patients with paraquat intoxication; a case report and review of the literature

    PubMed Central

    Safaei Asl, Afshin; Dadashzadeh, Peyman

    2016-01-01

    Paraquat and diquat are classified as bipyridyl compounds not only leads to acute organ damage, but also to a variety of complications. Patients with severe paraquat-induced poisoning may succumb to multiple organ failure involving the circulatory and respiratory systems. Deliberate self-poisoning with paraquat continues to be a major public health concern in many developing countries. At present there is no specific antidote to paraquat poisoning, hence the need to more focus on prevention and in cases of poisoning aggressive decontamination to prevent further absorption. This article presented a 12-year-old male with acute kidney injury following the ingestion of paraquat in suicidal attempt and serves to explore the complications associated with paraquat poisoning and current recommended treatment PMID:27689124

  20. Acute kidney injury in patients with paraquat intoxication; a case report and review of the literature

    PubMed Central

    Safaei Asl, Afshin; Dadashzadeh, Peyman

    2016-01-01

    Paraquat and diquat are classified as bipyridyl compounds not only leads to acute organ damage, but also to a variety of complications. Patients with severe paraquat-induced poisoning may succumb to multiple organ failure involving the circulatory and respiratory systems. Deliberate self-poisoning with paraquat continues to be a major public health concern in many developing countries. At present there is no specific antidote to paraquat poisoning, hence the need to more focus on prevention and in cases of poisoning aggressive decontamination to prevent further absorption. This article presented a 12-year-old male with acute kidney injury following the ingestion of paraquat in suicidal attempt and serves to explore the complications associated with paraquat poisoning and current recommended treatment

  1. Acute kidney injury associated with androgenic steroids and nutritional supplements in bodybuilders(†).

    PubMed

    Almukhtar, Safa E; Abbas, Alaa A; Muhealdeen, Dana N; Hughson, Michael D

    2015-08-01

    Four bodybuilders who injected anabolic steroids and ingested commercial protein (78-104 g/day) and creatine (15 g/day) products presented with serum creatinine levels between 229.84 and 335.92 µmol/L (2.6-3.8 mg/dL). Renal biopsies revealed acute tubular necrosis. Four weeks after discontinuing injections and supplements, serum creatinine was in the normal range and estimated glomerular filtration rate > 1.00 mL/s (60 mL/min), including two patients with biopsies showing >30% interstitial fibrosis and tubular atrophy. The findings highlight a risk for acute and potentially chronic kidney injury among young men abusing anabolic steroids and using excessive amounts of nutritional supplements. PMID:26251708

  2. The role of neutrophil gelatinase-associated lipocalin in predicting acute kidney injury in patients undergoing off-pump coronary artery bypass graft: A pilot study

    PubMed Central

    Jain, Vishal; Mehta, Yatin; Gupta, Abhinav; Sharma, Reetesh; Raizada, Arun; Trehan, Naresh

    2016-01-01

    Objective: Acute kidney injury (AKI) is a commonly encountered postoperative complication after cardiac surgery especially in high risk patients. AKI though seen more commonly after conventional on pump coronary artery bypass surgery (CCABG), is not uncommon after off pump coronary bypass surgery (OPCAB). Various biomarkers have shown promise over last one decade as an early marker for predicting AKI postoperatively. NGAL is one such biomarker whose concentration is increased in urine after any nephrotoxic and ischemic insult. The objective of this study was to assess the role of urine NGAL in predicting AKI after OPCAB in patients with increased risk of developing AKI. Design: A prospective cohort study. Setting: A clinical study in a multi specialty hospital. Participants: Eighty patients. Materials and Methods: study was approved by the hospital research ethics committee. 80 patients posted for OPCAB with an increased risk of developing AKI defined as having a Cleveland Clinic Foundation Acute renal failure scoring System score of ≥6 were included in the study. Patients with coronary angiography (CAG) within 48 hrs prior to surgery, pre-existing AKI, preoperative renal replacement therapy (RRT) and CKD stage 5 were excluded. Urine NGAL level before the start of surgery baseline and at 4 hrs post surgery were done. Renal function tests were assessed on the day of surgery (4 hrs post surgery) and on the next three days. Result: Seven patients developed AKI as defined by acute kidney infection network (AKIN) and risk injury failure loss end stage (RIFLE) criteria for AKI. NGAL value at 4 hrs in patients who developed AKI was significantly higher than in those patients who did not develop AKI (P < 0.05). Conclusion: urine NGAL is an early biomarker of acute kidney injury in patients undergoing OPCAB surgeries. However, large multicentre studies may be needed to confirm it. PMID:27052061

  3. Topiramate as a rare cause of reversible Fanconi syndrome and acute kidney injury: a case report and literature review.

    PubMed

    Meseeha, Marcelle G; Attia, Maximos N; Kolade, Victor O

    2016-01-01

    Topiramate (TPM) is a sulfa-derivative monosaccharide that has been used for multiple indications in the last several years. We describe a 53-year-old woman with known chronic kidney disease stage 2 and baseline creatinine of 1 mg/dL who developed acute kidney injury and proximal renal tubular dysfunction while on TPM for depression. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between TPM and acute kidney injury as well as proximal tubular dysfunction; these renal conditions resolved on withdrawal of TPM. To our knowledge, this is the first report of such a scenario. Patients receiving TPM therapy should be closely monitored for evidence of kidney dysfunction and electrolyte abnormalities. PMID:26908388

  4. Topiramate as a rare cause of reversible Fanconi syndrome and acute kidney injury: a case report and literature review

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    Topiramate (TPM) is a sulfa-derivative monosaccharide that has been used for multiple indications in the last several years. We describe a 53-year-old woman with known chronic kidney disease stage 2 and baseline creatinine of 1 mg/dL who developed acute kidney injury and proximal renal tubular dysfunction while on TPM for depression. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between TPM and acute kidney injury as well as proximal tubular dysfunction; these renal conditions resolved on withdrawal of TPM. To our knowledge, this is the first report of such a scenario. Patients receiving TPM therapy should be closely monitored for evidence of kidney dysfunction and electrolyte abnormalities. PMID:26908388

  5. Early chronic kidney disease-mineral bone disorder stimulates vascular calcification.

    PubMed

    Fang, Yifu; Ginsberg, Charles; Sugatani, Toshifumi; Monier-Faugere, Marie-Claude; Malluche, Hartmut; Hruska, Keith A

    2014-01-01

    The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an extremely important complication of kidney diseases. Here we tested whether CKD-MBD causes vascular calcification in early kidney failure by developing a mouse model of early CKD in a background of atherosclerosis-stimulated arterial calcification. CKD equivalent in glomerular filtration reduction to human CKD stage 2 stimulated early vascular calcification and inhibited the tissue expression of α-klotho (klotho) in the aorta. In addition, osteoblast transition in the aorta was stimulated by early CKD as shown by the expression of the critical transcription factor Runx2. The ligand associated with the klotho-fibroblast growth factor receptor complex, FGF23, was found to be expressed in the vascular media of sham-operated mice. Its expression was decreased in early CKD. Increased circulating levels of the osteocyte-secreted proteins, FGF23, and sclerostin may have been related to increased circulating klotho levels. Finally, we observed low-turnover bone disease with a reduction in bone formation rates more than bone resorption. Thus, the CKD-MBD, characterized by cardiovascular risk factors, vascular calcification, increased circulating klotho, FGF23 and sclerostin levels, and low-turnover renal osteodystrophy, was established in early CKD. Early CKD caused a reduction of vascular klotho, stimulated vascular osteoblastic transition, increased osteocytic secreted proteins, and inhibited skeletal modeling producing the CKD-MBD. PMID:23884339

  6. Detection of Occult Acute Kidney Injury in Glucose-6-Phosphate Dehydrogenase Deficiency Anemia

    PubMed Central

    Abdel Hakeem, Gehan Lotfy; Abdel Naeem, Emad Allam; Swelam, Salwa Hussein; El Morsi Aboul Fotoh, Laila; El Mazary, Abdel Azeem Mohamed; Abdel Fadil, Ashraf Mohamed; Abdel Hafez, Asmaa Hosny

    2016-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency anemia is associated with intravascular hemolysis. The freely filtered hemoglobin can damage the kidney. We aimed to assess any subclinical renal injury in G6PD children. Methods Sixty children were included. Thirty G6PD deficiency anemia children were enrolled during the acute hemolytic crisis and after the hemolytic episode had elapsed. Another thirty healthy children were included as controls. Serum cystatin C, creatinine levels, and urinary albumin/creatinine (A/C) ratio were measured, and the glomerular filtration rate (GFR) was calculated. Results Significantly higher urinary A/C ratio (p=0.001,0.002 respectively) and lower GFR (p=0.001 for both) were found during hemolysis and after the hemolytic episode compared to the controls. Also, significant higher serum cystatin C (p=0.001), creatinine (p=0.05) and A/C (p= 0.001) ratio and insignificant lower GFR (p=0.3) during acute hemolytic crisis compared to the same children after the hemolytic episode subsided. Conclusions G6PD deficiency anemia is associated with a variable degree of acute renal injury during acute hemolytic episodes which may persist after elapsing of the hemolytic crises. PMID:27648201

  7. Detection of Occult Acute Kidney Injury in Glucose-6-Phosphate Dehydrogenase Deficiency Anemia

    PubMed Central

    Abdel Hakeem, Gehan Lotfy; Abdel Naeem, Emad Allam; Swelam, Salwa Hussein; El Morsi Aboul Fotoh, Laila; El Mazary, Abdel Azeem Mohamed; Abdel Fadil, Ashraf Mohamed; Abdel Hafez, Asmaa Hosny

    2016-01-01

    Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency anemia is associated with intravascular hemolysis. The freely filtered hemoglobin can damage the kidney. We aimed to assess any subclinical renal injury in G6PD children. Methods Sixty children were included. Thirty G6PD deficiency anemia children were enrolled during the acute hemolytic crisis and after the hemolytic episode had elapsed. Another thirty healthy children were included as controls. Serum cystatin C, creatinine levels, and urinary albumin/creatinine (A/C) ratio were measured, and the glomerular filtration rate (GFR) was calculated. Results Significantly higher urinary A/C ratio (p=0.001,0.002 respectively) and lower GFR (p=0.001 for both) were found during hemolysis and after the hemolytic episode compared to the controls. Also, significant higher serum cystatin C (p=0.001), creatinine (p=0.05) and A/C (p= 0.001) ratio and insignificant lower GFR (p=0.3) during acute hemolytic crisis compared to the same children after the hemolytic episode subsided. Conclusions G6PD deficiency anemia is associated with a variable degree of acute renal injury during acute hemolytic episodes which may persist after elapsing of the hemolytic crises.

  8. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury.

    PubMed

    Palevsky, Paul M; Liu, Kathleen D; Brophy, Patrick D; Chawla, Lakhmir S; Parikh, Chirag R; Thakar, Charuhas V; Tolwani, Ashita J; Waikar, Sushrut S; Weisbord, Steven D

    2013-05-01

    In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.

  9. Classical and remote post-conditioning effects on ischemia/reperfusion-induced acute oxidant kidney injury.

    PubMed

    Kadkhodaee, Mehri; Najafi, Atefeh; Seifi, Behjat

    2014-11-01

    The present study aimed to analyze and compare the effects of classical and remote ischemic postconditioning (POC) on rat renal ischemia/reperfusion (IR)-induced acute kidney injury. After right nephrectomy, male rats were randomly assigned into four groups (n = 8). In the IR group, 45 min of left renal artery occlusion was induced followed by 24 h of reperfusion. In the classical POC group, after induction of 45 min ischemia, 4 cycles of 10 s of intermittent ischemia and reperfusion were applied to the kidney before complete restoring of renal blood. In the remote POC group, 4 cycles of 5 min ischemia and reperfusion of left femoral artery were applied after 45 min renal ischemia and right at the time of renal reperfusion. There was a reduction in renal function (increase in blood urea and creatinine) in the IR group. Application of both forms of POC prevented the IR-induced reduction in renal function and histology. There were also significant improvements in kidney oxidative stress status in both POC groups demonstrated by a reduction in malondialdehyde (MDA) formation and preservation of antioxidant levels comparing to the IR group. We concluded that both methods of POC have protective effects on renal function and histology possibly by a reduction in IR-induced oxidative stress.

  10. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.

    PubMed

    Gupta, Kamlesh K; Donahue, Deborah L; Sandoval-Cooper, Mayra J; Castellino, Francis J; Ploplis, Victoria A

    2015-01-01

    Sepsis-induced acute kidney injury (AKI) contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1) and vitronectin (Vn) are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1-/-) or expressing a PAI-1-mutant (PAI-1R101A/Q123K) in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1-/- and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT) mice after LPS challenge. Also, PAI-1-/- mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC) in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.

  11. Quantification and localization of M2 macrophages in human kidneys with acute tubular injury

    PubMed Central

    Palmer, Matthew B; Vichot, Alfred A; Cantley, Lloyd G; Moeckel, Gilbert W

    2014-01-01

    This study addresses for the first time the question whether there is significant macrophage population in human kidney sections from patients with acute tubular injury (ATI). We examined therefore the interstitial macrophage population in human kidney tissue with biopsy-proven diagnosis of ATI, minimal change disease (MCD), and MCD with ATI. Kidney biopsies from patients with the above diagnoses were stained with antibodies directed against CD68 (general macrophage marker), CD163 (M2 marker), and HLA-DR (M1 marker) and their respective electron microscopy samples were evaluated for the presence of interstitial macrophages. Our study shows that patients with ATI have significantly increased numbers of interstitial CD68+ macrophages, with an increase in both HLA-DR+ M1 macrophages and CD163+ M2 macrophages as compared to patients with MCD alone. Approximately 75% of macrophages were M2 (CD163+) whereas only 25% were M1 (HLA-DR+). M2 macrophages, which are believed to be critical for wound healing, were found to localize close to the tubular basement membrane of injured proximal tubule cells. Ultra structural examination showed close adherence of macrophages to the basement membrane of injured tubular epithelial cells. We conclude that macrophages accumulate around injured tubules following ATI and exhibit predominantly an M2 phenotype. We further speculate that macrophage-mediated repair may involve physical contact between the M2 macrophage and the injured tubular epithelial cell. PMID:25404860

  12. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    PubMed

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis. PMID:25830761

  13. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    PubMed

    Leventhal, Jeremy S; Ni, Jie; Osmond, Morgan; Lee, Kyung; Gusella, G Luca; Salem, Fadi; Ross, Michael J

    2016-01-01

    Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO). Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3) and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  14. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression

    PubMed Central

    Leventhal, Jeremy S.; Ni, Jie; Osmond, Morgan; Lee, Kyung; Gusella, G. Luca; Salem, Fadi; Ross, Michael J.

    2016-01-01

    Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO). Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3) and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling. PMID:26990086

  15. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    PubMed

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.

  16. Major comorbid disease processes associated with increased incidence of acute kidney injury

    PubMed Central

    Farooqi, Salwa; Dickhout, Jeffrey G

    2016-01-01

    Acute kidney injury (AKI) is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment. Some of the most common co-morbid disease processes that increase the risk of AKI are diabetes, cancer, cardiac surgery and human immunodeficiency virus (HIV) acquired immune deficiency syndrome (AIDS). This review article identifies the increased risk of acquiring AKI with given co-morbid diseases. Furthermore, the pathophysiological mechanisms underlying AKI in relation to co-morbid diseases are discussed to understand how the risk of acquiring AKI is increased. This paper reviews the effects of various co-morbid diseases including: Diabetes, cancer, cardiovascular disease and HIV AIDS, which all exhibit a significant increased risk of developing AKI. Amongst these co-morbid diseases, inflammation, the use of nephrotoxic agents, and hypoperfusion to the kidneys have been shown to be major pathological processes that predisposes individuals to AKI. The pathogenesis of kidney injury is complex, however, effective treatment of the co-morbid disease processes may reduce its risk. Therefore, improved management of co-morbid diseases may prevent some of the underlying pathology that contributes to the increased risk of developing AKI. PMID:26981437

  17. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    PubMed

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery.

  18. Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris.

    PubMed

    Ryan, Margaret; Lazar, Ira; Nadasdy, Gyongyi M; Nadasdy, Tibor; Satoskar, Anjali A

    2015-03-01

    Acute tubular necrosis (ATN), especially from toxic injury is frequently accompanied by tubular casts and crystals. Myeloma casts, myoglobin, red blood cell and granular casts are well described. However, bile casts in tubules are rarely seen. We describe a case of Tribulus terrestris toxicity in a young healthy male, presenting with severe hyperbilirubinemia followed by acute renal failure and bile containing casts in the tubules. Tribulus terrestris is an herb often used by athletes as a nutritional supplement for performance enhancement. Although it is thought to be relatively safe, serious side effects have been reported before. Our aim is to increase awareness of the potential toxicities of performance enhancing herbal medications. These are often sold over-the-counter and therefore casually used, especially by young healthy individuals. Beneficial effects are controversial. Under-reporting by patients and infrequent documentation by health-care providers can delay diagnosis. We elaborately describe the kidney biopsy findings in Tribulus terrestris toxicity, and also provide a concise overview of the spectrum of tubular casts and their staining patterns, found in various kidney diseases.

