Dental fluorosis, nutritional status, kidney damage, and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India.

PubMed

Khandare, Arjun L; Gourineni, Shankar Rao; Validandi, Vakdevi

2017-10-23

A case-control study was undertaken among the school children aged 8-15 years to know the presence and severity of dental fluorosis, nutrition and kidney status, and thyroid function along with bone metabolic indicators in Doda district situated at high altitude where drinking water was contaminated and heat stress. This study included 824 participants with an age of 8-15 years. The results of the study reviled that dental fluorosis was significantly higher in affected than control area children. Urinary fluoride was significantly higher (p < 0.05) in affected children as compared to the control area school children. Nutritional status of affected children was lower than control area children. The chronic kidney damage (CKD) was higher in affected than control school children. Thyroid function was affected more in affected than control area schools. Serum creatinine, total alkaline phosphatase, parathyroid hormone, 1, 25(OH) 2 vitamin D, and osteocalcin were significantly higher in affected school children (p < 0.05) as compared to control school children, whereas there was no significant difference in triiodothyronine (T3), thyroxine (T4), and 25-OH vitamin D among the two groups. There was a significant decrease in thyroid-stimulating hormone (TSH) in the affected area school children compared to control. In conclusion, fluorotic area school children were more affected with dental fluorosis, kidney damage, along and some bone indicators as compared to control school children.

Abnormalities in biomarkers of mineral and bone metabolism in kidney donors.

PubMed

Kasiske, Bertram L; Kumar, Rajiv; Kimmel, Paul L; Pesavento, Todd E; Kalil, Roberto S; Kraus, Edward S; Rabb, Hamid; Posselt, Andrew M; Anderson-Haag, Teresa L; Steffes, Michael W; Israni, Ajay K; Snyder, Jon J; Singh, Ravinder J; Weir, Matthew R

2016-10-01

Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy

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

Porter, Daniel S.; Pienkowski, David; Faugere, Marie-Claude

2012-01-01

Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bonemore » with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek to avoid low or high bone turnover and aim for turnover rates as close to normal as possible.« less

Management of mineral and bone disorder after kidney transplantation.

PubMed

Kalantar-Zadeh, Kamyar; Molnar, Miklos Z; Kovesdy, Csaba P; Mucsi, Istvan; Bunnapradist, Suphamai

2012-07-01

Mineral and bone disorders (MBDs), inherent complications of moderate and advanced chronic kidney disease, occur frequently in kidney transplant recipients. However, much confusion exists about the clinical application of diagnostic tools and preventive or treatment strategies to correct bone loss or mineral disarrays in transplanted patients. We have reviewed the recent evidence about prevalence and consequences of MBD in kidney transplant recipients and examined diagnostic, preventive and therapeutic options to this end. Low turnover bone disease occurs more frequently after kidney transplantation according to bone biopsy studies. The risk of fracture is high, especially in the first several months after kidney transplantation. Alterations in minerals (calcium, phosphorus and magnesium) and biomarkers of bone metabolism (parathyroid hormone, alkaline phosphatase, vitamin D and FGF-23) are observed with varying impact on posttransplant outcomes. Calcineurin inhibitors are linked to osteoporosis, whereas steroid therapy may lead to both osteoporosis and varying degrees of osteonecrosis. Sirolimus and everolimus might have a bearing on osteoblast proliferation and differentiation or decreasing osteoclast-mediated bone resorption. Selected pharmacologic interventions for the treatment of MBD in transplant patients include steroid withdrawal, and the use of bisphosphonates, vitamin D derivatives, calcimimetics, teriparatide, calcitonin and denosumab. MBD following kidney transplantation is common and characterized by loss of bone volume and mineralization abnormalities, often leading to low turnover bone disease. Although there are no well established therapeutic approaches for management of MBD in renal transplant recipients, clinicians should continue individualizing therapy as needed.

Management of Minerals and Bone Disorders after Kidney Transplantation

PubMed Central

Kalantar-Zadeh, Kamyar; Molnar, Miklos Z; Kovesdy, Csaba P.; Mucsi, Istvan; Bunnapradist, Suphamai

2012-01-01

Purpose of review Mineral and bone disorders (MBD), inherent complications of moderate and advanced chronic kidney disease (CKD), occur frequently in kidney transplant recipients. However, much confusion exists about clinical application of diagnostic tools and preventive or treatment strategies to correct bone loss or mineral disarrays in transplanted patients. We have reviewed the recent evidence about prevalence and consequences of MBD in kidney transplant recipients and examined diagnostic, preventive and therapeutic options to this end. Recent findings Low turnover bone disease occurs more frequently after kidney transplantation according to bone biopsy studies. The risk of fracture is high, especially in the first several months after kidney transplantation. Alterations in minerals (calcium, phosphorus and magnesium) and biomarkers of bone metabolism (PTH, alkaline phosphatase, vitamin D and FGF-23) are observed with varying impact on post-transplant outcomes. Calcineurin inhibitors are linked to osteoporosis, whereas steroid therapy may lead to both osteoporosis and varying degrees of osteonecrosis. Sirolimus and everolimus might have a bearing on osteoblasts proliferation and differentiation or decreasing osteoclast mediated bone resorption. Selected pharmacologic interventions for treatment of MBD in transplant patients include steroid withdrawal, the use of bisphosphonates, vitamin D derivatives, calcimimetics, teriparatide, calcitonin and denosumab. Summary MBD following kidney transplantation is common and characterized by loss of bone volume and mineralization abnormalities often leading to low turnover bone disease. Although there are no well-established therapeutic approaches for management of MBD in renal transplant recipients, clinicians should continue individualizing therapy as needed. PMID:22614626

Human water, sodium, and calcium regulation during space flight and exercise

NASA Astrophysics Data System (ADS)

Doty, S. E.; Seagrave, R. C.

When one is exposed to microgravity, fluid which is normally pooled in the lower extremities is redistributed headward and weight bearing bones begin to demineralize due to reduced mechanical stresses. The kidney, which is the primary regulator of body fluid volume and composition, responds to the fluid shift and bone demineralization by increasing the urinary output of water, sodium, and calcium. This research involves developing a mathematical description of how water and electrolytes are internally redistributed and exchanged with the environment during space flight. This model consequently involves kidney function and the associated endocrine system. The model agrees well with actual data, including that a low sodium diet can prevent bone demineralization. Therefore, assumptions made to develop the model are most likely valid. Additionally, various levels of activity are also considered in the model since exercise may help to eliminate some of the undesired effects of space flight such as muscle atrophy and bone demineralization.

Human water, sodium, and calcium regulation during space flight and exercise

NASA Astrophysics Data System (ADS)

Doty, S. E.; Seagrave, R. C.

2000-05-01

When one is exposed to microgravity, fluid which is normally pooled in the lower extremities is redistributed headward and weight bearing bones begin to demineralize due to reduced mechanical stresses. The kidney, which is the primary regulator of body fluid volume and composition, responds to the fluid shift and bone demineralization by increasing the urinary output of water, sodium, and calcium. This research involves developing a mathematical description of how water and electrolytes are internally redistributed and exchanged with the environment during space flight. This model consequently involves kidney function and the associated endocrine system. The model agrees well with actual data, including that a low sodium diet can prevent bone demineralization. Therefore, assumptions made to develop the model are most likely valid. Additionally, various levels of activity are also considered in the model since exercise may help to eliminate some of the undesired effects of space flight such as muscle atrophy and bone demineralization.

Direct reprogramming of human bone marrow stromal cells into functional renal cells using cell-free extracts.