  19. Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute Kidney Injury

    PubMed Central

    Sallustio, Fabio; Serino, Grazia; Schena, Francesco Paolo

    2015-01-01

    Abstract Human kidney is particularly susceptible to ischemia and toxins with consequential tubular necrosis and activation of inflammatory processes. This process can lead to the acute renal injury, and even if the kidney has a great capacity for regeneration after tubular damage, in several circumstances, the normal renal repair program may not be sufficient to achieve a successful regeneration. Resident adult renal stem/progenitor cells could participate in this repair process and have the potentiality to enhance the renal regenerative mechanism. This could be achieved both directly, by means of their capacity to differentiate and integrate into the renal tissues, and by means of paracrine factors able to induce or improve the renal repair or regeneration. Recent genetic fate-tracing studies indicated that tubular damage is instead repaired by proliferative duplication of epithelial cells, acquiring a transient progenitor phenotype and by fate-restricted clonal cell progeny emerging from different nephron segments. In this review, we discuss about the properties and the reparative characteristics of high regenerative CD133+/CD24+ cells, with a view to a future application of these cells for the treatment of acute renal injury. PMID:26309808

  20. NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis

    PubMed Central

    Shen, Jianxiao; Wang, Ling; Jiang, Na; Mou, Shan; Zhang, Minfang; Gu, Leyi; Shao, Xinghua; Wang, Qin; Qi, Chaojun; Li, Shu; Wang, Wanpeng; Che, Xiajing; Ni, Zhaohui

    2016-01-01

    Iodinated contrast media serves as a direct causative factor of acute kidney injury (AKI) and is involved in the progression of cellular dysfunction and apoptosis. Emerging evidence indicates that NLRP3 inflammasome triggers inflammation, apoptosis and tissue injury during AKI. Nevertheless, the underlying renoprotection mechanism of NLRP3 inflammasome against contrast-induced AKI (CI-AKI) was still uncertain. This study investigated the role of NLRP3 inflammasome in CI-AKI both in vitro and in vivo. In HK-2 cells and unilateral nephrectomy model, NLRP3 and NLRP3 inflammasome member ASC were significantly augmented with the treatment of contrast media. Moreover, genetic disruption of NLRP3 notably reversed contrast-induced expression of apoptosis related proteins and secretion of proinflammatory factors, similarly to the effects of ASC deletion. Consistent with above results, absence of NLRP3 in mice undergoing unilateral nephrectomy also protected against contrast media-induced renal cells phenotypic alteration and cell apoptosis via modulating expression level of apoptotic proteins. Collectively, we demonstrated that NLRP3 inflammasome mediated CI-AKI through modulating the apoptotic pathway, which provided a potential therapeutic target for the treatment of contrast media induced acute kidney injury. PMID:27721494

  1. Multidimensional Approach to Adequacy of Renal Replacement Therapy in Acute Kidney Injury.

    PubMed

    Villa, Gianluca; Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2016-01-01

    Acute kidney injury (AKI) is frequently observed among hospitalized and critical care patients. In the absence of any effective therapies aiming to actively restore kidney function, AKI is usually managed through acute renal replacement therapy (ARRT). 'Optimization' of ARRT may reduce the mortality of patients with AKI. Although several studies have tried to identify the most adequate approach to ARRT in terms of dose, treatment modality and all other important dimensions, the literature has provided controversial results. Nowadays, adequate ARRT still appears difficult to dose, prescribe, deliver and monitor among different critical care patients. The identification of the major elements involved for a multidimensional approach to adequacy of ARRT in patients with AKI should consider the patient, the applied technology and the environment. All these aspects should be carefully evaluated and adequately applied in clinical practice through a patient-oriented approach. Adequacy of ARRT imposes the concomitant consideration of more complex issues, such as the timing, modality and technique of ARRT delivery; anticoagulation and substitution fluid choice; membrane selection; monitor accuracy; the role of fluid overload; and other patient comorbidities. The capacity of clinicians to consider all these aspects through a multidimensional approach, adapting the different dimensions of ARRT to actual patients' needs, might be the fundamental missing element in the pathway toward significant outcome improvements among critically ill patients with AKI. This narrative review provides a systematic approach to the major dimensions of ARRT and their multidimensional rationalization for adequate treatment prescription, monitoring and evaluation. PMID:26881756

  2. Melatonin protects kidney against apoptosis induced by acute unilateral ureteral obstruction in rats

    PubMed Central

    Badem, Hüseyin; Cakmak, Muzaffer; Yilmaz, Hakki; Kosem, Bahadir; Karatas, Omer Faruk; Bayrak, Reyhan; Cimentepe, Ersin

    2016-01-01

    Introduction To investigate whether there was a protective effect of melatonin on apoptotic mechanisms after an acute unilateral obstruction of the kidney. Material and methods A total of 25 rats consisting of five groups were used in the study, designated as follows: Group 1: control, Group 2: sham, Group 3: unilateral ureteral obstruction treated with only saline, Group 4: unilateral ureteral obstruction treated with melatonin immediately, and Group 5: unilateral obstruction treated with melatonin one day after obstruction. Melatonin was administered as a 10 mg/kg dose intraperitoneally. The kidneys were evaluated according to the apoptotic index and Ki-67 scores. Results Comparison of all obstruction groups (Group 3, 4, and 5), revealed that the apoptotic index was significantly higher in Groups 1 and 2. Despite melatonin reduced apoptotic mechanisms in Groups 4 and 5, there was no significant difference between Groups 4 and 5 in terms of the reduction of apoptosis. However, the reduction of apoptosis in the melatonin treated group did not decrease to the level of Groups 1 and 2. Conclusions Despite melatonin administration, which significantly reduces the apoptotic index occurring after acute unilateral ureteral obstruction, the present study did not observe a return to normal renal histology in the obstruction groups. PMID:27551563

  3. A Case of Primary Hypoparathyroidism Presenting with Acute Kidney Injury Secondary to Rhabdomyolysis

    PubMed Central

    Aydin, Zeki; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Cebeci, Egemen; Ozturk, Savas; Kazancioglu, Rumeyza

    2016-01-01

    Hypoparathyroidism is the most common cause of symmetric calcification of the basal ganglia. Herein, a case of primary hypoparathyroidism with severe tetany, rhabdomyolysis, and acute kidney injury is presented. A 26-year-old male was admitted to the emergency clinic with leg pain and cramps, nausea, vomiting, and decreased amount of urine. He had been treated for epilepsy for the last 10 years. He was admitted to the emergency department for leg pain, cramping in the hands and legs, and agitation multiple times within the last six months. He was prescribed antidepressant and antipsychotic medications. He had a blood pressure of 150/90 mmHg, diffuse abdominal tenderness, and abdominal muscle rigidity on physical examination. Pathological laboratory findings were as follows: creatinine, 7.5 mg/dL, calcium, 3.7 mg/dL, alanine transaminase, 4349 U/L, aspartate transaminase, 5237 U/L, creatine phosphokinase, 262.000 U/L, and parathyroid hormone, 0 pg/mL. There were bilateral symmetrical calcifications in basal ganglia and the cerebellum on computerized tomography. He was diagnosed as primary hypoparathyroidism and acute kidney injury secondary to severe rhabdomyolysis. Brain calcifications, although rare, should be considered in dealing with patients with neurological symptoms, symmetrical cranial calcifications, and calcium metabolism abnormalities. PMID:27034860

  4. Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass

    PubMed Central

    Wang, Xiaocou; Xue, Qinghua; Yan, Fuxia; Liu, Jinping; Li, Shoujun; Hu, Shengshou

    2015-01-01

    Objective Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass. Methods Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected. Results The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation

  5. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

    SciTech Connect

    Zhou, Xiaobing; Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng; Li, Bo

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.

  6. Acute renal failure and volume overload syndrome secondary to a femorofemoral arteriovenous fistula angioplasty in a kidney transplant recipient.

    PubMed

    Bertrand, Dominique; Desbuissons, Geoffroy; Pallet, Nicolas; Sartorius, Albane; Legendre, Christophe; Mamzer, Marie-France; Sberro Soussan, Rebecca

    2013-01-01

    Experimental and clinical studies analyzing the impact of AVF on cardiovascular and renal parameters, as well as outcomes, in kidney transplant recipients are lacking. On the other hand, it is not known whether AVF ligation after transplantation modifies hemodynamic parameters and kidney function. We report a case of a renal transplant recipient who developed an acute congestive heart failure accompanied by renal failure, which were triggered by femorofemoral AVF angioplasty. Prompt AVF ligation rapidly reversed clinical symptoms and normalized cardiac and renal functions. This paper illustrates the potential deleterious consequences of high-output AVF after kidney transplantation and raises considerations regarding the impact of the fistula on cardiac status and kidney function after kidney transplantation and, consequently, the management AVF after transplantation. PMID:23533921

  7. Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

    PubMed

    Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2016-03-01

    Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective

  8. Diagnostic accuracy of urinary neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury

    PubMed Central

    Patel, Munna Lal; Sachan, Rekha; Shyam, Radhey; Kumar, Satish; Kamal, Ritul; Misra, Arvind

    2016-01-01

    Background Sepsis is the most common cause of acute kidney injury (AKI). Very few studies have investigated the predictive properties of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a marker of AKI in septic patients. The aim of this study is to examine uNGAL in septic patients with and without AKI and to evaluate its predictive value. Methods We prospectively studied 155 patients with sepsis over a period of 1 year. Urine was analyzed for neutrophil gelatinase-associated lipocalin at 12, 24, and 48 hours after admission. Patients with <24-hour stay and those with chronic kidney disease were excluded. AKI was classified according to the Acute Kidney Injury Network guidelines. Results The differences in mean change of uNGAL at 12, 24, and 48 hours were 80.00±7.00 ng/mL and 128.13±22.46 ng/mL, respectively in septic AKI, and 02.07±0.80 ng/mL and 26.13±15.12 ng/mL, respectively in septic non-AKI. At baseline or 12 hours, the cutoff value of 34.32 ng/mL had a sensitivity and specificity of 86.36 and 80.60, respectively and an area under curve of 0.81 (95% CI: 0.73–0.89) for predicting AKI. At the cutoff value 199.99 ng/mL sensitivity and specificity of 90.0 and 64.66, respectively and an area under curve of 0.82 (95% CI, 0.75–0.88) for predicting AKI. Conclusion The baseline or 12-hour uNGAL is highly sensitive but a less specific predictor of AKI in septic patients. PMID:27471404

  9. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    PubMed

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-01-01

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury. PMID:26691774

  10. Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury.

    PubMed

    Skrypnyk, Nataliya I; Voziyan, Paul; Yang, Haichun; de Caestecker, Christian R; Theberge, Marie-Claude; Drouin, Mathieu; Hudson, Billy; Harris, Raymond C; de Caestecker, Mark P

    2016-08-01

    Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI. PMID:27194713

  11. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    PubMed Central

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206

  12. Early subclinical coronary artery calcification in young adults who were pediatric kidney transplant recipients.

    PubMed

    Ishitani, Michael B; Milliner, Dawn S; Kim, Dean Y; Bohorquez, Humberto E; Heimbach, Julie K; Sheedy, Patrick F; Morgenstern, Bruce Z; Gloor, James M; Murphy, Joseph G; McBane, Robert D; Bielak, Lawrence F; Peyser, Patricia A; Stegall, Mark D

    2005-07-01

    Coronary artery disease (CAD) is the leading cause of death in adults after successful kidney transplantation. Children who have undergone successful kidney transplantation are entering young adulthood; however, the prevalence and extent of CAD in this population is unknown. We conducted a pilot study in young adults with stable allograft function, who received kidney transplants as children to measure coronary artery calcification (CAC), a marker of coronary artery atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric kidney transplantation for known CAD risk factors; these patients underwent noninvasive imaging with electron-beam computed tomography (EBCT) for measurement of CAC. Prevalence and quantity of CAC were then compared to asymptomatic individuals from the community. All patients had multiple risk factors for CAD. Mean age at evaluation was 32 years (range: 21-48 years). CAC is uncommon in individuals in the community in this age range; however, nearly half of our patients had CAC detected with the quantity of CAC comparable to asymptomatic individuals from the community 10-40 years older. These data suggest young adults who received pediatric kidney transplants are at increased risk for developing early CAC and need close monitoring to detect early CAD so as to prevent premature cardiac morbidity and mortality. PMID:15943627

  13. Emerging Biomarkers and Metabolomics for Assessing Toxic Nephropathy and Acute Kidney Injury (AKI) in Neonatology

    PubMed Central

    Mussap, M.; Noto, A.; Fanos, V.; Van Den Anker, J. N.

    2014-01-01

    Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called “omics” allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS), proton nuclear magnetic resonance (1H NMR), and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods. PMID:25013791

  14. The Association of Acute Kidney Injury and Atrial Fibrillation after Cardiac Surgery in an Asian Prospective Cohort Study.

    PubMed

    Ng, Roderica Rui Ge; Tan, Gabriel Hong Jie; Liu, Weiling; Ti, Lian Kah; Chew, Sophia Tsong Huey

    2016-03-01

    Acute kidney injury (AKI) and atrial fibrillation (AF) after cardiac surgery are common occurrences and increase patient morbidity and mortality. Inflammation plays a role in increased incidence of AF in patients with chronic kidney disease (CKD); reactive oxygen species and inflammatory markers which are increased in patients with CKD were found to affect the proper functioning of the intracellular ion channels, connexions (transmembrane proteins found in intercellular gap junctions), and electrical homogeneity of the extracellular matrix which are essential for electrical stability and proper conduction of electrical impulses in the atrium. However, it is not known if similar mechanisms are also involved in AKI. We tested the hypothesis that patients with AKI after cardiac surgery have a higher incidence of postoperative AF.Data from 2885 patients, who had undergone cardiac surgery between August 2008 and July 2012 from the Singapore's 2 major heart centers, were obtained prospectively. Postoperative AKI was defined using the Acute Kidney Injury Network criteria. The primary outcome was postoperative AF, and subjects were considered to have postoperative AF if the AF lasted more than an hour, affected hemodynamics, or required medical treatment.The incidence of AKI was 29.7% and the incidence of postoperative AF was 16.8%. A total of 27.7% of AKI patients developed AF. Patients with AKI had a 2-fold increased risk of developing AF (relative risk [RR], 1.716; 95% confidence interval [CI], 1.433-2.055; P < 0.001). The following factors were found to independently increase the risk of AF in patients with AKI: age (RR, 1.011; 95% CI, 1.000-1.022; P = 0.04), low preoperative hemoglobin (RR, 0.942; 95% CI, 0.888-1.000; P = 0.05), low preoperative estimated glomerular filtration rate (eGFR) (RR, 0.987; 95% CI, 0.980-0.994; P < 0.001), and lowest hematocrit during bypass (RR, 0.943; 95% CI, 0.910-0.978; P < 0.001).Patients with AKI are more likely to

  15. The significance of tubular and glomerular proteinuria in critically ill patients with severe acute kidney injury

    PubMed Central

    Lim, Christopher Thiam Seong; Tan, Han Khim; Lau, Yeow Kok

    2014-01-01

    Objective: Critically ill patients with acute kidney injury (AKI) frequently need acute renal replacement therapy (aRRT). We evaluated an inexpensive, rapid quantitative and qualitative analysis of proteinuria on the course of AKI patients requiring aRRT in intensive care. Method: This was a prospective, observational study of critically ill patients with severe established AKI or Acute on Chronic Kidney Injury (AoCKI) requiring aRRT. Urine samples were analyzed using Sodium-Dodecyl-Sulphate-Polyacryamide Gel Electrophoresis (SDS-PAGE). Results: A total of 30 critically ill patients were studied. Those who died have higher APACHE II (29 ± 6 vs. 20 ± 5, p<0.001), multi-organ failure (0.7 ± 0.5 vs. 0.2 ± 0.4, p < 0.02) and Tubular/Glomerular ratio (114 ± 60 vs. 75± 37, p < 0.05).The renal non-recoverers have higher baseline creatinine (415 ± 328 vs. 125± 19 umol/l, p < 0.01), urinary Dipstick value (1.8±0.8 vs. 0.5±0, p <0.05) and Glomerular score (3.0 ± 1.8 vs. 0.6 ± 0.2, p < 0.02).Heavy tubular proteinuria also predicts a longer duration of interim dialysis support and mortality whereas glomerular proteinuria correlates with development of chronicity and End Stage Renal Disease (ESRD). Conclusions: The dominant presence of tubular proteinuria is associated with poor survival in patients who have high APACHE II score and multi-organ failure. It also correlates with a longer duration of dialysis support in survivals. Renal Non-recoverers had heavy dominant presence of glomerular proteinuria. SDS-PAGE proteinuria analysis offers a reliable and inexpensive method to prognosticate proteinuria in this group of critically ill patients. PMID:25674105

  16. Amelioration of Acute Kidney Injury in Lipopolysaccharide-Induced Systemic Inflammatory Response Syndrome by an Aldose Reductase Inhibitor, Fidarestat

    PubMed Central

    Takahashi, Kazunori; Mizukami, Hiroki; Kamata, Kosuke; Inaba, Wataru; Kato, Noriaki; Hibi, Chihiro; Yagihashi, Soroku

    2012-01-01

    Background Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism. Methods Mice were injected with LPS and the effects of AR inhibitor (Fidarestat 32 mg/kg) before or after LPS injection were examined for the mortality, severity of renal failure and kidney pathology. Serum concentrations of cytokines (interleukin-1β, interleukin-6, monocyte chemotactic protein-1 and tumor necrosis factor-α) and their mRNA expressions in the lung, liver, spleen and kidney were measured. We also evaluated polyol metabolites in the kidney. Results Mortality rate within 72 hours was significantly less in LPS-injected mice treated with AR inhibitor both before (29%) and after LPS injection (40%) than untreated mice (90%). LPS-injected mice showed marked increases in blood urea nitrogen, creatinine and cytokines, and AR inhibitor treatment suppressed the changes. LPS-induced acute kidney injury was associated with vacuolar degeneration and apoptosis of renal tubular cells as well as infiltration of neutrophils and macrophages. With improvement of such pathological findings, AR inhibitor treatment suppressed the elevation of cytokine mRNA levels in multiple organs and renal sorbitol accumulation. Conclusion AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality. PMID:22253906

  17. Novelties in the early management of acute heart failure syndromes.

    PubMed

    Salem, Reda; Sibellas, Franck; Socrates, Thenral; Arenja, Nisha; Yilmaz, Mehmet Birhan; Mueller, Christian; Mebazaa, Alexandre

    2010-07-22

    The recent European Society of Cardiology (ESC) guidelines delineate the diagnosis and management of distinct categories of acute heart failure syndromes. However, physicians dealing with these patients may need guidance in choosing therapeutic alternatives as soon as the dyspneic patient arrives at the emergency department, until distinct categories of the ESC guidelines are identified. Hence, this manuscript summarizes practical recommendations for the very early management of patients with acute heart failure syndromes. The recommendations are based on a clinical classification system considering the initial systolic blood pressure and other symptoms. Early initiation of diagnostic and goal-directed treatment strategies are key factors in improving patient outcomes. Early and frequent reassessment is also imperative so that adjustments to the initial therapeutic approach can be made, as clinically indicated.