PubMed

Papadimou, Evangelia; Morigi, Marina; Iatropoulos, Paraskevas; Xinaris, Christodoulos; Tomasoni, Susanna; Benedetti, Valentina; Longaretti, Lorena; Rota, Cinzia; Todeschini, Marta; Rizzo, Paola; Introna, Martino; Grazia de Simoni, Maria; Remuzzi, Giuseppe; Goligorsky, Michael S; Benigni, Ariela

2015-04-14

The application of cell-based therapies in regenerative medicine is gaining recognition. Here, we show that human bone marrow stromal cells (BMSCs), also known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O-permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes-formation of "domes" and tubule-like structures-and acquired epithelial functional properties such as transepithelial-resistance, albumin-binding, and uptake and specific markers E-cadherin and aquaporin-1. Transmission electron microscopy revealed the presence of brush border microvilli and tight intercellular contacts. RNA sequencing showed tubular epithelial transcript abundance and revealed the upregulation of components of the EGFR pathway. Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin-induced acute kidney injury engrafted into proximal tubuli, reduced renal injury and improved function. Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Resistance exercise training restores bone mineral density in renal transplant recipients.

PubMed

Eatemadololama, Ali; Karimi, Mohammad Taghi; Rahnama, Nader; Rasolzadegan, Mohammad Hoseynen

2017-01-01

The kidneys are complex organs of human body sustain a number of vital and important functions. These organs need to be replaced in some subjects due to various diseases. Bone mineral density (BMD) of the subjects with kidney transplantation reduced as a result of poor mobility and use of especial drugs. Due to lack of information regarding the influences of weight training exercise on BMD of long bone, this research was done. 24 subjects with history of kidney transplantation were recruited in this study. They were divided into two groups who received weight training exercise and control group. The BMD of femur and lumbar spine was measured by use of dual energy X-Ray absorptiometry in both groups. The difference between BMD was evaluated by use of two sample T test. The mean values of BMD of femur were 0.679±0.09 g/cm 2 and 0.689±0.09 before and after exercise in this first group. In contrast it was 0.643±0.11 before follow-up and 0.641±0.11 g/cm 2 after follow-up in the control group. There was no difference in BMD of lumbar spine after exercise. The result of this research study showed that BMD of long bone improved follow exercise. Therefore, it was concluded that weight training exercise can be used for the subjects with kidney transplantation.

Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function.

PubMed

Wang, Mengjing; Obi, Yoshitsugu; Streja, Elani; Rhee, Connie M; Lau, Wei Ling; Chen, Jing; Hao, Chuanming; Hamano, Takayuki; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-07-07

The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality. The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m 2 ) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011. A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance ( P interaction =0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance ( i.e. , <1.5 ml/min per 1.73 m 2 ), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance ( i.e. , ≥1.5 ml/min per 1.73 m 2 ; P interaction <0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk ( P trend <0.001 for both) irrespective of residual renal urea clearance strata ( P interaction =0.34 and P interaction =0.53, respectively). Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population. Copyright © 2017 by the American Society of Nephrology.

Genetic modification of mesenchymal stem cells to overexpress CXCR4 and CXCR7 does not improve the homing and therapeutic potentials of these cells in experimental acute kidney injury.

PubMed

Gheisari, Yousof; Azadmanesh, Kayhan; Ahmadbeigi, Naser; Nassiri, Seyed Mahdi; Golestaneh, Azadeh Fahim; Naderi, Mahmood; Vasei, Mohammad; Arefian, Ehsan; Mirab-Samiee, Siamak; Shafiee, Abbas; Soleimani, Masoud; Zeinali, Sirous

2012-11-01

The therapeutic potential of bone marrow mesenchymal stem cells (MSCs) in kidney failure has been examined in some studies. However, recent findings indicate that after transplantation, these cells home to kidneys at very low levels. Interaction of stromal derived factor-1 (SDF-1) with its receptor, CXCR4, is of pivotal importance in migration and homing. Recently, CXCR7 has also been recognized as another SDF-1 receptor that interacts with CXCR4 and modulates its functions. In this study, CXCR4 and CXCR7 were separately and simultaneously overexpressed in BALB/c bone marrow MSCs by using a lentiviral vector system and the homing and renoprotective potentials of these cells were evaluated in a mouse model of cisplatin-induced acute kidney injury. Using flow cytometry, immunohistochemistry, and real-time PCR methods for detection of GFP-labeled MSCs, we found that although considerably entrapped in lungs, native MSCs home very rarely to kidneys and bone marrow and this rate cannot be significantly affected by CXCR4 and/or CXCR7 upregulation. Transplantation of neither native nor genetically engineered MSCs ameliorated kidney failure. We concluded that overexpression of CXCR4 and CXCR7 receptors in murine MSCs cannot improve the homing and therapeutic potentials of these cells and it can be due to severe chromosomal abnormalities that these cells bear during ex vivo expansion.

Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Daya, Natalie; Voskertchian, Annie; Schneider, Andrea L C; Ballew, Shoshana; McAdams DeMarco, Mara; Coresh, Josef; Appel, Lawrence J; Selvin, Elizabeth; Grams, Morgan E

2016-02-01

People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers. Prospective cohort study. 10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio, and alternative filtration markers. Fracture-related hospitalizations determined by diagnostic code. Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists. Mean age of participants was 63 years, 56% were women, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk for fracture (P<0.001). The relationship between eGFRcr and fracture risk was nonlinear: <60mL/min/1.73m(2), lower eGFRcr was associated with higher fracture risk (adjusted HR per 10mL/min/1.73m(2) lower, 1.24; 95% CI, 1.05-1.47); there was no statistically significant association for ≥60mL/min/1.73m(2) in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including albumin-creatinine ratio (HR per doubling, 1.10; 95% CI, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06-1.25), and 1/β2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15-1.37). No bone mineral density assessment; one-time measurement of kidney function. Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Safety Considerations in the Use of Ketorolac for Postoperative Pain.

PubMed

Maslin, Benjamin; Lipana, Lawrence; Roth, Brandon; Kodumudi, Gopal; Vadivelu, Nalini

2017-01-01

Ketorolac use has significantly expanded for postoperative pain management since it first became available in the United States, primarily due to well established effects on patient pain scores and its ability to reduce perioperative opioid requirements. As an inhibitor of cyclooxygenase, ketorolac use has raised clinical concern including particular controversy regarding its potential effects on bone healing, postoperative kidney function and perioperative bleeding. To review the supporting data from clinical studies addressing the safety of ketorolac use for postoperative pain. This review highlights the most up-to-date research from clinical trials as well as from retrospective studies and meta-analyses regarding the effects of perioperative use of ketorolac on bone healing, kidney function and blood loss. Based on the most up-to-date literature, ketorolac in normal doses has been demonstrated to be safe with respect to bone healing. In patients with normal kidney function, numerous studies have established the safety of Ketorolac; however other studies have raised safety concerns in patients with comorbid kidney, heart and liver disease. While there is evidence that ketorolac may cause prolonged bleeding time and may be associated with increased postoperative blood loss after tonsillectomy, large scale prospective randomized controlled trials and subsequent meta-analyses have failed to establish an association of ketorolac use and perioperative blood loss. Perioperative administration of ketorolac has been demonstrated to be safe and effective in healthy patients and is particularly beneficial as an opioid-sparing agent in vulnerable patient groups. However, in certain surgical and medical contexts, proper patient selection based on the multidisciplinary collaboration between perioperative clinician specialists will optimize patient safety and pain management outcomes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The chemokine receptor CXCR6 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis

PubMed Central

Xia, Yunfeng; Yan, Jingyin; Jin, Xiaogao; Entman, Mark L.; Wang, Yanlin

2014-01-01

Bone marrow-derived fibroblasts in circulation are of hematopoietic origin, proliferate, differentiate into myofibroblasts, and express the chemokine receptor CXCR6. Since chemokines mediate the trafficking of circulating cells to sites of injury, we studied the role of CXCR6 in mouse models of renal injury. Significantly fewer bone marrow-derived fibroblasts accumulated in the kidney of CXCR6 knockout mice in response to injury, expressed less profibrotic chemokines and cytokines, displayed fewer myofibroblasts, and expressed less α-smooth muscle actin in the obstructed kidneys compared with wild-type mice. CXCR6 deficiency inhibited total collagen deposition and suppressed expression of collagen I and fibronectin in the obstructed kidneys. Furthermore, wild type mice engrafted with CXCR6−/− bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidneys with obstructive injury and showed less severe renal fibrosis compared with wild-type mice engrafted with CXCR6+/+ bone marrow cells. Transplant of wild type bone marrow into CXCR6−/− recipients restored recruitment of myeloid fibroblasts and susceptibility to fibrosis. Hematopoietic fibroblasts migrate into injured kidney and proliferate and differentiate into myofibroblasts. Thus, CXCR6, together with other chemokines and their receptors, may play important roles in the recruitment of bone marrow-derived fibroblast precursors into the kidney and contribute to the pathogenesis of renal fibrosis. PMID:24646857

The chemokine receptor CXCR6 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis.