  18. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    SciTech Connect

    Chen, Jiao; Shetty, Sreerama; Zhang, Ping; Gao, Rong; Hu, Yuxin; Wang, Shuxia; Li, Zhenyu; Fu, Jian

    2014-06-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.

  19. Effects of Schizolobium parahyba Extract on Experimental Bothrops Venom-Induced Acute Kidney Injury

    PubMed Central

    Martines, Monique Silva; Mendes, Mirian M.; Shimizu, Maria H. M.; Melo Rodrigues, Veridiana; de Castro, Isac; Filho, Sebastião R. Ferreira; Malheiros, Denise M. A. C.; Yu, Luis; Burdmann, Emmanuel A.

    2014-01-01

    Background Venom-induced acute kidney injury (AKI) is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP) extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV)-induced AKI. Methodology Groups of 8 to 10 rats received infusions of 0.9% saline (control, C), SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T) in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Doppler), blood pressure (BP, intra-arterial transducer), renal vascular resistance (RVR), urinary osmolality (UO, freezing point), urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA]), lactate dehydrogenase (LDH, kinetic method), hematocrit (Hct, microhematocrit), fibrinogen (Fi, Klauss modified) and blinded renal histology (acute tubular necrosis score). Principal Findings BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. Conclusion SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR. PMID:24551041

  20. Effects of TORC1 Inhibition during the Early and Established Phases of Polycystic Kidney Disease

    PubMed Central

    Ta, Michelle H. T.; Schwensen, Kristina G.; Foster, Sheryl; Korgaonkar, Mayuresh; Ozimek-Kulik, Justyna E.; Phillips, Jacqueline K.; Peduto, Anthony; Rangan, Gopala K.

    2016-01-01

    The disease-modifying effects of target of rapamycin complex 1 (TORC1) inhibitors during different stages of polycystic kidney disease (PKD) are not well defined. In this study, male Lewis Polycystic Kidney Disease (LPK) rats (a genetic ortholog of human NPHP9, phenotypically characterised by diffuse distal nephron cystic growth) and Lewis controls received either vehicle (V) or sirolimus (S, 0.2 mg/kg by intraperitoneal injection 5 days per week) during the early (postnatal weeks 3 to 10) or late stages of disease (weeks 10 to 20). In early-stage disease, sirolimus reduced kidney enlargement (by 63%), slowed the rate of increase in total kidney volume (TKV) in serial MRI by 78.2% (LPK+V: 132.3±59.7 vs. LPK+S: 28.8±12.0% per week) but only partly reduced the percentage renal cyst area (by 19%) and did not affect the decline in endogenous creatinine clearance (CrCl) in LPK rats. In late-stage disease, sirolimus reduced kidney enlargement (by 22%) and the rate of increase in TKV by 71.8% (LPK+V: 13.1±6.6 vs. LPK+S: 3.7±3.7% per week) but the percentage renal cyst area was unaltered, and the CrCl only marginally better. Sirolimus reduced renal TORC1 activation but not TORC2, NF-κB DNA binding activity, CCL2 or TNFα expression, and abnormalities in cilia ultrastructure, hypertension and cardiac disease were also not improved. Thus, the relative treatment efficacy of TORC1 inhibition on kidney enlargement was consistent at all disease stages, but the absolute effect was determined by the timing of drug initiation. Furthermore, cystic microarchitecture, renal function and cardiac disease remain abnormal with TORC1 inhibition, indicating that additional approaches to normalise cellular dedifferentiation, inflammation and hypertension are required to completely arrest the progression of PKDs. PMID:27723777

  1. [Globosides as key players in the pathophysiology of Shiga toxin-associated acute kidney failure and Fabry disease].

    PubMed

    Porubsky, S

    2014-11-01

    Globosides and their isomeric counterparts isoglobosides belong to the class of neutral glycosphingolipids with an as yet undefined physiological function. In the pathogenesis of human diseases, globosides play an important role as cellular receptors for Shiga toxins which are produced by certain strains of S. dysenteriae and E. coli. In order to elucidate the pathogenesis of Shiga toxin-associated kidney failure, we studied human kidney biopsies and animal models. Our work showed that in patients suffering from Shiga toxin-elicited kidney failure, no complement activation could be demonstrated by immunohistochemical analysis of kidney biopsies. Therefore, complement activation is unlikely to play a major role in mediating thrombotic microangiopathy on exposure to Shiga toxin. Moreover, analysis of the human biopsies and of a murine model of Shiga toxin-associated disease pinpointed acute tubular damage as an important and previously neglected contributor to acute kidney failure in patients infected with Shiga toxin-producing E. coli. Furthermore, globosides play a decisive role in the pathogenesis of Fabry disease which results from a decreased or absent activity of the lysosomal enzyme α-galactosidase A. The results on transgenic mice showed that in vital organs, such as the heart, kidneys and liver, it was possible to revert the phenotype of Fabry disease by eliminating the synthesis of globosides. This implicates that substrate reduction therapy through inhibition of globosides might represent a new therapeutic option for Fabry disease, all the more so as globosides seem to be dispensable.

  2. Estimation of Early Postmortem Interval Through Biochemical and Pathological Changes in Rat Heart and Kidney.

    PubMed

    Abo El-Noor, Mona Mohamed; Elhosary, Naema Mahmoud; Khedr, Naglaa Fathi; El-Desouky, Kareema Ibraheem

    2016-03-01

    Accurate estimation of time passed since death is a complicated task in forensic medicine especially in homicide or unwitnessed death investigations. Changes in oxidant/antioxidant parameters were investigated if it can be relied upon in estimating the early postmortem interval (EPI) in rat heart and kidney, and whether these changes were correlated with histopathological findings in these tissues. Heart and kidney tissues of 84 male albino rats were divided into 2 parts. One part used for estimation of levels of malondialdehyde (MDA), nitric oxide (NO), and total thiol as well as the activity of glutathione reductase (GR), glutathione S transferase, and catalase. The second part was examined histopathologically. It was found that MDA and NO were significantly increased earlier in the heart than kidney tissues. Meanwhile, total thiol, catalase, glutathione S transferase, and GR were commenced to be significantly decreased in the heart before kidney tissues. Linear regression analysis of independent variables of heart was found to be of a high predictive value of 97.2% (EPI = 8.607 - 0.240 GR + 0.002 MDA + 0.014 NO). Structural deterioration of heart started 3 to 4 hours compared with renal sections that began 5 to 6 hours after death. The relationship between oxidant and antioxidant parameters is crucial in determining the EPI. The kidney was found to be more resistible to oxidative damage. Further research on humans is needed.

  3. High Risk of Herpes Zoster among Patients with Advance Acute Kidney Injury--A Population-Based Study.

    PubMed

    Yang, Wei-Shun; Hu, Fu-Chang; Chen, Meng-Kan; Ko, Wen-Je; Chen, Likwang; Wu, Kwan-Dun; Wu, Vin-Cent

    2015-09-03

    The risk for herpes zoster (HZ) in acute kidney injury (AKI) survivors was never explored. We identified 2,387 adults in the Taiwan National Health Insurance Research Database who recovered from dialysis-requiring AKI and matched them with non-recovery and non-AKI patients by propensity score. During a mean follow-up of 2.7 years, the incidences of HZ were 6.9, 8.2 and 4.8 episodes per 1,000 person-years in AKI-non-recovery, AKI-recovery and non-AKI group, respectively. The recovery group was more likely to develop herpes zoster than those without acute kidney injury [incidence-rate ratios 1.71, 95% confidence interval 1.16-2.52; p = 0.007]. Patients without acute kidney injury were less likely to develop herpes zoster than those AKI, recovered from dialysis or not (hazard ratio HR 0.66, 95% CI 0.46-0.95). Dialysis-requiring acute kidney injury poses a long-term risk of herpes zoster after hospital discharge. Even patients who have recovered from dialysis still carry a significantly higher risk of developing herpes zoster.

  4. Back to Basics: Is There a Good Reason to Not Systematically Measure Urine Creatinine in Acute Kidney Injury Monitoring?

    PubMed

    Maciel, Alexandre Toledo

    2016-01-01

    Regardless of the recent advancements in the understanding of the pathophysiology of acute kidney injury (AKI), its diagnosis remains fundamentally dependent on the serum creatinine (sCr) level and urine output (UO), both of which are considered late markers of AKI, offering only a vague idea of the actual creatinine clearance (CrCl). Although not ideal, CrCl is still the most common alternative of the glomerular filtration rate (GFR) in clinical practice. It is generally accepted that early diagnosis of AKI must reveal kidney impairment before sCr increases. Much effort has been made to find tubular and glomerular markers of injury which increase (in blood and/or in urine) before the 'official' diagnosis of AKI. Most of these markers are expensive and not widely available, especially in developing countries. Urine creatinine (CrU), the major link between sCr and UO, has been systematically ignored and clinicians are usually unaware of its value. The reasons for this are unclear, but it may be related to the lack of a reference range, dependence of its concentration value on the urine flow (which in turn is only adequately assessed with an indwelling urinary catheter) and the clinical unavailability of its counterbalance part - creatinine production. Changes in urine tend to precede changes in blood in the course of AKI development and recovery. Hence, it is important to bear in mind that changes in sCr signal renal dysfunction with a significant delay. The search for a more dynamic, 'real-time' but pragmatic assessment of renal function, especially in patients at risk of abrupt decrease in GFR is certainly one of the most relevant focus of research in the field of AKI monitoring. Systematic CrU assessment may be highly relevant in this case. PMID:27270242

  5. Role of biomarkers of nephrotoxic acute kidney injury in deliberate poisoning and envenomation in less developed countries

    PubMed Central

    Mohamed, Fahim; Endre, Zoltan H; Buckley, Nicholas A

    2015-01-01

    Acute kidney injury (AKI) has diverse causes and is associated with increased mortality and morbidity. In less developed countries (LDC), nephrotoxic AKI (ToxAKI) is common and mainly due to deliberate ingestion of nephrotoxic pesticides, toxic plants or to snake envenomation. ToxAKI shares some pathophysiological pathways with the much more intensively studied ischaemic AKI, but in contrast to ischaemic AKI, most victims are young, previously healthy adults. Diagnosis of AKI is currently based on a rise in serum creatinine. However this may delay diagnosis because of the kinetics of creatinine. Baseline creatinine values are also rarely available in LDC. Novel renal injury biomarkers offer a way forward because they usually increase more rapidly in AKI and are normally regarded as absent or very low in concentration, thereby reducing the need for a baseline estimate. This should increase sensitivity and speed of diagnosis. Specificity should also be increased for urine biomarkers since many originate from the renal tubular epithelium. Earlier diagnosis of ToxAKI should allow earlier initiation of appropriate therapy. However, translation of novel biomarkers of ToxAKI into clinical practice requires better understanding of non-renal factors in poisoning that alter biomarkers and the influence of dose of nephrotoxin on biomarker performance. Further issues are establishing LDC population-based normal ranges and assessing sampling and analytical parameters for low resource settings. The potential role of renal biomarkers in exploring ToxAKI aetiologies for chronic kidney disease of unknown origin (CKDu) is a high research priority in LDC. Therefore, developing more sensitive biomarkers for early diagnosis of nephrotoxicity is a critical step to making progress against AKI and CKDu in the developing world. PMID:26099916

  6. Incidence, Predictors, and Impact on Hospital Mortality of Amphotericin B Nephrotoxicity Defined Using Newer Acute Kidney Injury Diagnostic Criteria

    PubMed Central

    Kobayashi, Carla Dinamérica; de Carvalho Almeida, Luna; de Oliveira dos Reis, Camilla; Santos, Barbara Mendes; Glesby, Marshall Jay

    2015-01-01

    Studies on amphotericin B (AmB) nephrotoxicity use diverse definitions of acute kidney injury (AKI). Here, we used the new Kidney Disease Improving Global Outcome (KDIGO) system to describe the incidence, predictors, and impact of AmB-induced AKI on hospital mortality in 162 patients treated with AmB (120 with deoxycholate preparation and 42 with liposomal preparation). KDIGO stage 1 requires an absolute increase of ≥0.3 mg/dl or ≥1.5× over baseline serum creatinine (SCr), while stage 2 requires ≥2×, and stage 3 requires ≥3×. A binary KDIGO definition (KDIGObin) corresponds to stage ≥1. For comparison, we included two definitions of AKI traditionally utilized in nephrotoxicity studies: ≥0.5 mg/dl (NT0.5) and ≥2× (NT2×) increase in baseline SCr. The overall incidence of AmB-induced AKI by KDIGObin was 58.6% (stage 1, 30.9%; stage 2, 18.5%; stage 3, 9.3%). Predictors of AKI by KDIGObin were older age and use of furosemide and angiotensin-converting enzyme inhibitor (ACE-I). Traditional criteria detected lower incidences of AKI, at 45.1% (NT0.5) and 27.8% (NT2×). Predictors of AKI by traditional criteria were older age and use of vancomycin (NT0.5) and use of vancomycin and vasopressors (NT2×). KDIGObin detected AKI 2 days earlier than the most sensitive traditional criterion. However, only traditional criteria were associated with intensive care unit (ICU) admission, mechanical ventilation, and mortality. In conclusion, the increase in sensitivity of KDIGObin is accompanied by a loss of specificity and ability to predict outcomes. Prospective studies are required to weigh the potential gain from early AKI detection against the potential loss from undue changes in management in patients with subtle elevations in SCr. PMID:26014956

  7. Moving beyond supportive care--current status of specific therapies in pediatric acute kidney injury.

    PubMed

    Symons, Jordan M

    2014-02-01

    Acute kidney injury (AKI) remains a significant challenge, leading to increased morbidity, mortality, and medical costs. Therapy for AKI to this point has largely been supportive; specific interventions to treat established AKI have had minimal effect. Review of the pathogenesis of AKI reveals complex, interacting mechanisms, including changes in microcirculation, the immune system, and inflammation, and cell death from both necrosis and apoptosis. Past definitions of AKI have been imprecise; newer methods for AKI identification and classification, including novel biomarkers and improved criteria for defining AKI, may permit earlier intervention with greater potential for success. With improved understanding of pathophysiology and the opportunity for intervention before AKI is fully established, clinicians may be able to move beyond supportive care and improve outcomes.

  8. Acute kidney injury after contrast-enhanced examination among elderly1

    PubMed Central

    Aoki, Beatriz Bonadio; Fram, Dayana; Taminato, Mônica; Batista, Ruth Ester Sayad; Belasco, Angélica; Barbosa, Dulce Aparecida

    2014-01-01

    OBJECTIVES: to assess renal function in elderly patients undergoing contrast-enhanced computed tomography and identify the preventive measures of acute kidney injury in the period before and after the examination. METHOD: longitudinal cohort study conducted at the Federal University of São Paulo Hospital, from March 2011 to March 2013. All hospitalized elderly, of both sexes, aged 60 years and above, who performed the examination, were included (n=93). We collected sociodemographic data, data related to the examination and to the care provided, and creatinine values prior and post exam. RESULTS: an alteration in renal function was observed in 51 patients (54%) with a statistically significant increase of creatinine values (p<0.04), and two patients (4.0%) required hemodialysis. CONCLUSION: There is an urgent need for protocols prior to and post contrast-enhanced examination in the elderly, and other studies to verify the prognosis of this population. PMID:25296148

  9. Heart block and acute kidney injury due to hyperparathyroidism-induced hypercalcemic crisis.

    PubMed

    Brown, Taylor C; Healy, James M; McDonald, Mary J; Hansson, Joni H; Quinn, Courtney E

    2014-12-01

    We describe a patient who presented with multi-system organ failure due to extreme hypercalcemia (serum calcium 19.8 mg/dL), resulting from primary hyperparathyroidism. He was found to have a 4.8 cm solitary atypical parathyroid adenoma. His course was complicated by complete heart block, acute kidney injury, and significant neurocognitive disturbances. Relevant literature was reviewed and discussed. Hyperparathyroidism-induced hypercalcemic crisis (HIHC) is a rare presentation of primary hyperparathyroidism and only a small minority of these patients develop significant cardiac and renal complications. In cases of HIHC, a multidisciplinary effort can facilitate rapid treatment of life-threatening hypercalcemia and definitive treatment by surgical resection. As such, temporary transvenous cardiac pacing and renal replacement therapy can provide a life-saving bridge to definitive parathyroidectomy in cases of HIHC.

  10. We Use Permcaths Instead of Peritoneal Catheters for Acute Kidney Injury and Urgent-Start Dialysis.

    PubMed

    Dean, Daniel; Cruz, Dinna N

    2016-07-01

    The rising tide of severe acute kidney injury requiring dialysis (AKI-D) and unplanned dialysis initiation for advanced CKD patients remains a major problem for the nephrology community worldwide. Hemodialysis (HD) through a central venous catheter remains the most common practice for both. Peritoneal dialysis (PD) remains greatly underutilized despite mounting evidence of equipoise with HD for a significant proportion of patients. PD is technically simpler, requires less infrastructure, and costs less. However, the structure of our healthcare system, hospital logistics, and the current state of nephrology training all contribute to the reflexive consult for a central venous catheter. As clinicians, we must ask ourselves if we are doing our patients and our healthcare system a disservice by not offering PD in AKI and urgent-start situations. PMID:27154837

  11. Urinary levels of early kidney injury molecules in children with vitamin B12 deficiency.

    PubMed

    Güneş, Ali; Aktar, Fesih; Tan, İlhan; Söker, Murat; Uluca, Ünal; Balık, Hasan; Mete, Nuriye

    2016-10-01

    The aim of this study was to investigate urine early kidney injury molecules, including human kidney injury molecule-1 (KIM-1), liver-type fatty-acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase A (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in children with vitamin B12 (cobalamin) deficiency (CD). Twelve children with vitamin B12 deficiency and 20 healthy matched controls were included. Hematologic parameters, serum urea, creatinine (Cr), electrolytes, B12 and folate levels were recorded. Estimated glomerular filtration rate (eGFR) was calculated. Urine protein, electrolytes, andurinary early markers were measured. Patients with CD had significantly higher urine electrolyte/Cr ratios (p <0.05). Significantly higher urinary KIM-1/Cr, L-FABP/Cr, NAG/Cr and NGAL/Cr were found in CD group (p <0.05). Significant negative correlations were found between levels of serum B12 and urinary markers in the patients (p <0.05). Increased urinary kidney injury molecules and electrolytes in children with B12 deficiency suggest a possible subclinical renal dysfunction, which cannot be determined by conventional kidney function tests.

  12. Urinary levels of early kidney injury molecules in children with vitamin B12 deficiency.

    PubMed

    Güneş, Ali; Aktar, Fesih; Tan, İlhan; Söker, Murat; Uluca, Ünal; Balık, Hasan; Mete, Nuriye

    2016-10-01

    The aim of this study was to investigate urine early kidney injury molecules, including human kidney injury molecule-1 (KIM-1), liver-type fatty-acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase A (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in children with vitamin B12 (cobalamin) deficiency (CD). Twelve children with vitamin B12 deficiency and 20 healthy matched controls were included. Hematologic parameters, serum urea, creatinine (Cr), electrolytes, B12 and folate levels were recorded. Estimated glomerular filtration rate (eGFR) was calculated. Urine protein, electrolytes, andurinary early markers were measured. Patients with CD had significantly higher urine electrolyte/Cr ratios (p <0.05). Significantly higher urinary KIM-1/Cr, L-FABP/Cr, NAG/Cr and NGAL/Cr were found in CD group (p <0.05). Significant negative correlations were found between levels of serum B12 and urinary markers in the patients (p <0.05). Increased urinary kidney injury molecules and electrolytes in children with B12 deficiency suggest a possible subclinical renal dysfunction, which cannot be determined by conventional kidney function tests. PMID:27606644

  13. Utilizing electronic health records to predict acute kidney injury risk and outcomes: workgroup statements from the 15(th) ADQI Consensus Conference.

    PubMed

    Sutherland, Scott M; Chawla, Lakhmir S; Kane-Gill, Sandra L; Hsu, Raymond K; Kramer, Andrew A; Goldstein, Stuart L; Kellum, John A; Ronco, Claudio; Bagshaw, Sean M

    2016-01-01

    The data contained within the electronic health record (EHR) is "big" from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider how best to approach AKI research and care in the "Big Data" era. This manuscript addresses the core elements of AKI risk prediction and outlines potential pathways and processes. We describe AKI prediction targets, feature selection, model development, and data display.

  14. Factors Associated with the Use of Preventive Care for Contrast-Induced Acute Kidney Injury

    PubMed Central

    Mor, Maria K.; Kim, Sunghee; Hartwig, Kathryn C.; Sonel, Ali F.; Palevsky, Paul M.; Fine, Michael J.

    2009-01-01

    BACKGROUND The factors that affect the implementation of preventive care for contrast-induced acute kidney injury (CIAKI) are unknown. OBJECTIVE To assess patient and provider factors associated with the use of preventive care for CIAKI. DESIGN Prospective cohort study. PARTICIPANTS Patients with kidney disease undergoing procedures with intravascular iodinated radiocontrast. MEASUREMENTS We recorded the use of preventive care defined as the administration of: (1) pre- and post-procedure isotonic intravenous (IV) fluid, (2) N-acetylcysteine, and (3) iso-osmolal radiocontrast. We surveyed patients’ providers to assess their knowledge, experience, and training on CIAKI and used multiple logistic regression to assess the independent associations of patient and provider factors with the use of these preventive interventions. RESULTS We enrolled 660 patients and 87 providers. Patient factors associated with use of IV fluid and N-acetylcysteine were higher baseline serum creatinine (OR 1.5 and 5.0, p < 0.05) and inpatient status (OR 3.0 and 6.3, p < 0.05), while higher baseline serum creatinine was associated with the use of iso-osmolal contrast (OR = 13.4, p < 0.01). The primary provider characteristics associated with the use of IV fluid and N-acetylcysteine were a greater degree of prior training on CIAKI (OR 1.9 and 2.8, p < 0.05) and higher number of prior patients with CIAKI (OR 2.7 and 2.6, p < 0.05). CONCLUSIONS Patient baseline kidney function and provider training and experience with CIAKI are independently associated with the use of preventive care. Efforts to increase and intensify the training providers receive on CIAKI may help decrease the incidence of this costly iatrogenic condition. PMID:19156472

  15. Toll‑like receptor 4 contributes to acute kidney injury after cardiopulmonary resuscitation in mice.

    PubMed

    Zhang, Qingsong; Li, Gang; Xu, Li; Li, Qian; Wang, Qianyan; Zhang, Yue; Zhang, Qing; Sun, Peng

    2016-10-01

    Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild‑type (C3H/HeN) and TLR4‑mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI). The expression of TLR4, intercellular adhesion molecule‑1 (ICAM‑1), myeloperoxidase (MPO) and growth‑regulated oncogene‑β (GRO‑β) in kidney tissues was detected. The results demonstrated that the levels of Scr and BUN increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted in increased expression of TLR4, ICAM‑1, GRO‑β and MPO in a CA‑duration dependent manner. However, there was decreased expression of ICAM‑1, GRO‑β and MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were resistant to AKI as demonstrated by the minor changes in renal histology and function following CPR. In conclusion, mice suffered from AKI after successful CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its downstream signaling events that promote neutrophil infiltration via ICAM‑1 and GRO‑β may be important in mediating inflammatory responses to renal injury after CPR. PMID:27510583

  16. Toll‑like receptor 4 contributes to acute kidney injury after cardiopulmonary resuscitation in mice.

    PubMed

    Zhang, Qingsong; Li, Gang; Xu, Li; Li, Qian; Wang, Qianyan; Zhang, Yue; Zhang, Qing; Sun, Peng

    2016-10-01

    Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild‑type (C3H/HeN) and TLR4‑mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI). The expression of TLR4, intercellular adhesion molecule‑1 (ICAM‑1), myeloperoxidase (MPO) and growth‑regulated oncogene‑β (GRO‑β) in kidney tissues was detected. The results demonstrated that the levels of Scr and BUN increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted in increased expression of TLR4, ICAM‑1, GRO‑β and MPO in a CA‑duration dependent manner. However, there was decreased expression of ICAM‑1, GRO‑β and MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were resistant to AKI as demonstrated by the minor changes in renal histology and function following CPR. In conclusion, mice suffered from AKI after successful CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its downstream signaling events that promote neutrophil infiltration via ICAM‑1 and GRO‑β may be important in mediating inflammatory responses to renal injury after CPR.

  17. Toll-like receptor 4 contributes to acute kidney injury after cardiopulmonary resuscitation in mice

    PubMed Central

    Zhang, Qingsong; Li, Gang; Xu, Li; Li, Qian; Wang, Qianyan; Zhang, Yue; Zhang, Qing; Sun, Peng

    2016-01-01

    Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild-type (C3H/HeN) and TLR4-mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI). The expression of TLR4, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) and growth-regulated oncogene-β (GRO-β) in kidney tissues was detected. The results demonstrated that the levels of Scr and BUN increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted in increased expression of TLR4, ICAM-1, GRO-β and MPO in a CA-duration dependent manner. However, there was decreased expression of ICAM-1, GRO-β and MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were resistant to AKI as demonstrated by the minor changes in renal histology and function following CPR. In conclusion, mice suffered from AKI after successful CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its downstream signaling events that promote neutrophil infiltration via ICAM-1 and GRO-β may be important in mediating inflammatory responses to renal injury after CPR. PMID:27510583

  18. Impaired endothelial proliferation and mesenchymal transition contribute to vascular rarefaction following acute kidney injury.

    PubMed

    Basile, David P; Friedrich, Jessica L; Spahic, Jasmina; Knipe, Nicole; Mang, Henry; Leonard, Ellen C; Changizi-Ashtiyani, Saeed; Bacallao, Robert L; Molitoris, Bruce A; Sutton, Timothy A

    2011-03-01

    Acute kidney injury induces the loss of renal microvessels, but the fate of endothelial cells and the mechanism of potential vascular endothelial growth factor (VEGF)-mediated protection is unknown. Cumulative cell proliferation was analyzed in the kidney of Sprague-Dawley rats following ischemia-reperfusion (I/R) injury by repetitive administration of BrdU (twice daily) and colocalization in endothelial cells with CD31 or cablin. Proliferating endothelial cells were undetectable for up to 2 days following I/R and accounted for only ∼1% of BrdU-positive cells after 7 days. VEGF-121 preserved vascular loss following I/R but did not affect proliferation of endothelial, perivascular cells or tubular cells. Endothelial mesenchymal transition states were identified by localizing endothelial markers (CD31, cablin, or infused tomato lectin) with the fibroblast marker S100A4. Such structures were prominent within 6 h and sustained for at least 7 days following I/R. A Tie-2-cre transgenic crossed with a yellow fluorescent protein (YFP) reporter mouse was used to trace the fate of endothelial cells and demonstrated interstititial expansion of YFP-positive cells colocalizing with S100A4 and smooth muscle actin following I/R. The interstitial expansion of YFP cells was attenuated by VEGF-121. Multiphoton imaging of transgenic mice revealed the alteration of YFP-positive vascular cells associated with blood vessels characterized by limited perfusion in vivo. Taken together, these data indicate that vascular dropout post-AKI results from endothelial phenotypic transition combined with an impaired regenerative capacity, which may contribute to progressive chronic kidney disease. PMID:21123492

  19. Alkaline phosphatase: a possible treatment for sepsis-associated acute kidney injury in critically ill patients.

    PubMed

    Peters, Esther; Heemskerk, Suzanne; Masereeuw, Rosalinde; Pickkers, Peter

    2014-06-01

    Acute kidney injury (AKI) is a common disease in the intensive care unit and accounts for high morbidity and mortality. Sepsis, the predominant cause of AKI in this setting, involves a complex pathogenesis in which renal inflammation and hypoxia are believed to play an important role. A new therapy should be aimed at targeting both these processes, and the enzyme alkaline phosphatase, with its dual mode of action, might be a promising candidate. First, alkaline phosphatase is able to reduce inflammation through dephosphorylation and thereby detoxification of endotoxin (lipopolysaccharide), which is an important mediator of sepsis. Second, adenosine triphosphate, released during cellular stress caused by inflammation and hypoxia, has detrimental effects but can be converted by alkaline phosphatase into adenosine with anti-inflammatory and tissue-protective effects. These postulated beneficial effects of alkaline phosphatase have been confirmed in animal experiments and two phase 2a clinical trials showing that kidney function improved in critically ill patients with sepsis-associated AKI. Because renal inflammation and hypoxia also are observed commonly in AKI induced by other causes, it would be of interest to investigate the therapeutic effect of alkaline phosphatase in these nephropathies as well.

  20. Septic acute kidney injury: molecular mechanisms and the importance of stratification and targeting therapy.

    PubMed

    Morrell, Eric D; Kellum, John A; Pastor-Soler, Núria M; Hallows, Kenneth R

    2014-01-01

    The most common cause of acute kidney injury (AKI) in hospitalized patients is sepsis. However, the molecular pathways and mechanisms that mediate septic AKI are not well defined. Experiments performed over the past 20 years suggest that there are profound differences in the pathogenesis between septic and ischemic AKI. Septic AKI often occurs independently of hypoperfusion, and is mediated by a concomitant pro- and anti-inflammatory state that is activated in response to various pathogen-associated molecular patterns, such as endotoxin, as well as damage-associated molecular patterns. These molecular patterns are recognized by Toll-like receptors (TLRs) found in the kidney, and effectuate downstream inflammatory pathways. Additionally, apoptosis has been proposed to play a role in the pathogenesis of septic AKI. However, targeted therapies designed to mitigate the above aspects of the inflammatory state, TLR-related pathways, and apoptosis have failed to show significant clinical benefit. This failure is likely due to the protean nature of septic AKI, whereby different patients present at different points along the immunologic spectrum. While one patient may benefit from targeted therapy at one end of the spectrum, another patient at the other end may be harmed by the same therapy. We propose that a next important step in septic AKI research will be to identify where patients lie on the immunologic spectrum in order to appropriately target therapies at the inflammatory cascade, TLRs, and possibly apoptosis. PMID:25575158

  1. Acute kidney injury following cardiac surgery: current understanding and future directions.

    PubMed

    O'Neal, Jason B; Shaw, Andrew D; Billings, Frederic T

    2016-07-04

    Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI.

  2. The effect of cold ischemia time on delayed graft function and acute rejection in kidney transplantation.

    PubMed

    Sert, Ismail; Colak, Hulya; Tugmen, Cem; Dogan, Sait Murat; Karaca, Cezmi

    2014-09-01

    The objective of this study is to evaluate the impact of cold ischemia time (CIT) on delayed graft function (DGF) and acute rejection (AR) among deceased donor kidney transplant recipients. The medical records of 111 patients who underwent kidney transplantation from deceased donors between November 1994 and July 2009 were retrospectively analyzed. DGF was observed in 54% of the patients and the prevalence of AR in the first year after transplantation was 9.9%. The incidence of DGF was higher among patients with longer CIT. There was no correlation between CIT and AR episodes. Higher body weight of recipients and donors, history of prior blood transfusion and advanced donor age were related with DGF. Patients with DGF had higher serum creatinine levels at the first, third and fifth years. There was a negative correlation between recipient body weight and creatinine clearance at the first year. CIT has an important role in the development of DGF as a modifiable risk factor. Moreover, donors with advanced age and higher body weight as well as recipients with higher body weight and history of blood transfusions are at risk for the development of DGF. Prevention of DGF may help to improve graft function at the first, third and fifth years and shorten the hospital stay.

  3. The definition of acute kidney injury and its use in practice.

    PubMed

    Thomas, Mark E; Blaine, Caroline; Dawnay, Anne; Devonald, Mark A J; Ftouh, Saoussen; Laing, Chris; Latchem, Susan; Lewington, Andrew; Milford, David V; Ostermann, Marlies

    2015-01-01

    Acute kidney injury (AKI) is a common syndrome that is independently associated with increased mortality. A standardized definition is important to facilitate clinical care and research. The definition of AKI has evolved rapidly since 2004, with the introduction of the Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) classifications. RIFLE was modified for pediatric use (pRIFLE). They were developed using both evidence and consensus. Small rises in serum creatinine are independently associated with increased mortality, and hence are incorporated into the current definition of AKI. The recent definition from the international KDIGO guideline merged RIFLE and AKIN. Systematic review has found that these definitions do not differ significantly in their performance. Health-care staff caring for children or adults should use standard criteria for AKI, such as the pRIFLE or KDIGO definitions, respectively. These efforts to standardize AKI definition are a substantial advance, although areas of uncertainty remain. The new definitions have enabled the use of electronic alerts to warn clinicians of possible AKI. Novel biomarkers may further refine the definition of AKI, but their use will need to produce tangible improvements in outcomes and cost effectiveness. Further developments in AKI definitions should be informed by research into their practical application across health-care providers. This review will discuss the definition of AKI and its use in practice for clinicians and laboratory scientists.