PubMed

Xia, Yunfeng; Yan, Jingyin; Jin, Xiaogao; Entman, Mark L; Wang, Yanlin

2014-08-01

Bone marrow-derived fibroblasts in circulation are of hematopoietic origin, and they proliferate, differentiate into myofibroblasts, and express the chemokine receptor CXCR6. As chemokines mediate the trafficking of circulating cells to sites of injury, we studied the role of CXCR6 in mouse models of renal injury. Significantly, the kidney of CXCR6 knockout mice accumulated fewer bone marrow-derived fibroblasts in response to injury, expressed less profibrotic chemokines and cytokines, displayed fewer myofibroblasts, and expressed less α-smooth muscle actin in the obstructed kidneys compared with wild-type (WT) mice. CXCR6 deficiency inhibited total collagen deposition and suppressed the expression of collagen I and fibronectin in the obstructed kidneys. Furthermore, WT mice engrafted with CXCR6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the kidneys with obstructive injury and showed less severe renal fibrosis compared with WT mice engrafted with CXCR6(+/+) bone marrow cells. Transplant of WT bone marrow into CXCR6(-/-) recipients restored recruitment of myeloid fibroblasts and susceptibility to fibrosis. Hematopoietic fibroblasts migrate into injured kidney and proliferate and differentiate into myofibroblasts. Thus, CXCR6, together with other chemokines and their receptors, may have important roles in the recruitment of bone marrow-derived fibroblast precursors into the kidney and contribute to the pathogenesis of renal fibrosis.

Stem cells in nephrology: present status and future.

PubMed

Watorek, Ewa; Klinger, Marian

2006-01-01

Stem cell biology is currently developing rapidly because of the potential therapeutic utility of stem cells. The ability to acquire any desired phenotype raises hope for regenerative therapies. Manipulation of these cells is a potentially valuable tool; however, the mechanisms of stem cell differentiation and plasticity are currently beyond our control. In the field of nephrology, the presence of adult kidney stem cells has been debated. Renal adult stem cells may be descendants of some early kidney progenitors, or may be derived from bone marrow. Evidence of a hematopoietic stem-cell contribution to renal repair encourages the possibility of bone marrow or stem cell transplantation as a means of treating autoimmune glomerulopathies. The transplantation of fetal kidney tissue containing renal progenitors, which then develop into functional nephrons, is a step towards renal regeneration. According to recent reports, the development of functional nephrons from human mesenchymal stem cells in rodent whole-embryo culture is possible. Establishing in vitro self organs from autologous stem cells would be a promising therapeutic solution in light of the shortage of allogenic organs and the unresolved problem of chronic allograft rejection.

Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation.

PubMed

Schreiber, Peter W; Bischoff-Ferrari, Heike A; Boggian, Katia; Bonani, Marco; van Delden, Christian; Enriquez, Natalia; Fehr, Thomas; Garzoni, Christian; Hirsch, Hans H; Hirzel, Cédric; Manuel, Oriol; Meylan, Pascal; Saleh, Lanja; Weisser, Maja; Mueller, Nicolas J

2018-01-01

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; P<0.001) and median intact parathyroid hormone levels decreased by 68.4% (from 208.7 to 66.0 ng/l; P<0.001). Median β-Crosslaps (CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) decreased by 65.1% (from 1.32 to 0.46ng/ml; P<0.001) and 60.6% (from 158.2 to 62.3ng/ml; P<0.001), respectively. Kidney recipients with incident fractures had significantly lower levels of 1, 25-(OH)2 vitamin D at time of transplantation and of intact parathyroid hormone 6 months post-transplant. Among 70 liver recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone levels were not significantly altered between peri-transplant and 6 months post-transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from 0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P = 0.001) in the longitudinal course. Assessed biomarkers didn't differ between liver recipients with and without fractures. To conclude, the assessed panel of biomarkers proved highly dynamic after liver as well as kidney transplantation in the early post-transplant period. After kidney transplantation a significant gain in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas after liver transplantation an increase in CTx and P1NP were characteristic.

Occupational Exposure to HIV: Advice for Health Care Workers

MedlinePlus

... kidney, and bone marrow function. Another option is post-exposure prophylaxis (PEP). This treatment suppresses the HIV virus to prevent infection. If you still test positive, the treatment can help decrease the virus’ ...

Cadmium-induced bone effect is not mediated via low serum 1,25-dihydroxy vitamin D

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

Engstroem, Annette; Skerving, Staffan; Lidfeldt, Jonas

Cadmium is a widespread environmental pollutant, which is associated with increased risk of osteoporosis. It has been proposed that cadmium's toxic effect on bone is exerted via impaired activation of vitamin D, secondary to the kidney effects. To test this, we assessed the association of cadmium-induced bone and kidney effects with serum 1,25-dihydroxyvitamin D (1,25(OH){sub 2}D); measured by enzyme immunoassay. For the assessment, we selected 85 postmenopausal women, based on low (0.14-0.39 {mu}g/L) or high (0.66-2.1 {mu}g/L) urinary cadmium, within a cross-sectional population-based women's health survey in Southern Sweden. We also measured 25-hydroxy vitamin D, cadmium in blood, bone mineralmore » density and several markers of bone remodeling and kidney effects. Although there were clear differences in both kidney and bone effect markers between women with low and high cadmium exposure, the 1,25(OH){sub 2}D concentrations were not significantly different (median, 111 pmol/L (5-95th percentile, 67-170 pmol/L) in low- and 125 pmol/L (66-200 pmol/L) in high-cadmium groups; p=0.08). Also, there was no association between 1,25(OH){sub 2}D and markers of bone or kidney effects. It is concluded that the low levels of cadmium exposure present in the studied women, although high enough to be associated with lower bone mineral density and increased bone resorption, were not associated with lower serum concentrations of 1,25(OH){sub 2}D. Hence, decreased circulating levels of 1,25(OH){sub 2}D are unlikely to be the proposed link between cadmium-induced effects on kidney and bone.« less

Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.

PubMed

Prochaska, Megan; Taylor, Eric; Vaidya, Anand; Curhan, Gary

2017-08-07

Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). Low bone density is an independent risk factor for incident kidney stone and is associated with higher 24-hour urine calcium excretion. Among participants with low bone density, bisphosphonate use was associated with lower risk of incident kidney stone but was not independently associated with 24-hour urine calcium excretion. Copyright © 2017 by the American Society of Nephrology.

Kidney repair using stem cells: myth or reality as a therapeutic option?

PubMed

Iwatani, Hirotsugu; Imai, Enyu

2010-01-01

The kidney has been considered a highly terminally differentiated organ of the body, and its proliferative potential is low, with the result that it has been thought of as a most unlikely organ for regeneration. From the structural point of view, the kidney is elaborately composed of many cell types that function as a tissue unit and not as individual cells, which also makes it more difficult to regenerate. However, in clinical settings, the kidney does have regenerative potential as seen in the recovery from acute kidney injury. The role of bone marrow-derived mesenchymal stromal cells may mainly be to produce humoral factors accelerating regeneration. The origin, localization and role of kidney stem cells are under investigation. We also discuss potential applications of embryonic stem cells and induced pluripotent stem cells in kidney regeneration.

From "Kidneys Govern Bones" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science.

PubMed

Wang, Xiao-Qin; Zou, Xin-Rong; Zhang, Yuan Clare

2016-01-01

Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

Crucial Role of Vitamin D in the Musculoskeletal System

PubMed Central

Wintermeyer, Elke; Ihle, Christoph; Ehnert, Sabrina; Stöckle, Ulrich; Ochs, Gunnar; de Zwart, Peter; Flesch, Ingo; Bahrs, Christian; Nussler, Andreas K.

2016-01-01

Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D’s central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported. PMID:27258303

Crucial Role of Vitamin D in the Musculoskeletal System.

PubMed

Wintermeyer, Elke; Ihle, Christoph; Ehnert, Sabrina; Stöckle, Ulrich; Ochs, Gunnar; de Zwart, Peter; Flesch, Ingo; Bahrs, Christian; Nussler, Andreas K

2016-06-01

Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D's central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported.

The systemic nature of CKD.

PubMed

Zoccali, Carmine; Vanholder, Raymond; Massy, Ziad A; Ortiz, Alberto; Sarafidis, Pantelis; Dekker, Friedo W; Fliser, Danilo; Fouque, Denis; Heine, Gunnar H; Jager, Kitty J; Kanbay, Mehmet; Mallamaci, Francesca; Parati, Gianfranco; Rossignol, Patrick; Wiecek, Andrzej; London, Gerard

2017-06-01

The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy.

Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation

PubMed Central

Pereira, Renata C.; Valta, Helena; Tumber, Navdeep; Salusky, Isidro B.; Jalanko, Hannu

2015-01-01

Background Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function. Methods Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies. Results FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01). Conclusions Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation. PMID:26390291

Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation.

PubMed

Pereira, Renata C; Valta, Helena; Tumber, Navdeep; Salusky, Isidro B; Jalanko, Hannu; Mäkitie, Outi; Wesseling Perry, Katherine

2015-01-01

Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function. Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies. FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01). Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation.

Bone marrow-mesenchymal stromal cell infusion in patients with chronic kidney disease: A safety study with 18 months of follow-up.

PubMed

Makhlough, Atieh; Shekarchian, Soroosh; Moghadasali, Reza; Einollahi, Behzad; Dastgheib, Mona; Janbabaee, Ghasem; Hosseini, Seyedeh Esmat; Falah, Nasrin; Abbasi, Fateme; Baharvand, Hossein; Aghdami, Nasser

2018-05-01

Chronic kidney disease (CKD) is a progressive loss of kidney function and structure that affects approximately 13% of the population worldwide. A recent meta-analysis revealed that cell-based therapies improve impaired renal function and structure in preclinical models of CKD. We assessed the safety and tolerability of bone marrow-mesenchymal stromal cell (MSC) infusion in patients with CKD. A single-arm study was carried out at one center with 18-month follow-up in seven eligible patients with CKD due to different etiologies such as hypertension, nephrotic syndrome (NS) and unknown etiology. We administered an intravenous infusion (1-2 × 10 6 cells/kg) of autologous cultured MSCs. The primary endpoint was safety, which was measured by number and severity of adverse events. The secondary endpoint was decrease in the rate of decrease in estimated glomerular filtration rate (eGFR). We compared kidney function during the follow-up visits to baseline and 18 months prior to the intervention. Follow-up visits of all seven patients were completed; however, we have not observed any cell-related adverse events during the trial. Changes in eGFR (P = 0.10) and serum creatinine (P = 0.24) from 18 months before cell infusion to baseline in comparison with baseline to 18 months were not statistically significant. We showed safety and tolerability of a single-dose infusion of autologous MSCs in patients with CKD. Copyright © 2018. Published by Elsevier Inc.

Individualized therapy to prevent bone mineral density loss after kidney and kidney-pancreas transplantation.

PubMed

Mainra, Rahul; Elder, Grahame J

2010-01-01

Most patients who undergo kidney or kidney-pancreas transplantation have renal osteodystrophy, and immediately after transplantation bone mineral density (BMD) commonly falls. Together, these abnormalities predispose to an increased fracture incidence. Bisphosphonate or calcitriol therapy can preserve BMD after transplantation, but although bisphosphonates may be more effective, they pose potential risks for adynamic bone. A total of 153 kidney (61%) and kidney-pancreas (39%) transplant recipients were allocated to bisphosphonate (62%) or calcitriol (38%) therapy using an algorithm that incorporated BMD, prevalent vertebral fracture, biomarkers of bone turnover, and risk factor assessment. Patients received cholecalciferol and calcium as appropriate and were followed for 12 mo. Patients who were treated with bisphosphonates had lower BMD at the lumbar spine and femoral neck and longer time on dialysis. Age and gender were similar between the groups. At 12 mo, bisphosphonate-treated patients had significant BMD increases at the lumber spine and femoral neck and a negative trend at the wrist. Patients who were allocated to calcitriol, who were assessed to have lower baseline fracture risk, had no significant change in BMD at any site. At 1 yr, mean levels of bone turnover marker and intact parathyroid hormone normalized in both groups. Incident fracture rates did not differ significantly. With targeted treatment, BMD levels were stable or improved and bone turnover markers normalized. This algorithm provides a guide to targeting therapy after transplantation that avoids BMD loss and may reduce suppression of bone turnover.

Increasing dietary phosphorus intake from food additives: potential for negative impact on bone health.

PubMed

Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

2014-01-01

It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These findings suggest that long-term dietary phosphorus loads and long-term hyperphosphatemia may have important negative effects on bone health. In contrast, PTH concentrations did not increase as a result of high dietary phosphorus intake when phosphorus was provided with adequate amounts of calcium. Intake of foods with a ratio of calcium to phosphorus close to that found in dairy products led to positive effects on bone health. Several randomized controlled trials have shown positive relations between dairy intake and bone mineral density. In our loading test with a low-calcium, high-phosphorus lunch provided to healthy young men, serum PTH concentrations showed peaks at 1 and 6 h, and serum fibroblast growth factor 23 (FGF23) concentrations increased significantly at 8 h after the meal. In contrast, the high-calcium, high-phosphorus meal suppressed the second PTH and FGF23 elevations until 8 h after the meal. This implies that adequate dietary calcium intake is needed to overcome the interfering effects of high phosphorus intake on PTH and FGF23 secretion. FGF23 acts on the parathyroid gland to decrease PTH mRNA and PTH secretion in rats with normal kidney function. However, increased serum FGF23 is an early alteration of mineral metabolism in chronic kidney disease, causing secondary hyperthyroidism, and implying resistance of the parathyroid gland to the action of FGF23 in chronic kidney disease. These findings suggest that long-term high-phosphorus diets may impair bone health mediated by FGF23 resistance both in chronic kidney disease patients and in the healthy population.

Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Schneider, Andrea L.C.; Ballew, Shoshana; McAdams DeMarco, Mara; Coresh, Josef; Appel, Lawrence J.; Selvin, Elizabeth; Grams, Morgan E.