  4. Acute kidney injury following cardiac surgery: current understanding and future directions.

    PubMed

    O'Neal, Jason B; Shaw, Andrew D; Billings, Frederic T

    2016-01-01

    Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI. PMID:27373799

  5. Clinical analysis of cause, treatment and prognosis in acute kidney injury patients.

    PubMed

    Yang, Fan; Zhang, Li; Wu, Hao; Zou, Hongbin; Du, Yujun

    2014-01-01

    Acute kidney injury (AKI) is characterized by an abrupt decline in renal function, resulting in an inability to secrete waste products and maintain electrolyte and water balance, and is associated with high risks of morbidity and mortality. This study retrospectively analyzed clinical data, treatment, and prognosis of 271 hospitalized patients (172 males and 99 females) diagnosed with AKI from December, 2008 to December, 2011. In addition, this study explored the association between the cause of AKI and prognosis, severity and treatment of AKI. The severity of AKI was classified according to the Acute Kidney Injury Network (AKIN) criteria. Renal recovery was defined as a decrease in a serum creatinine level to the normal value. Prerenal, renal, and postrenal causes accounted for 36.5% (99 patients), 46.5% (126 patients) and 17.0% (46 patients), respectively, of the incidence of AKI. Conservative, surgical, and renal replacement treatments were given to 180 (66.4%), 30 (11.1%) and 61 patients (22.5%), respectively. The overall recovery rate was 21.0%, and the mortality rate was 19.6%. Levels of Cl(-), Na(+) and carbon dioxide combining power decreased with increasing severity of AKI. Cause and treatment were significantly associated with AKI prognosis. Likewise, the severity of AKI was significantly associated with cause, treatment and prognosis. Multivariate logistic regression analysis found that respiratory injury and multiple organ dysfunction syndrome (MODS) were associated with AKI patient death. Cause, treatment and AKIN stage are associated with the prognosis of AKI. Respiratory injury and MODS are prognostic factors for death of AKI patients.

  6. Clinical analysis of cause, treatment and prognosis in acute kidney injury patients.

    PubMed

    Yang, Fan; Zhang, Li; Wu, Hao; Zou, Hongbin; Du, Yujun

    2014-01-01

    Acute kidney injury (AKI) is characterized by an abrupt decline in renal function, resulting in an inability to secrete waste products and maintain electrolyte and water balance, and is associated with high risks of morbidity and mortality. This study retrospectively analyzed clinical data, treatment, and prognosis of 271 hospitalized patients (172 males and 99 females) diagnosed with AKI from December, 2008 to December, 2011. In addition, this study explored the association between the cause of AKI and prognosis, severity and treatment of AKI. The severity of AKI was classified according to the Acute Kidney Injury Network (AKIN) criteria. Renal recovery was defined as a decrease in a serum creatinine level to the normal value. Prerenal, renal, and postrenal causes accounted for 36.5% (99 patients), 46.5% (126 patients) and 17.0% (46 patients), respectively, of the incidence of AKI. Conservative, surgical, and renal replacement treatments were given to 180 (66.4%), 30 (11.1%) and 61 patients (22.5%), respectively. The overall recovery rate was 21.0%, and the mortality rate was 19.6%. Levels of Cl(-), Na(+) and carbon dioxide combining power decreased with increasing severity of AKI. Cause and treatment were significantly associated with AKI prognosis. Likewise, the severity of AKI was significantly associated with cause, treatment and prognosis. Multivariate logistic regression analysis found that respiratory injury and multiple organ dysfunction syndrome (MODS) were associated with AKI patient death. Cause, treatment and AKIN stage are associated with the prognosis of AKI. Respiratory injury and MODS are prognostic factors for death of AKI patients. PMID:24586237

  7. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  8. α-Melanocyte Stimulating Hormone Treatment in Pigs Does Not Improve Early Graft Function in Kidney Transplants from Brain Dead Donors

    PubMed Central

    van Rijt, Willem G.; Secher, Niels; Keller, Anna K.; Møldrup, Ulla; Chynau, Yahor; Ploeg, Rutger J.; van Goor, Harry; Nørregaard, Rikke; Birn, Henrik; Frøkiaer, Jørgen; Nielsen, Søren; Leuvenink, Henri G. D.; Jespersen, Bente

    2014-01-01

    Delayed graft function and primary non-function are serious complications following transplantation of kidneys derived from deceased brain dead (DBD) donors. α-melanocyte stimulating hormone (α-MSH) is a pleiotropic neuropeptide and its renoprotective effects have been demonstrated in models of acute kidney injury. We hypothesized that α-MSH treatment of the recipient improves early graft function and reduces inflammation following DBD kidney transplantation. Eight Danish landrace pigs served as DBD donors. After four hours of brain death both kidneys were removed and stored for 18 hours at 4°C in Custodiol preservation solution. Sixteen recipients were randomized in a paired design into two treatment groups, transplanted simultaneously. α-MSH or a vehicle was administered at start of surgery, during reperfusion and two hours post-reperfusion. The recipients were observed for ten hours following reperfusion. Blood, urine and kidney tissue samples were collected during and at the end of follow-up. α-MSH treatment reduced urine flow and impaired recovery of glomerular filtration rate (GFR) compared to controls. After each dose of α-MSH, a trend towards reduced mean arterial blood pressure and increased heart rate was observed. α-MSH did not affect expression of inflammatory markers. Surprisingly, α-MSH impaired recovery of renal function in the first ten hours following DBD kidney transplantation possibly due to hemodynamic changes. Thus, in a porcine experimental model α-MSH did not reduce renal inflammation and did not improve short-term graft function following DBD kidney transplantation. PMID:24728087

  9. Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

    PubMed Central

    Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

    2016-01-01

    Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients

  10. Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

    PubMed Central

    Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

    2016-01-01

    Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients

  11. Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery

    PubMed Central

    Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A.; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2016-01-01

    Abstract Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a

  12. Early vs. late refeeding in acute infantile diarrhea.

    PubMed

    Gazala, E; Weitzman, S; Weizman, Z; Gross, J; Bearman, J E; Gorodischer, R

    1988-03-01

    A randomized ambulatory trial was performed to compare early (6-h) vs. late (24-h) refeeding in acute infantile diarrhea. Ninety infants with mild dehydration were enrolled in the study. Following an initial oral rehydration period (WHO formula), refeeding was introduced using a diet based on either breast milk or cow's milk. Early (n = 53) and late (n = 37) refeeding groups were similar in ethnic background, socioeconomic level, relevant past history, nutritional and clinical state, and stool pathogens. Infants were assessed upon their initial visit, at 24 and 48 h, and at 7 and 14 days thereafter for evaluation of weight, hydration state, stool frequency and need of hospitalization. No significant differences in the above parameters were observed between the two groups. Different patterns of refeeding (breast milk vs. cow's milk) in both early and late refeeding groups showed no significant differences in the features studied. Since the short-term clinical outcome following early refeeding in acute infantile diarrhea is not different from late refeeding, we suggest that early refeeding should be preferred, particularly in developing populations, in order to minimize the adverse nutritional effects of prolonged fasting during recurrent bouts of gastroenteritis. PMID:3286579

  13. Early Hospital Readmission After Simultaneous Pancreas-Kidney Transplantation: Patient and Center-Level Factors.

    PubMed

    King, E A; Kucirka, L M; McAdams-DeMarco, M A; Massie, A B; Al Ammary, F; Ahmed, R; Grams, M E; Segev, D L

    2016-02-01

    Early hospital readmission is associated with increased morbidity, mortality, and cost. Following simultaneous pancreas-kidney transplantation, rates of readmission and risk factors for readmission are unknown. We used United States Renal Data System data to study 3643 adult primary first-time simultaneous pancreas-kidney recipients from December 1, 1999 to October 31, 2011. Early hospital readmission was any hospitalization within 30 days of discharge. Modified Poisson regression was used to determine the association between readmission and patient-level factors. Empirical Bayes statistics were used to determine the variation attributable to center-level factors. The incidence of readmission was 55.5%. Each decade increase in age was associated with an 11% lower risk of readmission to age 40, beyond which there was no association. Donor African-American race was associated with a 13% higher risk of readmission. Each day increase in length of stay was associated with a 2% higher risk of readmission until 14 days, beyond which each day increase was associated with a 1% reduction in the risk of readmission. Center-level factors were not associated with readmission. The high incidence of early hospital readmission following simultaneous pancreas-kidney transplant may reflect clinical complexity rather than poor quality of care.

  14. Comparison of Acute Kidney Injury After Robot-Assisted Laparoscopic Radical Prostatectomy Versus Retropubic Radical Prostatectomy

    PubMed Central

    Joo, Eun-Young; Moon, Yeon-Jin; Yoon, Syn-Hae; Chin, Ji-Hyun; Hwang, Jai-Hyun; Kim, Young-Kug

    2016-01-01

    Abstract Acute kidney injury (AKI) is associated with extended hospital stay, a high risk of progressive chronic kidney diseases, and increased mortality. Patients undergoing radical prostatectomy are at increased risk of AKI because of intraoperative bleeding, obstructive uropathy, older age, and preexisting chronic kidney disease. In particular, robot-assisted laparoscopic radical prostatectomy (RALP), which is in increasing demand as an alternative surgical option for retropubic radical prostatectomy (RRP), is associated with postoperative renal dysfunction because pneumoperitoneum during RALP can decrease cardiac output and renal perfusion. The objective of this study was to compare the incidence of postoperative AKI between RRP and RALP. We included 1340 patients who underwent RRP (n = 370) or RALP (n = 970) between 2013 and 2014. Demographics, cancer-related data, and perioperative laboratory data were evaluated. Postoperative AKI was determined according to the Kidney Disease: Improving Global Outcomes criteria. Operation and anesthesia time, estimated blood loss, amounts of administered fluids and transfused packed red blood cells, and the lengths of the postoperative intensive care unit and hospital stays were evaluated. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences between the RRP and RALP groups. After performing 1:1 propensity score matching, the RRP and RALP groups included 307 patients, respectively. The operation time and anesthesia time in RALP were significantly longer than in the RRP group (both P < 0.001). However, the estimated blood loss and amount of administered fluids in RALP were significantly lower than in RRP (both P < 0.001). Also, RALP demonstrated a significantly lower incidence of transfusion and smaller amount of transfused packed red blood cells than RRP (both P < 0.001). Importantly, the incidence of AKI in RALP

  15. Outcomes After Kidney injury in Surgery (OAKS): protocol for a multicentre, observational cohort study of acute kidney injury following major gastrointestinal and liver surgery

    PubMed Central

    2016-01-01

    Introduction Acute kidney injury (AKI) is associated with increased morbidity and mortality following cardiac surgery. Data focusing on the patterns of AKI following major gastrointestinal surgery could inform quality improvement projects and clinical trials, but there is a lack of reliable evidence. This multicentre study aims to determine the incidence and impact of AKI following major gastrointestinal and liver surgery. Methods and analysis This prospective, collaborative, multicentre cohort study will include consecutive adults undergoing gastrointestinal resection, liver resection or reversal of ileostomy or colostomy. Open and laparoscopic procedures in elective and emergency patients will be included in the study. The primary end point will be the incidence of AKI within 7 days of surgery, identified using an adaptation of the National Algorithm for Detecting Acute Kidney Injury, which is based on the Kidney Disease Improving Global Outcomes (KDIGO) AKI guidelines. Secondary outcomes will include persistent renal dysfunction at discharge and 1 year postoperatively. The 30-day adverse event rate will be measured using the Clavien-Dindo scale. Data on factors that may predispose to the development of AKI will be collected to identify variables associated with AKI. Based on our previous collaborative studies, a minimum of 114 centres are expected to be recruited, contributing over 6500 patients in total. Ethics and dissemination This study will be registered as clinical audit at each participating hospital. The protocol will be disseminated through local and national medical student networks in the UK and Ireland. PMID:26769786

  16. Urinary Kininogen-1 and Retinol binding protein-4 respond to Acute Kidney Injury: predictors of patient prognosis?

    PubMed Central

    Gonzalez-Calero, Laura; Martin-Lorenzo, Marta; Ramos-Barron, Angeles; Ruiz-Criado, Jorge; Maroto, Aroa S.; Ortiz, Alberto; Gomez-Alamillo, Carlos; Arias, Manuel; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2016-01-01

    Implementation of therapy for acute kidney injury (AKI) depends on successful prediction of individual patient prognosis. Clinical markers as serum creatinine (sCr) have limitations in sensitivity and early response. The aim of the study was to identify novel molecules in urine which show altered levels in response to AKI and investigate their value as predictors of recovery. Changes in the urinary proteome were here investigated in a cohort of 88 subjects (55 AKI patients and 33 healthy donors) grouped in discovery and validation independent cohorts. Patients’ urine was collected at three time points: within the first 48 h after diagnosis(T1), at 7 days of follow-up(T2) and at discharge of Nephrology(T3). Differential gel electrophoresis was performed and data were confirmed by Western blot (WB), liquid chromatography/mass spectrometry (LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). Retinol binding protein 4 (RBP4) and kininogen-1 (KNG1) were found significantly altered following AKI. RBP4 increased at T1, and progressively decreased towards normalization. Maintained decrease was observed for KNG1 from T1. Individual patient response along time revealed RBP4 responds to recovery earlier than sCr. In conclusion, KNG1 and RBP4 respond to AKI. By monitoring RBP4, patient’s recovery can be anticipated pointing to a role of RBP4 in prognosis evaluation. PMID:26792617

  17. Acute kidney injury: short-term and long-term effects.

    PubMed

    Doyle, James F; Forni, Lui G

    2016-01-01

    Acute kidney injury (AKI) is the most common cause of organ dysfunction in critically ill adults, with a single episode of AKI, regardless of stage, carrying a significant morbidity and mortality risk. Since the consensus on AKI nomenclature has been reached, data reflecting outcomes have become more apparent allowing investigation of both short- and long-term outcomes.Classically the short-term effects of AKI can be thought of as those reflecting an acute deterioration in renal function per se. However, the effects of AKI, especially with regard to distant organ function ("organ cross-talk"), are being elucidated as is the increased susceptibility to other conditions. With regards to the long-term effects, the consideration that outcome is a simple binary endpoint of dialysis or not, or survival or not, is overly simplistic, with the reality being much more complex.Also discussed are currently available treatment strategies to mitigate these adverse effects, as they have the potential to improve patient outcome and provide considerable economic health savings. Moving forward, an agreement for defining renal recovery is warranted if we are to assess and extrapolate the efficacy of novel therapies. Future research should focus on targeted therapies assessed by measure of long-term outcomes. PMID:27373891

  18. Maternal, fetal and renal outcomes of pregnancy-associated acute kidney injury requiring dialysis.

    PubMed

    Krishna, A; Singh, R; Prasad, N; Gupta, A; Bhadauria, D; Kaul, A; Sharma, R K; Kapoor, D

    2015-01-01

    Pregnancy-associated acute kidney injury (PAKI) is encountered frequently in developing countries. We evaluated the maternal, fetal and renal outcomes in women with PAKI who needed at least one session of dialysis. Of the total of 98 cases (mean age 28.85 ± 5.13 years; mean parity 2.65 ± 1.28) of PAKI, the most common cause of PAKI was postabortal sepsis. Eighteen patients died; those with oligoanuria, sepsis and central nervous system (CNS) involvement were at greater risk of mortality. The relative risk (RR) of neonatal mortality was lower after with full-term delivery (RR: 0.17, 95% confidence interval (CI): 0.03-0.96, P = 0.02) compared to preterm delivery. Of the 80 surviving patients, 60 (75%) patients achieved complete recovery of renal function at the end of 3 months; and of the remaining 14 had presumed (n = 4) or, biopsy-proven (n = 10) acute patchy cortical necrosis. The RR of non-recovery of renal function was high (RR: 24.7, 95% CI: 3.4- 179.5) in patients who did not recover at 6 weeks. Of the 14 patients with cortical necrosis, 3 (21.42%) became independent of dialysis at 6 months. PAKI patients should be watched for dialysis independency for 6 months. PMID:25838643

  19. Acute effects of grayanotoxin in rhododendron honey on kidney functions in rats.

    PubMed

    Silici, S; Doğan, Z; Sahin, H; Atayoğlu, T; Yakan, B

    2016-02-01

    The aim of the study is to evaluate the acute biochemical and histological changes in rat kidneys after treatment with grayanotoxin (GTX) of rhododendron honey (RH). A total of 60 Sprague-Dawley female rats were divided into five groups of 12 rats each, one being a control group (group 1) and group 2 was treated with 0.015 mg/kg/bw of GTX standard preparation via intraperitoneal injection. Groups 3, 4, and 5 were given RH at doses of 0.1, 0.5, and 2.5 g/kg/bw, respectively, via oral gavage. Compared to the control group, significant increases were observed in glucose, blood urea nitrogen (BUN), and creatinine levels of the GTX-injected groups after 1 h. However, in low dose RH group, such an increase was not observed and had a normal appearance histologically. Therefore, low dose (1 g/kg/bw) of RH produces no acute adverse effects on renal functions of rats.

  20. Risk prediction of acute kidney injury in cardiac surgery and prevention using aminophylline.

    PubMed

    Mahaldar, A R; Sampathkumar, K; Raghuram, A R; Kumar, S; Ramakrishnan, M; Mahaldar, D A C

    2012-05-01

    The incidence of acute kidney injury (AKI) after cardiac surgery remains high. The nonspecific adenosine receptor antagonist aminophylline has been shown to confer benefit in experimental and clinical acute renal failure (ARF) due to ischemia, contrast media, and various nephrotoxic agents. We conducted a prospective open label trial to assess the effectiveness of aminophylline for prevention of renal impairment after cardiac surgery. One hundred and thirty-eight patients undergoing cardiac surgery were risk stratified as per Cleveland score to assess for prediction of AKI. Sixty-three patients received a bolus aminophylline of 5 mg/kg and a subsequent continuous infusion of 0.25 mg/kg/h for up to 72 h, while 75 patients received usual postoperative care. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery and the glomerular filtration rate estimated using Cockcroft and Gault formula. Hourly urine output was recorded and patients assigned to respective RIFLE stage of AKI. Cleveland score ≥6 was associated with higher incidence of AKI: I and F (P<0.005). Number needed to treat, an insight into the clinical relevance of a specific treatment, is 8. These results suggest that the perioperative use of aminophylline infusion is associated with lower incidence of deterioration in renal function following cardiac surgery in high-risk patients. PMID:23087551

  1. Risk prediction of acute kidney injury in cardiac surgery and prevention using aminophylline

    PubMed Central

    Mahaldar, A. R.; Sampathkumar, K.; Raghuram, A. R.; Kumar, S.; Ramakrishnan, M.; Mahaldar, D. A. C.