2015-01-01

Background People with end-stage renal disease are at high risk of bone fracture. Less is known about fracture risk in milder chronic kidney disease (CKD), and whether CKD-associated fracture risk varies by sex or assessment with alternative kidney markers. Study Design Prospective cohort study. Setting & Participants 10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. Predictor Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio (ACR), and alternative filtration markers. Outcomes Fracture-related hospitalizations determined by diagnostic code. Measurements Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists. Results Mean age of participants was 63 years, 56% were female, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk of fracture (p<0.001). The relationship between eGFRcr and fracture risk was non-linear: below 60 ml/min/1.73 m2, lower eGFRcr was associated with higher fracture risk (adjusted HR per 10 ml/min/1.73 m2 lower, 1.24; 95% CI, 1.05–1.47); there was no statistically significant association above 60 ml/min/1.73 m2 in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including ACR (HR per doubling, 1.10; 95% CI, 1.06–1.14), cystatin C–based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06–1.25), and 1/β2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15–1.37). Limitations No bone mineral density assessment; one-time measure of kidney function. Conclusions Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation. PMID:26250781

An Association between BK Virus Replication in Bone Marrow and Cytopenia in Kidney-Transplant Recipients

PubMed Central

Pambrun, Emilie; Mengelle, Catherine; Fillola, Geneviève; Laharrague, Patrick; Esposito, Laure; Cardeau-Desangles, Isabelle; Del Bello, Arnaud; Izopet, Jacques; Rostaing, Lionel; Kamar, Nassim

2014-01-01

The human polyomavirus BK (BKV) is associated with severe complications, such as ureteric stenosis and polyomavirus-associated nephropathy (PVAN), which often occur in kidney-transplant patients. However, it is unknown if BKV can replicate within bone marrow. The aim of this study was to search for BKV replication within the bone marrow of kidney-transplant patients presenting with a hematological disorder. Seventy-two kidney-transplant patients underwent bone-marrow aspiration for cytopenia. At least one virus was detected in the bone marrow of 25/72 patients (35%), that is, parvovirus B19 alone (n = 8), parvovirus plus Epstein-Barr virus (EBV) (n = 3), cytomegalovirus (n = 4), EBV (n = 2), BKV alone (n = 7), and BKV plus EBV (n = 1). Three of the eight patients who had BKV replication within the bone marrow had no detectable BKV replication in the blood. Neutropenia was observed in all patients with BKV replication in the bone marrow, and blockade of granulocyte maturation was observed. Hematological disorders disappeared in all patients after doses of immunosuppressants were reduced. In conclusion, an association between BKV replication in bone marrow and hematological disorders, especially neutropenia, was observed. Further studies are needed to confirm these findings. PMID:24868448

The intervention effect of zuogui pill on chronic kidney disease-mineral and bone disorder regulatory factor.

PubMed

Ma, Xiaohong; He, Liqun

2018-06-24

Chronic kidney disease-mineral and bone disorder (CKD-MBD) play a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). Zuogui pill as a traditional Chinese herbal drug has been used for nourish kidney essence improve bone malnutrition of renal bone disease by regulating the metabolism of calcium and phosphorus and participating in osteoblast metabolism. In the present study, 5/6 nephrectomy rat model was used to reveal the mechanism of zuogui pill in treatment of CKD-MBD. Compared with sham rats, the levels of serum phosphorus, PTH, iPTH and creatinine were significantly decreased, while the serum calcium level was significantly increased, and the Cbfa1 protein level was significantly decreased and FGF23 protein level was significantly increased by Zuogui pill treatment. Compared with model rats, the BMD of rat was significantly increased by Zuogui pill treatment. Histological analysis revealed that the kidney injury of rats with CKD was significantly reduced by zuogui pill treatment. Compared with model rats, the CYP27B1 mRNA level was significantly increased, and the PTH mRNA level and NaPiIIa protein level were significantly decreased in the kidney by zuogui pill treatment. We inferred that zuogui pill exhibited potential therapeutic effects on CKD-MBD in the rats by regulating bone metabolism and nourish kidney. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Blood disorders typically associated with renal transplantation

PubMed Central

Yang, Yu; Yu, Bo; Chen, Yun

2015-01-01

Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival. PMID:25853131

Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation

PubMed Central

Schreiber, Peter W.; Bischoff-Ferrari, Heike A.; Boggian, Katia; Bonani, Marco; van Delden, Christian; Enriquez, Natalia; Fehr, Thomas; Garzoni, Christian; Hirsch, Hans H.; Hirzel, Cédric; Manuel, Oriol; Meylan, Pascal; Saleh, Lanja; Weisser, Maja

2018-01-01

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; P<0.001) and median intact parathyroid hormone levels decreased by 68.4% (from 208.7 to 66.0 ng/l; P<0.001). Median β-Crosslaps (CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) decreased by 65.1% (from 1.32 to 0.46ng/ml; P<0.001) and 60.6% (from 158.2 to 62.3ng/ml; P<0.001), respectively. Kidney recipients with incident fractures had significantly lower levels of 1, 25-(OH)2 vitamin D at time of transplantation and of intact parathyroid hormone 6 months post-transplant. Among 70 liver recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone levels were not significantly altered between peri-transplant and 6 months post-transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from 0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P = 0.001) in the longitudinal course. Assessed biomarkers didn’t differ between liver recipients with and without fractures. To conclude, the assessed panel of biomarkers proved highly dynamic after liver as well as kidney transplantation in the early post-transplant period. After kidney transplantation a significant gain in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas after liver transplantation an increase in CTx and P1NP were characteristic. PMID:29338022

Kidney tubular-cell secretion of osteoblast growth factor is increased by kaempferol: a scientific basis for "the kidney controlling the bone" theory of Chinese medicine.

PubMed

Long, Mian; Li, Shun-xiang; Xiao, Jiang-feng; Wang, Jian; Lozanoff, Scott; Zhang, Zhi-guang; Luft, Benjamin J; Johnson, Francis

2014-09-01

To study, at the cytological level, the basic concept of Chinese medicine that "the Kidney (Shen) controls the bone". Kaempferol was isolated form Rhizoma Drynariae (Gu Sui Bu, GSB) and at several concentrations was incubated with opossum kidney (OK) cells, osteoblasts (MC3T3 E1) and human fibroblasts (HF) at cell concentrations of 2×10(4)/mL. Opossum kidney cell-conditioned culture media with kaempferol at 70 nmol/L (70kaeOKM) and without kaempferol (0OKM) were used to stimulate MC3T3 E1 and HF proliferation. The bone morphological protein receptors I and II (BMPR I and II) in OK cells were identified by immune-fluorescence staining and Western blot analysis. Kaempferol was found to increase OK cell growth (P<0.05), but alone did not promote MC3T3 E1 or HF cell proliferation. However, although OKM by itself increased MC3T3 E1 growth by 198% (P<0.01), the 70kaeOKM further increased the growth of these cells by an additional 127% (P<0.01). It indicates that the kidney cell generates a previously unknown osteoblast growth factor (OGF) and kaempferol increases kidney cell secretion of OGF. Neither of these media had any significant effect on HF growth. Kaempferol also was found to increase the level of the BMPR II in OK cells. This lends strong support to the original idea that the Kidney has a significant influence over bone-formation, as suggested by some long-standing Chinese medical beliefs, kaempferol may also serve to stimulate kidney repair and indirectly stimulate bone formation.

Role of TGF-β in a mouse model of high turnover renal osteodystrophy.

PubMed

Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

2014-01-01

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore, our data suggest that elevated TGF-β may contribute to the pathogenesis of high-turnover disease partially through inhibition of β-catenin signaling. © 2014 American Society for Bone and Mineral Research.

Origin and function of myofibroblasts in kidney fibrosis.

PubMed

LeBleu, Valerie S; Taduri, Gangadhar; O'Connell, Joyce; Teng, Yingqi; Cooke, Vesselina G; Woda, Craig; Sugimoto, Hikaru; Kalluri, Raghu

2013-08-01

Myofibroblasts are associated with organ fibrosis, but their precise origin and functional role remain unknown. We used multiple genetically engineered mice to track, fate map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Through this comprehensive analysis, we identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts through proliferation. The nonproliferating myofibroblasts derive through differentiation from bone marrow (35%), the endothelial-to-mesenchymal transition program (10%) and the epithelial-to-mesenchymal transition program (5%). Specific deletion of Tgfbr2 in α-smooth muscle actin (αSMA)(+) cells revealed the importance of this pathway in the recruitment of myofibroblasts through differentiation. Using genetic mouse models and a fate-mapping strategy, we determined that vascular pericytes probably do not contribute to the emergence of myofibroblasts or fibrosis. Our data suggest that targeting diverse pathways is required to substantially inhibit the composite accumulation of myofibroblasts in kidney fibrosis.

Origin and Function of Myofibroblasts in Kidney Fibrosis

PubMed Central

LeBleu, Valerie S.; Taduri, Gangadhar; O’Connell, Joyce; Teng, Yingqi; Cooke, Vesselina G.; Woda, Craig; Sugimoto, Hikaru; Kalluri, Raghu

2014-01-01

Myofibroblasts are associated with organ fibrosis but their precise origin and functional role remain unknown. We employed multiple genetically engineered mice to track, fate-map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Such comprehensive analysis identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts via proliferation. The non-proliferating myofibroblasts derive via differentiation from bone marrow (35%), endothelial to mesenchymal transition (EndMT) program (10%) and epithelial to mesenchymal transition (EMT) program (5%). Specific deletion of Tgfbr2 in αSMA+ cells revealed the importance of this pathway in recruitment of myofibroblasts via differentiation. Using genetic mouse models and fate-mapping strategy we determined that vascular pericytes likely do not contribute to the emergence of myofibroblasts or fibrosis. This study suggests that targeting diverse pathways is required to significantly inhibit composite accumulation of myofibroblasts in kidney fibrosis. PMID:23817022

Local application of osteoprotegerin-chitosan gel in critical-sized defects in a rabbit model

PubMed Central

2017-01-01

Background Osteoprotegerin (OPG) is used for the systemic treatment of bone diseases, although it has many side effects. The aim of this study was to investigate a newly formulated OPG-chitosan gel for local application to repair bone defects. Recent studies have reported that immunodetection of osteopontin (OPN) and osteocalcin (OC) can be used to characterise osteogenesis and new bone formation. Methods The osteogenic potential of the OPG-chitosan gel was evaluated in rabbits. Critical-sized defects were created in the calvarial bone, which were either left unfilled (control; group I), or filled with chitosan gel (group II) or OPG-chitosan gel (group III), with rabbits sacrificed at 6 and 12 weeks. Bone samples from the surgical area were decalcified and treated with routine histological and immunohistochemical protocols using OC, OPN, and cathepsin K (osteoclast marker) antibodies. The toxicity of the OPG-chitosan gel was evaluated by biochemical assays (liver and kidney function tests). Results The mean bone growth in defects filled with the OPG-chitosan gel was significantly higher than those filled with the chitosan gel or the unfilled group (p < 0.05). At 6 and 12 weeks, the highest levels of OC and OPN markers were found in the OPG-chitosan gel group, followed by the chitosan gel group. The number of osteoclasts in the OPG-chitosan gel group was lower than the other groups. The results of the liver and kidney functional tests indicated no signs of harmful systemic effects of treatment. In conclusion, the OPG-chitosan gel has many characteristics that make it suitable for bone repair and regeneration, highlighting its potential benefits for tissue engineering applications. PMID:28674665

Bioinorganic Activity of Technetium Radiopharmaceuticals.

ERIC Educational Resources Information Center

Pinkerton, Thomas C.; And Others

1985-01-01

Technetium radiopharmaceuticals are diagnostic imaging agents used in the field of nuclear medicine to visualize tissues, anatomical structures, and metabolic disorders. Bioavailability of technetium complexes, thyroid imaging, brain imaging, kidney imaging, imaging liver function, bone imaging, and heart imaging are the major areas discussed. (JN)

Role of TGF-β in a Mouse Model of High Turnover Renal Osteodystrophy†

PubMed Central

Liu, Shiguang; Song, Wenping; Boulanger, Joseph H; Tang, Wen; Sabbagh, Yves; Kelley, Brian; Gotschall, Russell; Ryan, Susan; Phillips, Lucy; Malley, Katie; Cao, Xiaohong; Xia, Tai-He; Zhen, Gehua; Cao, Xu; Ling, Hong; Dechow, Paul C; Bellido, Teresita M; Ledbetter, Steven R; Schiavi, Susan C

2014-01-01

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystropy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-βs role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. μCT confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum PTH levels indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore, our data suggests that elevated TGF-β may contribute to the pathogenesis of high turnover disease partially through inhibition of β-catenin signaling. PMID:24166835

From “Kidneys Govern Bones” to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science

PubMed Central

Zou, Xin-Rong

2016-01-01

Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of “Kidneys Govern Bones.” Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes. PMID:27668003

Clinical observation on 96 cases of primary osteoporosis treated with kidney-tonifying and bone-strengthening mixture.

PubMed

Mingyue, Wang; Ling, Gong; Bei, Xia; Junqing, Cao; Peiqing, Zhou; Jie, Hu

2005-06-01

To objectively evaluate the therapeutic effect and safety of Mixture for Nourishing Kidney and Strengthening Bone. Among 160 cases of osteoporosis under clinical observation, 96 patients in the treatment group were treated with Mixture for Nourishing Kidney and Strengthening Bone, 32 patients in the control group were given Shen Gu Capsule and 32 patients in the blank group were given no drug in half a year. Observation and determination were conducted on bone mineral density (BMD), clinical symptoms, bone gla protein (BGP), pyridinoline (PYD), estradiol (E2), testosterone (T), blood urea nitrogen (BUN), transaminase and routine test on blood and urine. The comprehensive effect in the treatment group was remarkably superior to that in the control group. The safe and reliable Chinese drug can enhance BMD, promote osteogenesis and inhibit bone absorption, hence treating osteoporosis with marked effect.

Osteo-Renal Regulation of Systemic Phosphate Metabolism

PubMed Central

Razzaque, Mohammed Shawkat

2011-01-01

Summary Impaired kidney function and subsequent skeletal responses play a critical role in disrupting phosphate balance in chronic kidney disease (CKD) patients with mineral and bone disorder (CKD-MBD). In patients with CKD-MBD, the inability of the kidney to maintain normal mineral ion balance affects bone remodeling to induce skeletal fracture and extraskeletal vascular calcification. In physiological conditions, bone-derived fibroblast growth factor 23 (FGF23) acts on the kidney to reduce serum phosphate and 1,25-dihydroxyvitamin D levels. In humans, increased bioactivity of FGF23 leads to increased urinary phosphate excretion, which induces hypophosphatemic diseases (e.g., rickets/osteomalacia). However, reduced FGF23 activity is associated with hyperphosphatemic diseases (e.g., tumoral calcinosis). In patients with CKD, high serum levels of FGF23 fail to reduce serum phosphate levels and lead to numerous complications, including vascular calcification, one of the important determinants of mortality of CKD-MBD patients. Of particular significance, molecular, biochemical and morphological changes in patients with CKD-MBD are mostly due to osteo-renal dysregulation of mineral ion metabolism. Furthermore, hyperphosphatemia can partly contribute to the development of secondary hyperparathyroidism in patients with CKD-MBD. Relatively new pharmacological agents including sevelamer hydrochloride, calcitriol analogs and cinacalcet hydrochloride are used either alone, or in combination, to minimize hyperphosphatemia and hyperparathyroidism associated complications to improve morbidity and mortality of CKD-MBD patients. This article will briefly summarize how osteo-renal miscommunication can induce phosphate toxicity, resulting in extensive tissue injuries. PMID:21438115

Osteo-renal regulation of systemic phosphate metabolism.

PubMed

Razzaque, Mohammed Shawkat

2011-04-01

Impaired kidney function and subsequent skeletal responses play a critical role in disrupting phosphate balance in chronic kidney disease (CKD) patients with mineral and bone disorder (CKD-MBD). In patients with CKD-MBD, the inability of the kidney to maintain normal mineral ion balance affects bone remodeling to induce skeletal fracture and extraskeletal vascular calcification. In physiological conditions, bone-derived fibroblast growth factor 23 (FGF23) acts on the kidney to reduce serum phosphate and 1,25-dihydroxyvitamin D levels. In humans, increased bioactivity of FGF23 leads to increased urinary phosphate excretion, which induces hypophosphatemic diseases (e.g., rickets/osteomalacia). However, reduced FGF23 activity is associated with hyperphosphatemic diseases (e.g., tumoral calcinosis). In patients with CKD, high serum levels of FGF23 fail to reduce serum phosphate levels and lead to numerous complications, including vascular calcification, one of the important determinants of mortality of CKD-MBD patients. Of particular significance, molecular, biochemical and morphological changes in patients with CKD-MBD are mostly due to osteo-renal dysregulation of mineral ion metabolism. Furthermore, hyperphosphatemia can partly contribute to the development of secondary hyperparathyroidism in patients with CKD-MBD. Relatively new pharmacological agents including sevelamer hydrochloride, calcitriol analogs and cinacalcet hydrochloride are used either alone, or in combination, to minimize hyperphosphatemia and hyperparathyroidism associated complications to improve morbidity and mortality of CKD-MBD patients. This article will briefly summarize how osteo-renal miscommunication can induce phosphate toxicity, resulting in extensive tissue injuries. Copyright © 2011 Wiley Periodicals, Inc.