    2012-01-01

    The incidence of acute kidney injury (AKI) after cardiac surgery remains high. The nonspecific adenosine receptor antagonist aminophylline has been shown to confer benefit in experimental and clinical acute renal failure (ARF) due to ischemia, contrast media, and various nephrotoxic agents. We conducted a prospective open label trial to assess the effectiveness of aminophylline for prevention of renal impairment after cardiac surgery. One hundred and thirty-eight patients undergoing cardiac surgery were risk stratified as per Cleveland score to assess for prediction of AKI. Sixty-three patients received a bolus aminophylline of 5 mg/kg and a subsequent continuous infusion of 0.25 mg/kg/h for up to 72 h, while 75 patients received usual postoperative care. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery and the glomerular filtration rate estimated using Cockcroft and Gault formula. Hourly urine output was recorded and patients assigned to respective RIFLE stage of AKI. Cleveland score ≥6 was associated with higher incidence of AKI: I and F (P<0.005). Number needed to treat, an insight into the clinical relevance of a specific treatment, is 8. These results suggest that the perioperative use of aminophylline infusion is associated with lower incidence of deterioration in renal function following cardiac surgery in high-risk patients. PMID:23087551

  2. Acute abdomen and hemorrhagic shock caused by spontaneous rupture of renal cyst in autosomal dominant polycystic kidney disease.

    PubMed

    Yaman, İsmail; Sağlam, İsmet; Kurt, Kamile

    2013-01-01

    Autosomal dominant polycystic kidney disease is an important cause of end stage renal failure. Rarely, these patients may present with hemorrhagic shock caused by rupture of the renal cyst. The aim of this study was to report a rare case of a patient who arrived at the emergency department with autosomal dominant polycystic kidney disease presenting with acute abdominal pain and hemorrhagic shock. A 58-year-old male with chronic renal failure was admitted to the emergency department with acute abdominal pain and hemorrhagic shock. The patient was admitted to the Department of Surgery with diagnosis of acute abdomen and perirenal hematoma. Although the patient was on conservative treatment, his symptoms did not improve and the patient was operated emergently. During exploration, there was bleeding from the right polycystic kidney, which was 30×20 cm in dimension. The patient underwent nephrectomy and drainage of the hematoma, and was discharged on the fifth postoperative day without any problems. Bleeding due to rupture of a cyst in autosomal dominant polycystic kidney disease occurs rarely but it may be life threatening. Although conservative methods are often preferable in treatment, surgery can be life saving for patients in whom the clinical situation does not improve.

  3. Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease

    PubMed Central

    Seliger, Stephen L.; Zhang, Amy D.; Weir, Matthew R.; Walker, Loreen; Hsu, Van Doren; Parsa, Afshin; Diamantidis, Clarissa; Fink, Jeffrey C.

    2013-01-01

    Erythropoiesis-stimulating agents (ESAs) are effective in ameliorating anemia in chronic kidney disease (CKD). However, a recent trial in diabetic CKD patients suggested a greater stroke risk associated with full correction of anemia using ESAs. We performed a case-control study examining the association of incident ESA use with acute stroke in CKD patients, using national Veterans Affairs data. Patients with eGFR<60 cc/min/1.73m2 and outpatient hemoglobin (Hb)<12g/dL were included. Acute hospitalized stroke cases (N=2071) were identified using diagnosis codes and matched 1:5 to controls without stroke. Conditional logistic regression was used to estimate the association of ESA use with stroke, adjusting for potential confounders. After multivariate adjustment, ESA use (N=1026, 8.3%) was associated with 30% greater odds of stroke (odds ratio[OR]=1.30, 95% confidence interval[CI]: 1.06, 1.58). There was significant interaction (p=.015) between ESA use and cancer; ESA use was associated with 85% greater odds of stroke in cancer patients (95% CI: 1.26, 2.65), but not associated with stroke in patients without cancer (OR=1.07, 95% CI: 0.85, 1.35). ESA-treated patients with cancer received a median initial dose 2.5 to 4 times greater than ESA patients without cancer, but pre-ESA Hb and rate of Hb change did not differ between groups. Among a large national sample of anemic CKD patients, ESA treatment is associated with an increased risk of acute stroke, with the greatest effect among patients with cancer. PMID:21389972

  4. [Computed tomography following extracorporeal shockwave lithotripsy (ESWL) of the kidneys. I: Correlation with acute histopathological findings in experimental animals].

    PubMed

    Schaub, T; Kunisch, M; Stadtbäumer, M; Störkel, S; el-Damanhoury, H; Hennes, H J; Schild, H; Thelen, M

    1991-03-01

    In an experimental study on pigs, 28 stone-free kidneys were treated with a second generation lithotripter. Histologically, acute bleeding was seen after ESWL in 23 (82%) of the 28 treated kidneys. CT studies before and after contrast were correct in 20/28 (74%) cases. It was shown that extracorporeal shock waves cause renal bleeding that is only partially detected by computed tomography. It can be concluded that the CT findings seen in a high percentage of renal stone patients after ESWL represent bleeding. The incidence of renal bleeding after ESWL and thus the possible risk of hypertension has obviously been underestimated so far in clinical studies.

  5. Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study

    PubMed Central

    2011-01-01

    Introduction Conventional markers of acute kidney injury (AKI) lack diagnostic accuracy and are expressed only late after cardiac surgery with cardiopulmonary bypass (CPB). Recently, interest has focused on hepcidin, a regulator of iron homeostasis, as a unique renal biomarker. Methods We studied 100 adult patients in the control arm of a randomized, controlled trial http://www.clinicaltrials.gov/NCT00672334 who were identified as being at increased risk of AKI after cardiac surgery with CPB. AKI was defined according to the Risk, Injury, Failure, Loss, End-stage renal disease classification of AKI classification stage. Samples of plasma and urine were obtained simultaneously (1) before CPB (2) six hours after the start of CPB and (3) twenty-four hours after CPB. Plasma and urine hepcidin 25-isoforms were quantified by competitive enzyme-linked immunoassay. Results In AKI-free patients (N = 91), urine hepcidin concentrations had largely increased at six and twenty-four hours after CPB, and they were three to seven times higher compared to patients with subsequent AKI (N = 9) in whom postoperative urine hepcidin remained at preoperative levels (P = 0.004, P = 0.002). Furthermore, higher urine hepcidin and, even more so, urine hepcidin adjusted to urine creatinine at six hours after CPB discriminated patients who did not develop AKI (area under the curve (AUC) receiver operating characteristic curve 0.80 [95% confidence interval (95% CI) 0.71 to 0.87] and 0.88 [95% CI 0.78 to 0.97]) or did not need renal replacement therapy initiation (AUC 0.81 [95% CI 0.72 to 0.88] 0.88 [95% CI 0.70 to 0.99]) from those who did. At six hours, urine hepcidin adjusted to urine creatinine was an independent predictor of ruling out AKI (P = 0.011). Plasma hepcidin did not predict no development of AKI. The study findings remained essentially unchanged after excluding patients with preoperative chronic kidney disease. Conclusions Our findings suggest that urine hepcidin is an early

  6. The incidence and significance of acute kidney injury following emergent contrast administration in patients with STEMI and stroke.

    PubMed

    Marchick, Michael Robert; Allen, Brandon Russell; Weeks, Emily Cassin; Shuster, Jonathan Jacob; Elie, Marie-Carmelle

    2016-09-01

    The authors have investigated the incidence of acute kidney injury (AKI) and short-term mortality following an activated STEMI and stroke alert at a tertiary referral and academic center. A single center, retrospective chart review of STEMI and stroke activation patients from January 2010 to March 2012. Data was collected and reviewed from an institutional database following IRB-approval. Inclusion criteria were STEMI patients taken for cardiac catheterization, excluding patients receiving hemodialysis due to end-stage renal disease (ESRD). Primary outcome measures were the incidence of AKI using the RIFLE criteria and short-term mortality. 745 patients were included (488 stroke, 257 STEMI). The median age was 65, and 39 % were female. Overall inpatient mortality was 7.0 %. 5.4 % (40/745) of patients experienced some degree of AKI (8.6 % of STEMI, 3.7 % of stroke patients). Overall, 30 % of patients with AKI died during their hospitalization. AKI was associated with a 7.1-fold (95 % CI 3.4-15.1) increase in mortality in the entire cohort. Among STEMI patients, AKI was associated with a 66.6-fold (95 % CI 12.9-343.4) increase in mortality. These findings follow similar trends published among critically ill patients with AKI. The risk of death with concomitant AKI in this hospital population is significant and deserves future study. Early recognition and awareness in the emergency department is paramount to the patient's survival. Future studies should focus on modalities to improve early recognition and preventative therapies. PMID:26910240

  7. The incidence and significance of acute kidney injury following emergent contrast administration in patients with STEMI and stroke.

    PubMed

    Marchick, Michael Robert; Allen, Brandon Russell; Weeks, Emily Cassin; Shuster, Jonathan Jacob; Elie, Marie-Carmelle

    2016-09-01

    The authors have investigated the incidence of acute kidney injury (AKI) and short-term mortality following an activated STEMI and stroke alert at a tertiary referral and academic center. A single center, retrospective chart review of STEMI and stroke activation patients from January 2010 to March 2012. Data was collected and reviewed from an institutional database following IRB-approval. Inclusion criteria were STEMI patients taken for cardiac catheterization, excluding patients receiving hemodialysis due to end-stage renal disease (ESRD). Primary outcome measures were the incidence of AKI using the RIFLE criteria and short-term mortality. 745 patients were included (488 stroke, 257 STEMI). The median age was 65, and 39 % were female. Overall inpatient mortality was 7.0 %. 5.4 % (40/745) of patients experienced some degree of AKI (8.6 % of STEMI, 3.7 % of stroke patients). Overall, 30 % of patients with AKI died during their hospitalization. AKI was associated with a 7.1-fold (95 % CI 3.4-15.1) increase in mortality in the entire cohort. Among STEMI patients, AKI was associated with a 66.6-fold (95 % CI 12.9-343.4) increase in mortality. These findings follow similar trends published among critically ill patients with AKI. The risk of death with concomitant AKI in this hospital population is significant and deserves future study. Early recognition and awareness in the emergency department is paramount to the patient's survival. Future studies should focus on modalities to improve early recognition and preventative therapies.

  8. Renal tubular Fas ligand mediates fratricide in cisplatin-induced acute kidney failure.

    PubMed

    Linkermann, Andreas; Himmerkus, Nina; Rölver, Lars; Keyser, Kirsten A; Steen, Philip; Bräsen, Jan-Hinrich; Bleich, Markus; Kunzendorf, Ulrich; Krautwald, Stefan

    2011-01-01

    Cisplatin, a standard chemotherapeutic agent for many tumors, has an unfortunately common toxicity where almost a third of patients develop renal dysfunction after a single dose. Acute kidney injury caused by cisplatin depends on Fas-mediated apoptosis driven by Fas ligand (FasL) expressed on tubular epithelial and infiltrating immune cells. Since the role of FasL in T cells is known, we investigated whether its presence in primary kidney cells is needed for its toxic effect. We found that all cisplatin-treated wild-type (wt) mice died within 6 days; however, severe combined immunodeficiency (SCID)/beige mice (B-, T-, and natural killer-cell-deficient) displayed a significant survival benefit, with only 55% mortality while exhibiting significant renal failure. Treating SCID/beige mice with MFL3, a FasL-blocking monoclonal antibody, completely restored survival after an otherwise lethal cisplatin dose, suggesting another source of FasL besides immune cells. Freshly isolated primary tubule segments from wt mice were co-incubated with thick ascending limb (TAL) segments freshly isolated from mice expressing the green fluorescent protein (GFP) transgene (same genetic background) to determine whether FasL-mediated killing of tubular cells is an autocrine or paracrine mechanism. Cisplatin-stimulated primary segments induced apoptosis in the GFP-tagged TAL cells, an effect blocked by MFL3. Thus, our study shows that cisplatin-induced nephropathy is mediated through FasL, functionally expressed on tubular cells that are capable of inducing death of cells of adjacent tubules. PMID:20811331

  9. Acute Kidney Injury Classified by Serum Creatinine and Urine Output in Critically Ill Cancer Patients

    PubMed Central

    Herrera-Gómez, Ángel

    2016-01-01

    Acute kidney injury (AKI) is common in critically ill patients and is associated with higher mortality. Cancer patients are at an increased risk of AKI. Our objective was to determine the incidence of AKI in our critically ill cancer patients, using the criteria of serum creatinine (SCr) and urine output (UO) proposed by the Kidney Disease: Improving Global Outcomes (KDIGO). Methods. We performed a retrospective cohort analysis of a prospectively collected database at the intensive care unit (ICU) of the Instituto Nacional de Cancerología from January 2013 to March 2015. Results. We classified AKI according to the KDIGO definition. We included 389 patients; using the SCr criterion, 192 (49.4%) had AKI; using the UO criterion, 219 (56.3%) had AKI. Using both criteria, we diagnosed AKI in 69.4% of patients. All stages were independently associated with six-month mortality; stage 1 HR was 2.04 (95% CI 1.14–3.68, p = 0.017), stage 2 HR was 2.73 (95% CI 1.53–4.88, p = 0.001), and stage 3 HR was 4.5 (95% CI 2.25–8.02, p < 0.001). Patients who fulfilled both criteria had a higher mortality compared with patients who fulfilled just one criterion (HR 3.56, 95% CI 2.03–6.24, p < 0.001). Conclusion. We diagnosed AKI in 69.4% of patients. All AKI stages were associated with higher risk of death at six months, even for patients who fulfilled just one AKI criterion. PMID:27803928

  10. National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury

    PubMed Central

    Cronin, Robert M; VanHouten, Jacob P; Siew, Edward D; Eden, Svetlana K; Fihn, Stephan D; Nielson, Christopher D; Peterson, Josh F; Baker, Clifton R; Ikizler, T Alp; Speroff, Theodore

    2015-01-01

    Objective Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention. Materials and Methods A national retrospective cohort of 1,620,898 patient hospitalizations from 116 Veterans Affairs hospitals was assembled from electronic health record (EHR) data collected from 2003 to 2012. HA-AKI was defined at stage 1+, stage 2+, and dialysis. EHR-based predictors were identified through logistic regression, least absolute shrinkage and selection operator (lasso) regression, and random forests, and pair-wise comparisons between each were made. Calibration and discrimination metrics were calculated using 50 bootstrap iterations. In the final models, we report odds ratios, 95% confidence intervals, and importance rankings for predictor variables to evaluate their significance. Results The area under the receiver operating characteristic curve (AUC) for the different model outcomes ranged from 0.746 to 0.758 in stage 1+, 0.714 to 0.720 in stage 2+, and 0.823 to 0.825 in dialysis. Logistic regression had the best AUC in stage 1+ and dialysis. Random forests had the best AUC in stage 2+ but the least favorable calibration plots. Multiple risk factors were significant in our models, including some nonsteroidal anti-inflammatory drugs, blood pressure medications, antibiotics, and intravenous fluids given during the first 48 h of admission. Conclusions This study demonstrated that, although all the models tested had good discrimination, performance characteristics varied between methods, and the random forests models did not calibrate as well as the lasso or logistic regression models. In addition, novel modifiable risk factors were explored and found to be significant. PMID:26104740

  11. Antioxidant effect of Phyllanthus emblica extract prevents contrast-induced acute kidney injury

    PubMed Central

    2014-01-01

    Background Contrast-induced acute kidney injury (CI-AKI) occurs after the administration of intravenous iodinated contrast agents. Oxidative stress has been proposed as one of the most important mechanisms in the pathogenesis of CI-AKI. The objective of this study was to investigate the antioxidant effect of the extract from Phyllanthus emblica (PE) in preventing CI-AKI. Methods Male Sprague Dawley rats were subjected into eight groups, were given water (control) or PE extract (125 or 250 or 500 mg/kg/day) for 5 days before the induction of CI-AKI. Renal function and oxidative stress markers; malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activity were determined in plasma and renal tissue. Kidney sections were performed for histopathological examination. Results In the contrast media (CM) group, increases in blood urea nitrogen and serum creatinine were demonstrated which correlated with severity of tubular necrosis, peritubular capillary congestion and interstitial edema. Moreover, an increase in MDA and a decrease in TAC SOD and CAT activity in CM group were significantly changed when compared with the control (P < 0.05). In contrast, CI-AKI-induced rats administrated with PE extract 250 and 500 mg/kg/day significantly preserved renal function and attenuated the severity of pathological damage (P < 0.05) as well as significantly lower MDA and higher TAC, SOD and CAT than the CM group (P < 0.05). Conclusions This study demonstrated the protective role of PE extract against CI-AKI. PMID:24755233

  12. Comparison of postoperative acute kidney injury between ileal conduit and neobladder urinary diversions after radical cystectomy

    PubMed Central

    Joung, Kyoung-Woon; Kong, Yu-Gyeong; Yoon, Syn-Hae; Kim, Yeon Ju; Hwang, Jai-Hyun; Hong, Bumsik; Kim, Young-Kug