Diagnostic and management dilemma of a pancreas-kidney transplant recipient with aplastic anaemia.

PubMed

Viecelli, Andrea; Hessamodini, Hannah; Augustson, Bradley; Lim, Wai Hon

2014-09-25

We report a case of a 57-year-old woman with type I diabetes who had received a simultaneous pancreas-kidney (SPK) transplant maintained on tacrolimus, mycophenolic acid (MPA) and prednisolone. Her renal allograft failed 6 years post-transplant but she continued to have a normal functioning pancreatic allograft. Over the course of 5 years, she developed progressive bone marrow failure with repeat bone marrow aspirates demonstrating an evolution from erythroid hypoplasia to hypocellular marrow and eventual aplastic anaemia despite discontinuation of MPA and reduction of tacrolimus. She was transfusion-dependent and had frequent admissions for sepsis. Despite treatment with antithymocyte globulin and cyclosporine for aplastic anaemia, she developed fatal invasive pulmonary aspergillosis within 3 weeks of treatment. Even though the cause of aplastic anaemia is likely multifactorial, this case highlights the difficulty in balancing the need for versus the risk of ongoing immunosuppression in a SPK transplant recipient who continues to have normal pancreatic graft function. 2014 BMJ Publishing Group Ltd.

Expression of extracellular calcium (Ca2+o)-sensing receptor in human peripheral blood monocytes

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Olozak, I.; Chattopadhyay, N.; Butters, R. R.; Kifor, O.; Scadden, D. T.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

1998-01-01

The calcium-sensing receptor (CaR) is a G protein-coupled receptor playing key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone resorption during bone turnover and may play a role in the "reversal" phase of skeletal remodeling that follows osteoclastic resorption and precedes osteoblastic bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for such mononuclear cells present locally within the bone marrow microenvironment. Indeed, previous studies by other investigators have shown that raising Ca2+o either in vivo or in vitro stimulated the release of interleukin-6 (IL-6) from human peripheral blood monocytes, suggesting that these cells express a Ca2+o-sensing mechanism. In these earlier studies, however, the use of reverse transcription-polymerase chain reaction (RT-PCR) failed to detect transcripts for the CaR previously cloned from parathyroid and kidney in peripheral blood monocytes. Since we recently found that non-specific esterase-positive, putative monocytes isolated from murine bone marrow express the CaR, we reevaluated the expression of this receptor in human peripheral blood monocytes. Immunocytochemistry, flow cytometry, and Western blot analysis, performed using a polyclonal antiserum specific for the CaR, detected CaR protein in human monocytes. In addition, the use of RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products, identified CaR transcripts in the cells. Therefore, taken together, our data show that human peripheral blood monocytes possess both CaR protein and mRNA very similar if not identical to those expressed in parathyroid and kidney that could mediate the previously described, direct effects of Ca2+o on these cells. Furthermore, since mononuclear cells isolated from bone marrow also express the CaR, the latter might play some role in the "reversal" phase of bone remodeling, sensing local changes in Ca2+o resulting from osteoclastic bone resorption and secreting osteotropic cytokines or performing other Ca2+o-regulated functions that contribute to the control of bone turnover.

Optimization of Bone Health in Children before and after Renal Transplantation: Current Perspectives and Future Directions

PubMed Central

Sgambat, Kristen; Moudgil, Asha

2014-01-01

The accrual of healthy bone during the critical period of childhood and adolescence sets the stage for lifelong skeletal health. However, in children with chronic kidney disease (CKD), disturbances in mineral metabolism and endocrine homeostasis begin early on, leading to alterations in bone turnover, mineralization, and volume, and impairing growth. Risk factors for CKD–mineral and bone disorder (CKD–MBD) include nutritional vitamin D deficiency, secondary hyperparathyroidism, increased fibroblast growth factor 23 (FGF-23), altered growth hormone and insulin-like growth factor-1 axis, delayed puberty, malnutrition, and metabolic acidosis. After kidney transplantation, nutritional vitamin D deficiency, persistent hyperparathyroidism, tertiary FGF-23 excess, hypophosphatemia, hypomagnesemia, immunosuppressive therapy, and alteration of sex hormones continue to impair bone health and growth. As function of the renal allograft declines over time, CKD–MBD associated changes are reactivated, further impairing bone health. Strategies to optimize bone health post-transplant include healthy diet, weight-bearing exercise, correction of vitamin D deficiency and acidosis, electrolyte abnormalities, steroid avoidance, and consideration of recombinant human growth hormone therapy. Other drug therapies have been used in adult transplant recipients, but there is insufficient evidence for use in the pediatric population at the present time. Future therapies to be explored include anti-FGF-23 antibodies, FGF-23 receptor blockers, and treatments targeting the colonic microbiota by reduction of generation of bacterial toxins and adsorption of toxic end products that affect bone mineralization. PMID:24605319

Fructus ligustri lucidi ethanol extract improves bone mineral density and properties through modulating calcium absorption-related gene expression in kidney and duodenum of growing rats.

PubMed

Feng, Xin; Lyu, Ying; Wu, Zhenghao; Fang, Yuehui; Xu, Hao; Zhao, Pengling; Xu, Yajun; Feng, Haotian

2014-04-01

Optimizing peak bone mass in early life is one of key preventive strategies against osteoporosis. Fructus ligustri lucidi (FLL), the fruit of Ligustrum lucidum Ait., is a commonly prescribed herb in many kidney-tonifying traditional Chinese medicinal formulas to alleviate osteoporosis. Previously, FLL extracts have been shown to have osteoprotective effect in aged or ovariectomized rats. In the present study, we investigated the effects of FLL ethanol extract on bone mineral density (BMD) and mechanical properties in growing male rats and explored the underlying mechanisms. Male weaning Sprague-Dawley rats were randomized into four groups and orally administrated for 4 months an AIN-93G formula-based diet supplementing with different doses of FLL ethanol extract (0.40, 0.65, and 0.90 %) or vehicle control, respectively. Then calcium balance, serum level of Ca, P, 25(OH)2D3, 1,25(OH)2D3, osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTX-I), and parathyroid hormone, bone microarchitecture, and calcium absorption-related genes expression in duodenum and kidney were analyzed. The results demonstrated that FLL ethanol extract increased BMD of growing rats and improved their bone microarchitecture and mechanical properties. FLL ethanol extract altered bone turnover, as evidenced by increasing a bone formation maker, OCN, and decreasing a bone resorption maker, CTX-I. Intriguingly, both Ca absorption and Ca retention rate were elevated by FLL ethanol extract treatment, possibly through the mechanisms of up-regulating the transcriptions of calcitropic genes in kidney (1α-hydroxylase) and duodenum (vitamin D receptor, calcium transporter calbindin-D9k, and transient receptor potential vanilloid 6). In conclusion, FLL ethanol extract increased bone mass gain and improved bone properties via modulating bone turnover and up-regulating calcium absorption-related gene expression in kidney and duodenum, which could then activate 1,25(OH)2D3-dependent calcium transport in male growing rats.