    2016-01-01

    Abstract Ileal conduit and neobladder urinary diversions are frequently performed after radical cystectomy. However, complications after radical cystectomy may be different according to the type of urinary diversion. Acute kidney injury (AKI) is a common complication after surgery and increases costs, morbidity, and mortality of hospitalized patients. This study was performed to compare the incidence of postoperative AKI between ileal conduit and neobladder urinary diversions after radical cystectomy. All consecutive patients who underwent radical cystectomy in 2004 to 2014 in a single tertiary care center were identified. The patients were divided into the ileal conduit and ileal neobladder groups. Preoperative variables, including demographics, cancer-related data and laboratory values, as well as intraoperative data and postoperative outcomes, including AKI, intensive care unit admission rate, and the duration of hospital stay, were evaluated between the groups. Postoperative AKI was defined according to the Kidney Disease: Improving Global Outcome criteria. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences. After performing 1:1 propensity score matching, the ileal conduit and ileal neobladder groups each included 101 patients. The overall incidence of AKI after radical cystectomy was 30.7% (62 out of 202) and the incidences did not significantly differ between the groups (27 [26.7%], ileal conduit group vs 35 [34.7%], ileal neobladder group, P = 0.268). Intraoperative data, intensive care unit admission rate, and the duration of hospital stay were not significantly different between the groups. Postoperative AKI did not significantly differ between ileal conduit and neobladder urinary diversions after radical cystectomy. This finding provides additional information useful for appropriate selection of the urinary diversion type in conjunction with radical cystectomy

  13. Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats

    PubMed Central

    YANG, SHI-KUN; DUAN, SHAO-BIN; PAN, PENG; XU, XIANG-QING; LIU, NA; XU, JUN

    2015-01-01

    Oxidative stress is an important mechanism of contrast-induced acute kidney injury (CIAKI). The optimal strategy to prevent CIAKI remains unclear. The aim of the present study was to assess the effect of pentoxifylline, a nonspecific phosphodiesterase inhibitor, on the prevention of CIAKI. A total of 32 healthy male Sprague-Dawley rats were randomly divided into normal dietary group (NN; n=8) and a high cholesterol-supplemented dietary group (HN; 4% cholesterol and 1% cholic acid; n=24). At the end of eight weeks, the rats in the high cholesterol diet group were randomly divided into three subgroups (n=8 in each group). CIAKI was induced in two of the subgroups via intravenous injection of the radiocontrast media iohexol (10 ml/kg). Pentoxifylline (50 mg/kg) was administered to one of the iohexol-treated groups via intraperitoneal injection 12 h prior to and following contrast media (CM) injection. Kidney function parameters and oxidative stress markers were then measured. The renal pathological changes were evaluated using hematoxylin and eosin staining and scored semi-quantitatively. In iohexol-injected rats, serum creatinine (Scr), renal pathological scores, renal malondialdehyde (MDA) content, renal NADPH oxidase activity, fractional excretion of sodium (FENa%) and fractional excretion of potassium (FEK%) were significantly increased (P<0.01). The Scr, histologic scores, renal MDA content, NADPH oxidase activity, FENa% and FEK% in the rats treated with pentoxifylline prior to iohexol were observed to be reduced compared with those in rats treated with iohexol alone (P<0.01). This suggests that pentoxifylline significantly attenuates renal injuries, including tubular necrosis and proteinaceous casts induced by CM. It may be concluded that pentoxifylline protected the renal tissue from the nephrotoxicity induced by low-osmolar CM via an antioxidant effect. PMID:25574202

  14. Nonapnea Sleep Disorders and the Risk of Acute Kidney Injury: A Nationwide Population-Based Study.

    PubMed

    Lin, Hugo You-Hsien; Chang, Kai-Ting; Chang, Yu-Han; Lu, Tzongshi; Liang, Chan-Jung; Wang, Dean-Chuan; Tsai, Jui-Hsiu; Hsu, Chung-Yao; Hung, Chi-Chih; Kuo, Mei-Chuan; Lin, Chang-Shen; Hwang, Shang-Jyh

    2016-03-01

    Nonapnea sleep disorders (NASDs) and associated problems, which are highly prevalent in patients with kidney diseases, are associated with unfavorable medical sequelae. Nonetheless, whether NASDs are associated with acute kidney injury (AKI) development has not been thoroughly analyzed. We examined the association between NASD and AKI. We conducted a population-based study by using 1,000,000 representative data from the Taiwan National Health Insurance Research Database for the period from January 1, 2000, to December 31, 2010. We studied the incidence and risk of AKI in 9178 newly diagnosed NASD patients compared with 27,534 people without NASD matched according to age, sex, index year, urbanization level, region of residence, and monthly income at a 1:3 ratio. The NASD cohort had an adjusted hazard ratio (hazard ratio [HR]; 95% confidence interval [CI] = 1.15-2.63) of subsequent AKI 1.74-fold higher than that of the control cohort. Older age and type 2 diabetes mellitus were significantly associated with an increased risk of AKI (P < 0.05). Among different types of NASDs, patients with insomnia had a 120% increased risk of developing AKI (95% CI = 1.38-3.51; P = 0.001), whereas patients with other sleep disorders had a 127% increased risk of subsequent AKI (95% CI = 1.07-4.80; P = 0.033). Men with NASDs were at a high risk of AKI (P < 0.05). This nationwide population-based cohort study provides evidence that patients with NASDs are at higher risk of developing AKI than people without NASDs. PMID:26986132

  15. Split liver transplant recipients do not have an increased frequency of acute kidney injury.

    PubMed

    Leithead, Joanna A; Armstrong, Matthew J; Corbett, Christopher; Andrew, Mark; Kothari, Chirag; Gunson, Bridget K; Mirza, Darius; Muiesan, Paolo; Ferguson, James W

    2014-11-01

    Small series have suggested that split liver transplantation (SLT) has an increased frequency of peri-operative acute kidney injury (AKI). However, the optimal donor selection in this setting could have a favourable impact on renal outcomes. This was a retrospective single-centre study of 76 adults who underwent SLT (right extended lobe) and 301 adults who underwent elective full-size donation after brain death liver transplantation (FSLT). SLT recipients were less likely than unmatched FSLT recipients to develop AKI (≥stage 1 KDIGO criteria) (40.3% vs. 56.1%, P = 0.016) and had a reduced frequency of renal replacement therapy (11.8% vs. 21.9%, P = 0.049). In 72 pairs of SLT patients and propensity risk score-matched FSLT controls the incidence of AKI was not significantly different (40.3% vs. 47.2%, P = 0.473). However, SLT patients were less likely to require renal replacement therapy (11.1% vs. 23.6%, P = 0.078; adjusted OR 0.32; 95% CI 0.11-0.87, P = 0.026). There was no association between SLT and the development of chronic kidney disease (eGFR<60 ml/min/1.73 m(2) , log rank P = 0.534). In conclusion, SLT is not associated with an increased frequency of AKI. These observations support the postulation that the optimal donor status of SLT may result in less graft injury with renal sparing effects. PMID:24964222

  16. Hundred top-cited articles focusing on acute kidney injury: a bibliometric analysis

    PubMed Central

    Liu, Yuan-hui; Wang, Sheng-qi; Xue, Jin-hua; Liu, Yong; Chen, Ji-yan; Li, Guo-feng; He, Peng-cheng; Tan, Ning

    2016-01-01

    Background Acute kidney injury (AKI) is a major global health issue, associated with poor short-term and long-term outcomes. Research on AKI is increasing with numerous articles published. However, the quantity and quality of research production in the field of AKI is unclear. Methods and analysis To analyse the characteristics of the most cited articles on AKI and to provide information about achievements and developments in AKI, we searched the Science Citation Index Expanded for citations of AKI articles. For the top 100 most frequently cited articles (T100), we evaluated the number of citations, publication time, province of origin, journal, impact factor, topic or subspecialty of the research, and publication type. Results The T100 articles ranged from a maximum of 1971 citations to a minimum of 215 citations (median 302 citations). T100 articles were published from 1951 to 2011, with most articles published in the 2000s (n=77), especially the 5-year period from 2002 to 2006 (n=51). The publications appeared in 30 journals, predominantly in the general medical journals, led by New England Journal of Medicine (n=17), followed by expert medical journals, led by the Journal of the American Society of Nephrology (n=16) and Kidney International (n=16). The majority (83.7%) of T100 articles were published by teams involving ≥3 authors. T100 articles originated from 15 countries, led by the USA (n=81) followed by Italy (n=9). Among the T100 articles, 69 were clinical research, 25 were basic science, 21 were reviews, 5 were meta-analyses and 3 were clinical guidelines. Most clinical articles (55%) included patients with any cause of AKI, followed by the specific causes of contrast-induced AKI (25%) and cardiac surgery-induced AKI (15%). Conclusions This study provides a historical perspective on the scientific progress on AKI, and highlights areas of research requiring further investigations and developments. PMID:27466238

  17. Gene Expression Analysis Reveals the Cell Cycle and Kinetochore Genes Participating in Ischemia Reperfusion Injury and Early Development in Kidney

    PubMed Central

    Barrera-Chimal, Jonatan; Bobadilla, Norma A.; Park, Peter J.; Vaidya, Vishal S.

    2011-01-01

    Background The molecular mechanisms that mediate the ischemia-reperfusion (I/R) injury in kidney are not completely understood. It is also largely unknown whether such mechanisms overlap with those governing the early development of kidney. Methodology/Principal Findings We performed gene expression analysis to investigate the transcriptome changes during regeneration after I/R injury in the rat (0 hr, 6 hr, 24 hr, and 120 hr after reperfusion) and early development of mouse kidney (embryonic day 16 p.c. and postnatal 1 and 7 day). Pathway analysis revealed a wide spectrum of molecular functions that may participate in the regeneration and developmental processes of kidney as well as the functional association between them. While the genes associated with cell cycle, immunity, inflammation, and apoptosis were globally activated during the regeneration after I/R injury, the genes encoding various transporters and metabolic enzymes were down-regulated. We also observed that these injury-associated molecular functions largely overlap with those of early kidney development. In particular, the up-regulation of kinases and kinesins with roles in cell division was common during regeneration and early developmental kidney as validated by real-time PCR and immunohistochemistry. Conclusions In addition to the candidate genes whose up-regulation constitutes an overlapping expression signature between kidney regeneration and development, this study lays a foundation for studying the functional relationship between two biological processes. PMID:21980527

  18. Kidney function decline after a non-dialysis-requiring acute kidney injury is associated with higher long-term mortality in critically ill survivors

    PubMed Central

    2012-01-01

    Introduction The adverse consequences of a non-dialysis-requiring acute kidney injury (AKI) are unclear. This study aimed to assess the long-term prognoses for critically ill patients experiencing a non-dialysis-requiring AKI. Methods This retrospective observational cohort study investigated non-dialysis-requiring AKI survivors in surgical intensive care units between January 2002 and June 2010. All longitudinal post-discharge serum creatinine measurements and information regarding end-stage renal disease (ESRD) and death were collected. We assessed the long-term outcomes of chronic kidney disease (CKD), ESRD and all-cause mortality beyond discharge. Results Of the 922 identified critically ill patients with a non-dialysis-requiring AKI, 634 (68.8%) patients who survived to discharge were enrolled. A total of 207 patients died after a median follow-up of 700.5 days. The median intervals between the onset of the AKI and the composite endpoints "stage 3 CKD or death", "stage 4 CKD or death", "stage 5 CKD or death", and "ESRD or death" were 685, 1319, 1743, and 2048 days, respectively. This finding shows a steady long-term decline in kidney function after discharge. Using the multivariate Cox proportional hazard model, we found that every 1 mL/min/1.73 m2 decrease from baseline estimated glomerular filtration rate (eGFR) of individuals who progressed to stage 3, 4, and 5 CKD increased the risks of long-term mortality by 0.7%, 2.3%, and 4.1%, respectively (all p < 0.05). This result indicates that the mortality risk increased significantly in a graded manner as kidney function declined from the baseline eGFR to advanced stages of CKD during the follow-up period. Conclusions In critically ill patients who survive a non-dialysis-requiring AKI, there is a need for continuous monitoring and kidney function protection beyond discharge. PMID:22789111

  19. Exploring the genetic basis of early-onset chronic kidney disease.

    PubMed

    Vivante, Asaf; Hildebrandt, Friedhelm

    2016-03-01

    The primary causes of chronic kidney disease (CKD) in children differ from those of CKD in adults. In the USA the most common diagnostic groups of renal disease that manifest before the age of 25 years are congenital anomalies of the kidneys and urinary tract, steroid-resistant nephrotic syndrome, chronic glomerulonephritis and renal cystic ciliopathies, which together encompass >70% of early-onset CKD diagnoses. Findings from the past decade suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. Developments in high-throughput sequencing in the past few years has rendered identification of causative mutations in this high number of genes feasible. Use of genetic analyses in patients with early onset-CKD will provide patients and their families with a molecular genetic diagnosis, generate new insights into disease mechanisms, facilitate aetiology-based classifications of patient cohorts for clinical studies, and might have consequences for personalized approaches to the prevention and treatment of CKD. In this Review, we discuss the implications of next-generation sequencing in clinical genetic diagnostics and the discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and the therapeutic implications of these findings. PMID:26750453

  20. Postoperative blood transfusion is an independent predictor of acute kidney injury in cardiac surgery patients

    PubMed Central

    Freeland, Kristofer; Hamidian Jahromi, Alireza; Duvall, Lucas Maier; Mancini, Mary Catherine

    2015-01-01

    Background: Acute kidney injury (AKI) is a serious complication of cardiac surgery with cardiopulmonary bypass (CPB) which increases postoperative morbidity and mortality. Objectives: The study was designed to assess the incidence of AKI and associated risk factors in patients undergoing CPB ancillary to coronary artery bypass grafting (CABG), valve surgery, and combined CABG and valve surgery. Patients and Methods: This Intuitional Review Board (IRB) approved retrospective study included patients with normal preoperative kidney function (Serum creatinine [sCr] <2.0 mg/dl) who underwent cardiac surgery with CPB between 2012 and 2014. Patients were divided into 2 groups: group I: Patients with cardiac surgery associated AKI (CS-AKI) (postoperative sCr >2 mg/dl with a minimal doubling of baseline sCr) and group II: Patients with a normal postoperative kidney function. Demographic data, body mass index (BMI), co-morbidities, hematologic/biochemical profiles, preoperative ejection fraction (%EF), blood transfusion history, and operative data were compared between the groups. Mean arterial pressure (MAP) was recorded during the operation and in the postoperative period. Δ-MAP was defined as the difference between pre-CPB-MAP and the CPB-MAP. Results: 241 patients matched the inclusion criteria (CS-AKI incidence = 8.29%). Age, gender, BMI, %EF, and co-morbidities were not predictors of CS-AKI (P > 0.05). High preoperative sCr (P = 0.047), type of procedure (P = 0.04), clamp time (P = 0.003), pump time (P = 0.005) and history of blood transfusion within 14 days postsurgery (P = 0.0004) were associated with risk of CS-AKI. Pre-CPB-MAP, CPB-MAP, Δ-MAP, and ICU-MAP were not significantly different between the 2 groups. Male gender (OR: 5.53; P = 0.048), age>60 (OR: 4.54; P = 0.027) and blood transfusion after surgery (OR: 5.25; P = 0.0054) were independent predictors for postoperative AKI. Conclusions: Age, gender and blood transfusion were independent predictors of

  1. Incidence, Outcomes, and Risk Factors of Community-Acquired and Hospital-Acquired Acute Kidney Injury

    PubMed Central

    Hsu, Chien-Ning; Lee, Chien-Te; Su, Chien-Hao; Wang, Yu-Ching Lily; Chen, Hsiao-Ling; Chuang, Jiin-Haur; Tain, You-Lin

    2016-01-01

    Abstract The disease burden and outcomes of community-acquired (CA-) and hospital-acquired acute kidney injury (HA-AKI) are not well understood. The aim of the study was to investigate the incidence, outcomes, and risk factors of AKI in a large Taiwanese adult cohort. This retrospective cohort study examined 734,340 hospital admissions from a group of hospitals within an organization in Taiwan between January 1, 2010 and December 31, 2014. Patients with AKI at discharge were classified as either CA- or HA-AKI based on the RIFLE (risk, injury, failure, loss of function, end stage of kidney disease) classification criteria. Outcomes were in-hospital mortality, dialysis, recovery of renal function, and length of stay. Risks of developing AKI were determined using multivariate logistic regression based on demographic and baseline clinical characteristics and nephrotoxin use before admission. AKI occurred in 1.68% to 2% hospital discharges among adults without and with preexisting chronic kidney disease (CKD), respectively. The incidence of CA-AKI was 17.25 and HA-AKI was 8.14 per 1000 admissions. The annual rate of CA-AKI increased from 12.43 to 19.96 per 1000 people, but the change in HA-AKI was insignificant. Comparing to CA-AKI, those with HA-AKI had higher levels of in-hospital mortality (26.07% vs 51.58%), mean length of stay (21.25 ± 22.35 vs 35.84 ± 34.62 days), and dialysis during hospitalization (1.45% vs 2.06%). Preexisting systemic diseases, including CKD were associated with increased risks of CA-AKI, and nephrotoxic polypharmacy increased risk of both CA- and HA-AKI. Patients with HA-AKI had more severe outcomes than patients with CA-AKI, and demonstrated different spectrum of risk factors. Although patients with CA-AKI with better outcomes, the incidence increased over time. It is also clear that optimal preventive and management strategies of HA- and CA-AKI are urgently needed to limit the risks in susceptible individuals. PMID:27175701

  2. An initial evaluation of post-cardiopulmonary bypass acute kidney injury in swine☆

    PubMed Central

    Murphy, Gavin J.; Lin, Hua; Coward, Richard J.; Toth, Tibor; Holmes, Robin; Hall, David; Angelini, Gianni D.

    2016-01-01

    Objective Acute kidney injury (AKI) post-cardiac surgery is associated with mortality rates approaching 20%. The development of effective treatments is hindered by the poor homology between rodent models, the mainstay of research into AKI, and that which occurs in humans. This pilot study aims to characterise post-cardiopulmonary bypass (CPB) AKI in an animal model with potentially greater homology to cardiac surgery patients. Methods and results Adult pigs, weighing 50–75 kg, underwent 2.5 h of CPB. Pigs undergoing saphenous vein grafting procedures served as controls. Pre-CPB measures of porcine renal function were within normal ranges for adult humans. The effect of CPB on renal function; a 25% reduction in 51Cr-EDTA clearance ( p = 0.068), and a 33% reduction in creatinine clearance (p = 0.043), was similar to those reported in clinical studies. CPB resulted in tubular epithelial injury (median NAG/creatinine ratio 2.6 u mmol−1 (interquartile range (IQR): 0.81–5.43) post-CPB vs 0.48 u mmol−1 (IQR: 0.37–0.97) pre-CPB, p = 0.043) as well as glomerular and/or proximal tubular injury (median albumin/creatinine ratio 6.8 mg mmol−1 (IQR: 5.45–13.06) post-CPB vs 1.10 mg mmol−1 (IQR: 0.05–2.00) pre-CPB, p = 0.080). Tubular injury scores were significantly higher in kidneys post-CPB (median score 2.0 (IQR: 1.0–2.0) relative to vein graft controls (median score 1.0 (IQR 1.0–1.0), p = 0.019). AKI was associated with endothelial injury and activation, as demonstrated by reduced DBA (dolichos biflorus agglutinin) lectin and increased endothelin-1 and vascular cell adhesion molecule (VCAM) staining. Conclusions The porcine model of post-CPB AKI shows significant homology to AKI in cardiac surgical patients. It links functional, urinary and histological measures of kidney injury and may offer novel insights into the mechanisms underlying post-CPB AKI. PMID:19692256

  3. Potential use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference.

    PubMed

    Murray, Patrick T; Mehta, Ravindra L; Shaw, Andrew; Ronco, Claudio; Endre, Zoltan; Kellum, John A; Chawla, Lakhmir S; Cruz, Dinna; Ince, Can; Okusa, Mark D

    2014-03-01

    Over the last decade there has been considerable progress in the discovery and development of biomarkers of kidney disease, and several have now been evaluated in different clinical settings. Although there is a growing literature on the performance of various biomarkers in clinical studies, there is limited information on how these biomarkers would be utilized by clinicians to manage patients with acute kidney injury (AKI). Recognizing this gap in knowledge, we convened the 10th Acute Dialysis Quality Initiative meeting to review the literature on biomarkers in AKI and their application in clinical practice. We asked an international group of experts to assess four broad areas for biomarker utilization for AKI: risk assessment, diagnosis, and staging; differential diagnosis; prognosis and management; and novel physiological techniques including imaging. This article provides a summary of the key findings and recommendations of the group, to equip clinicians to effectively use biomarkers in AKI.

  4. Increased Risk of Active Tuberculosis following Acute Kidney Injury: A Nationwide, Population-Based Study

    PubMed Central

    Chang, Chia-Hsui; Huang, Hui-Yu; Huang, Tao-Min; Lai, Chun-Fu; Lin, Meng-Chun; Ko, Wen-Je; Wu, Kwan-Dun; Yu, Chong-Jen; Shu, Chin-Chung; Lee, Chih-Hsin; Wang, Jann-Yuan

    2013-01-01

    Background Profound alterations in immune responses associated with uremia and exacerbated by dialysis increase the risk of active tuberculosis (TB). Evidence of the long-term risk and outcome of active TB after acute kidney injury (AKI) is limited. Methods This population-based-cohort study used claim records retrieved from the Taiwan National Health Insurance database. We retrieved records of all hospitalized patients, more than 18 years, who underwent dialysis for acute kidney injury (AKI) during 1999–2008 and validated using the NSARF data. Time-dependent Cox proportional hazards model to adjust for the ongoing effect of end-stage renal disease (ESRD) was conducted to predict long-term de novo active TB after discharge from index hospitalization. Results Out of 2,909 AKI dialysis patients surviving 90 days after index discharge, 686 did not require dialysis after hospital discharge. The control group included 11,636 hospital patients without AKI, dialysis, or history of TB. The relative risk of active TB in AKI dialysis patients, relative to the general population, after a mean follow-up period of 3.6 years was 7.71. Patients who did (hazard ratio [HR], 3.84; p<0.001) and did not (HR, 6.39; p<0.001) recover from AKI requiring dialysis had significantly higher incidence of TB than patients without AKI. The external validated data also showed nonrecovery subgroup (HR = 4.37; p = 0.049) had high risk of developing active TB compared with non-AKI. Additionally, active TB was associated with long-term all-cause mortality after AKI requiring dialysis (HR, 1.34; p = 0.032). Conclusions AKI requiring dialysis seems to independently increase the long-term risk of active TB, even among those who weaned from dialysis at discharge. These results raise concerns that the increasing global burden of AKI will in turn increase the incidence of active TB. PMID:23936044

  5. Protective effect of penehyclidine hydrochloride on lipopolysaccharide-induced acute kidney injury in rat.

    PubMed

    Cao, H J; Yu, D M; Zhang, T Z; Zhou, J; Chen, K Y; Ge, J; Pei, L

    2015-08-10

    We aimed to observe the effect of penehyclidine hydrochloride (PHC) on lipopolysaccharide (LPS)-induced acute kidney injury in rats and expression of tight junction proteins ZO-1 and occludin. Adult male Sprague-Dawley (SD) rats were divided randomly (N = 10) into control group (C), LPS group (LPS), low-dose PHC group (L-PHC), and high-dose PHC group (H-PHC). All rats, except C group, received a vena caudalis injection of 5.0 mg/kg LPS; after 30 min, rats in L-PHC and H-PHC groups received a vena caudalis injection of 0.3 and 0.9 mg/kg PHC. After 24 h, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, serum creatinine (Scr), and blood urea nitrogen (BUN) were detected. Histopathological changes and expression of ZO-1 and occludin were observed in renal tissues. Versus levels of TNF-α (38.5 ± 9.0), IL-1β (46.3 ± 12.7), Scr (37.2 ± 9.3), and BUN (6.5 ± 1.1) in control group, those in LPS group, TNF-α (159.0 ± 21.3), IL-1β (130.8 ± 18.7), Scr (98.5 ± 18.2), and BUN (12.8 ± 1.8), increased obviously (P < 0.05), with significantly structural changes and decreases of ZO-1 and occludin. However, TNF-α (111.3 ± 11.6), IL-1β (78.4 ± 14.3), Scr (51.3 ± 12.5), BUN (8.1 ± 1.2) in H-PHC group, and TNF-α (120.8 ± 14.3), IL-1β (92.5 ± 19.0), Scr (56.7 ± 14.7), BUN (9.7 ± 1.6) in L-PHC group were obviously decreased (P < 0.05). PHC has protective effects on acute kidney injury in sepsis, including abatement of renal tissue inflammation and functional improvement, potentially by upregulating ZO-1 and occludin.

  6. Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease

    PubMed Central

    Bouchard, Josée; Soroko, Sharon B.; Ikizler, T. Alp; Paganini, Emil P.; Chertow, Glenn M.; Himmelfarb, Jonathan

    2010-01-01

    Purpose Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI. Methods We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis. Results We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI. Conclusions Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis. PMID:21152901

  7. Renal progenitors derived from human iPSCs engraft and restore function in a mouse model of acute kidney injury

    PubMed Central

    Imberti, Barbara; Tomasoni, Susanna; Ciampi, Osele; Pezzotta, Anna; Derosas, Manuela; Xinaris, Christodoulos; Rizzo, Paola; Papadimou, Evangelia; Novelli, Rubina; Benigni, Ariela; Remuzzi, Giuseppe; Morigi, Marina

    2015-01-01

    Acute kidney injury (AKI) is one of the most relevant health issues, leading to millions of deaths. The magnitude of the phenomenon remarks the urgent need for innovative and effective therapeutic approaches. Cell-based therapy with renal progenitor cells (RPCs) has been proposed as a possible strategy. Studies have shown the feasibility of directing embryonic stem cells or induced Pluripotent Stem Cells (iPSCs) towards nephrogenic intermediate mesoderm and metanephric mesenchyme (MM). However, the functional activity of iPSC-derived RPCs has not been tested in animal models of kidney disease. Here, through an efficient inductive protocol, we directed human iPSCs towards RPCs that robustly engrafted into damaged tubuli and restored renal function and structure in cisplatin-mice with AKI. These results demonstrate that iPSCs are a valuable source of engraftable cells with regenerative activity for kidney disease and create the basis for future applications in stem cell-based therapy. PMID:25744951

  8. Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

    PubMed Central

    Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

    2016-01-01

    Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

  9. A Case of Mushroom Poisoning with Russula subnigricans: Development of Rhabdomyolysis, Acute Kidney Injury, Cardiogenic Shock, and Death

    PubMed Central

    2016-01-01

    Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis. PMID:27366018

  10. Prognostic impact of atrial fibrillation on clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease

    PubMed Central

    Patel, Nileshkumar J; Patel, Aashay; Agnihotri, Kanishk; Pau, Dhaval; Patel, Samir; Thakkar, Badal; Nalluri, Nikhil; Asti, Deepak; Kanotra, Ritesh; Kadavath, Sabeeda; Arora, Shilpkumar; Patel, Nilay; Patel, Achint; Sheikh, Azfar; Patel, Neil; Badheka, Apurva O; Deshmukh, Abhishek; Paydak, Hakan; Viles-Gonzalez, Juan

    2015-01-01

    Atrial fibrillation (AF) is the most common type of sustained arrhythmia, which is now on course to reach epidemic proportions in the elderly population. AF is a commonly encountered comorbidity in patients with cardiac and major non-cardiac diseases. Morbidity and mortality associated with AF makes it a major healthcare burden. The objective of our article is to determine the prognostic impact of AF on acute coronary syndromes, heart failure and chronic kidney disease. Multiple studies have been conducted to determine if AF has an independent role in the overall mortality of such patients. Our review suggests that AF has an independent adverse prognostic impact on the clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease. PMID:26225200

  11. [Acute renal failure due to obstructive ureteral stone associated with norovirus gastroenteritis in an infant with congenital solitary kidney].

    PubMed

    Kato, Taiki; Hamano, Atsushi; Kawamura, Hideki

    2014-10-01

    We report a 35 month-old boy with acute renal failure caused by an obstructive ureteral stone associated with norovirus gastroenteritis. He visited his family physician because of fever, abdominal pain and vomiting. He was diagnosed as acute gastroenteritis. The symptoms relieved once, but abdominal pain and vomiting recurred two days after the visit and the volume of urine decreased. He was diagnosed as norovirus gastoenteritis and acute renal failure which was unresponsive to fluid replacement. Ultrasound study of the abdomen showed a solitary kidney with mild hydronephrosis. He was then admitted to our hospital. He was finally diagnosed as acute postrenal failure due to obstructive ureteral stone with left solitary kidney by abdominal computer tomography (CT). We performed transurethral catheterization immediately. The creatinine and blood urea nitrogen returned to normal level in 2 days. The CT performed on the 28th day post operation showed disappearance of the stone after uric alkalization. Recently, some cases of postrenal failure due to bilateral obstructive ureteral stones, mainly ammonium acid urate stones, associated with viral gastroenteritis were reported. As clinical features, they are common in boys three years or younger after an episode of rotavirus gastroenteritis with high uric acid concentration. By far, the most common cause of acute renal failure in patients with severe gastroenteritis is prerenal failure resulting from hypovolemia. But postrenal cause due to bilateral obstructive stones should be taken in a consideration.

  12. Early plasmapheresis in patients with severe hypertriglyceridemia induced acute pancreatitis.

    PubMed

    Nasa, Prashant; Alexander, George; Kulkarni, Amitabh; Juneja, Deven; Sehra, Sudhish; Agarwal, Rajesh; Koul, Kandy

    2015-08-01

    Hypertriglyceridemia can cause severe diseases such as acute pancreatitis (AP) and coronary artery disease. The routine management of hypertriglyceridemia is dietary restriction of fat and lipid-lowering medications to manage the secondary or precipitating causes of hypertriglyceridemia. However, in cases of AP with severe hypertriglyceridemia (SHTG) (triglycerides [TG] >1000 mg/dl) rapid reduction of TG levels to well below 1000 mg/dl can improve outcome and prevent further episodes of pancreatitis. Plasmapheresis is a therapeutic option in such medical emergencies. We discussed 2 cases of severe AP with SHTG where we used early plsmapheresis along with other supportive management. PMID:26321811

  13. Involvement of autophagy in the pharmacological effects of the mTOR inhibitor everolimus in acute kidney injury.

    PubMed

    Nakagawa, Shunsaku; Nishihara, Kumiko; Inui, Ken-ichi; Masuda, Satohiro

    2012-12-01

    Inhibitors of mammalian target of rapamycin (mTOR) have immunosuppressive and anti-cancer effects, but their effects on the progression of kidney disease are not fully understood. Using cells from normal kidney epithelial cell lines, we found that the antiproliferative effects of mTOR inhibitor everolimus accompanied the accumulation of a marker for cellular autophagic activity, the phosphatidylethanolamine-conjugated form of microtubule-associated protein 1 light chain 3 (LC3-II) in cells. We also showed that the primary autophagy factor UNC-51-like kinase 1 was involved in the antiproliferative effects of everolimus. Levels of LC3-II decreased in the kidneys of rats treated with ischemia-reperfusion or cisplatin; however, renal LC3-II levels increased after administration of everolimus to rats subjected to ischemia-reperfusion or cisplatin treatment. Simultaneously, increased signals for kidney injury molecule-1 and single-stranded DNA and decreased signals for Ki-67 in the proximal tubules were observed after treatment with everolimus, indicating that everolimus diminished renal function after acute tubular injury. We also found leakage of LC3 protein into rat urine after treatment with everolimus, and urinary LC3 protein was successfully measured between 0.1 and 500ng/mL by using an enzyme-linked immunosorbent assay. Urinary LC3 levels were increased after administration of everolimus to rats subjected to ischemia-reperfusion or cisplatin treatment, suggesting that renal LC3-II and urinary LC3 protein are new biomarkers for autophagy in acute kidney injury. Taken together, our results demonstrated that the induction of autophagy by everolimus aggravates tubular dysfunction during recovery from kidney injury. PMID:23022334

  14. Neutrophil Gelatinase-Associated Lipocalin as an Early Sign of Diabetic Kidney Injury in Children

    PubMed Central

    Yürük Yıldırım, Zeynep; Nayır, Ahmet; Yılmaz, Alev; Gedikbaşı, Asuman; Bundak, Rüveyde

    2015-01-01

    Objective: There is some evidence indicating that histopathological changes in type 1 diabetes mellitus (T1DM) emerge before onset of microalbuminuria. The aim of our study was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) levels can be considered as an early sign of diabetic kidney injury. Methods: Urine NGAL (uNGAL) levels and urinary NGAL/creatinine ratio (uNGAL/Cr) were assessed in 76 patients with T1DM and compared with the findings of 35 healthy individuals. The relationship of uNGAL levels with diabetes duration, body mass index (BMI), serum lipids, HbA1c, and microalbuminuria was also evaluated. Results: Mean uNGAL (100.16±108.28 ng/mL) and uNGAL/Cr (118.93-117.97 ng/mg) levels in both microalbuminuric and non-microalbuminuric diabetic patients were found to be higher than those in the control group (uNGAL: 21.46±18.59 ng/mL and uNGAL/Cr: 32.1±51.48 ng/mg) (p=0.0001). Conclusion: Urine NGAL level increases in the very early phase of T1DM before microalbuminuria develops. The patients with T1DM should be considered to have diabetic kidney injury from the time of diagnosis on and preventive interventions need to be initiated at an early stage to preclude the progression to end-stage renal disease. PMID:26777038

  15. Increased Risk of Acute Kidney Injury following Pneumococcal Pneumonia: A Nationwide Cohort Study

    PubMed Central

    Lin, Te-Yu; Chen, Yu-Guang; Lin, Cheng-Li; Kao, Chia-Hung

    2016-01-01

    Purpose Pneumococcal disease leads to renal complications ranging from persistent proteinuria to end-stage renal disease. Studies on the association between pneumococcal pneumonia (PP) and acute kidney injury (AKI) are scant. This study assessed the relationship between PP and risk of AKI. Methods This nationwide population-based cohort study examined data from the Taiwan National Health Insurance Research Database for the period 2000–2011. We identified inpatients with newly diagnosed PP according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. In addition, we selected a comparison cohort from inpatient claims without the diagnosis of PP that was randomly frequency-matched with the PP cohort according to age, sex, index year and comorbidities. We analyzed the risks of AKI by using Cox proportional hazards regression models, adjusted for sex, age, and comorbidities. Results A total of 10,069 patients with PP and 10,069 controls were enrolled in this study. After adjustments for age, sex, and comorbidities, patients with PP had a 1.11-fold risk of developing AKI compared with the comparison cohort. Conclusion This study indicates that AKI risks are higher in patients with PP compared with the comparison cohort. Careful follow-up observation and aggressive treatment are necessary for patients with PP to reduce the risk of AKI. PMID:27362355