Increasing Dietary Phosphorus Intake from Food Additives: Potential for Negative Impact on Bone Health123

PubMed Central

Takeda, Eiji; Yamamoto, Hironori; Yamanaka-Okumura, Hisami; Taketani, Yutaka

2014-01-01

It is important to consider whether habitual high phosphorus intake adversely affects bone health, because phosphorus intake has been increasing, whereas calcium intake has been decreasing in dietary patterns. A higher total habitual dietary phosphorus intake has been associated with higher serum parathyroid hormone (PTH) and lower serum calcium concentrations in healthy individuals. Higher serum PTH concentrations have been shown in those who consume foods with phosphorus additives. These findings suggest that long-term dietary phosphorus loads and long-term hyperphosphatemia may have important negative effects on bone health. In contrast, PTH concentrations did not increase as a result of high dietary phosphorus intake when phosphorus was provided with adequate amounts of calcium. Intake of foods with a ratio of calcium to phosphorus close to that found in dairy products led to positive effects on bone health. Several randomized controlled trials have shown positive relations between dairy intake and bone mineral density. In our loading test with a low-calcium, high-phosphorus lunch provided to healthy young men, serum PTH concentrations showed peaks at 1 and 6 h, and serum fibroblast growth factor 23 (FGF23) concentrations increased significantly at 8 h after the meal. In contrast, the high-calcium, high-phosphorus meal suppressed the second PTH and FGF23 elevations until 8 h after the meal. This implies that adequate dietary calcium intake is needed to overcome the interfering effects of high phosphorus intake on PTH and FGF23 secretion. FGF23 acts on the parathyroid gland to decrease PTH mRNA and PTH secretion in rats with normal kidney function. However, increased serum FGF23 is an early alteration of mineral metabolism in chronic kidney disease, causing secondary hyperthyroidism, and implying resistance of the parathyroid gland to the action of FGF23 in chronic kidney disease. These findings suggest that long-term high-phosphorus diets may impair bone health mediated by FGF23 resistance both in chronic kidney disease patients and in the healthy population. PMID:24425727

Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

PubMed Central

Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

2014-01-01

Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

The impact of peripheral serotonin on leptin-brain serotonin axis, bone metabolism and strength in growing rats with experimental chronic kidney disease.

PubMed

Pawlak, Dariusz; Domaniewski, Tomasz; Znorko, Beata; Oksztulska-Kolanek, Ewa; Lipowicz, Paweł; Doroszko, Michał; Karbowska, Malgorzata; Pawlak, Krystyna

2017-12-01

Chronic kidney disease (CKD) results in decreased bone strength. Serotonin (5-HT) is one of the critical regulators of bone health, fulfilling distinct functions depending on its synthesis site: brain-derived serotonin (BDS) favors osteoblast proliferation, whereas gut-derived serotonin (GDS) inhibits it. We assessed the role of BDS and peripheral leptin in the regulation of bone metabolism and strength in young rats with 5/6 nephrectomy. BDS synthesis was accelerated during CKD progression. Decreased peripheral leptin in CKD rats was inversely related to BDS content in the hypothalamus, brainstem and frontal cortex. Serotonin in these brain regions affected bone strength and metabolism in the studied animals. The direct effect of circulating leptin on bone was not shown in uremia. At the molecular level, there was an inverse association between elevated GDS and the expression of cAMP responsive element-binding protein (Creb) gene in bone of CKD animals. In contrast, increased expression of activating transcription factor 4 (Atf4) was shown, which was associated with GDS-dependent transcription factor 1 (Foxo1), clock gene - Cry-1, cell cycle genes: c-Myc, cyclins, and osteoblast differentiation genes. These results identified a previously unknown molecular pathway, by which elevated GDS can shift in Foxo1 target genes from Creb to Atf4-dependent response, disrupting the leptin-BDS - dependent gene pathway in the bone of uremic rats. Thus, in the condition of CKD the effect of BDS and GDS on bone metabolism and strength can't be distinguished. Copyright © 2017 Elsevier Inc. All rights reserved.

Calcium metabolism in health and disease.

PubMed

Peacock, Munro

2010-01-01

This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

Exacerbation of acute kidney injury by bone marrow stromal cells from rats with persistent renin-angiotensin system activation.

PubMed

Kankuri, Esko; Mervaala, Elina E; Storvik, Markus; Ahola, Aija M J; Levijoki, Jouko; Müller, Dominik N; Finckenberg, Piet; Mervaala, Eero M

2015-06-01

Hypertension and persistent activation of the renin-angiotensin system (RAS) are predisposing factors for the development of acute kidney injury (AKI). Although bone-marrow-derived stromal cells (BMSCs) have shown therapeutic promise in treatment of AKI, the impact of pathological RAS on BMSC functionality has remained unresolved. RAS and its local components in the bone marrow are involved in several key steps of cell maturation processes. This may also render the BMSC population vulnerable to alterations even in the early phases of RAS pathology. We isolated transgenic BMSCs (TG-BMSCs) from young end-organ-disease-free rats with increased RAS activation [human angiotensinogen/renin double transgenic rats (dTGRs)] that eventually develop hypertension and die of end-organ damage and kidney failure at 8 weeks of age. Control cells (SD-BMSCs) were isolated from wild-type Sprague-Dawley rats. Cell phenotype, mitochondrial reactive oxygen species (ROS) production and respiration were assessed, and gene expression profiling was carried out using microarrays. Cells' therapeutic efficacy was evaluated in a rat model of acute ischaemia/reperfusion-induced AKI. Serum urea and creatinine were measured at 24 h and 48 h. Acute tubular damage was scored and immunohistochemistry was used for evaluation for markers of inflammation [monocyte chemoattractant protein (MCP-1), ED-1], and kidney injury [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL)]. TG-BMSCs showed distinct mitochondrial morphology, decreased cell respiration and increased production of ROS. Gene expression profiling revealed a pronounced pro-inflammatory phenotype. In contrast with the therapeutic effect of SD-BMSCs, administration of TG-BMSCs in the AKI model resulted in exacerbation of kidney injury and high mortality. Our results demonstrate that early persistent RAS activation can dramatically compromise therapeutic potential of BMSCs by causing a shift into a pro-inflammatory phenotype with mitochondrial dysfunction.

NLRC5 deficiency protects against acute kidney injury in mice by mediating carcinoembryonic antigen-related cell adhesion molecule 1 signaling.

PubMed

Li, Quanxin; Wang, Ziying; Zhang, Yan; Zhu, Jiaqing; Li, Liang; Wang, Xiaojie; Cui, Xiaoyang; Sun, Yu; Tang, Wei; Gao, Chengjiang; Ma, Chunhong; Yi, Fan

2018-06-12

There is significant progress in understanding the structure and function of NLRC5, a member of the nucleotide oligomerization domain-like receptor family. However, in the context of MHC class I gene expression, the functions of NLRC5 in innate and adaptive immune responses beyond the regulation of MHC class I genes remain controversial and unresolved. In particular, the role of NLRC5 in the kidney is unknown. NLRC5 was significantly upregulated in the kidney from mice with renal ischemia/reperfusion injury. NLRC5 deficient mice significantly ameliorated renal injury as evidenced by decreased serum creatinine levels, improved morphological injuries, and reduced inflammatory responses versus wild type mice. Similar protective effects were also observed in cisplatin-induced acute kidney injury. Mechanistically, NLRC5 contributed to renal injury by promoting tubular epithelial cell apoptosis and reducing inflammatory responses were, at least in part, associated with the negative regulation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). To determine the relative contribution of NLRC5 expression by parenchymal cells or leukocytes to renal damage during ischemia/reperfusion injury, we generated bone marrow chimeric mice. NLRC5 deficient mice engrafted with wild type hematopoietic cells had significantly lower serum creatinine and less tubular damage than wild type mice reconstituted with NLRC5 deficient bone marrow. This suggests that NLRC5 signaling in renal parenchymal cells plays the dominant role in mediating renal damage. Thus, modulation of the NLRC5-mediated pathway may have important therapeutic implications for patients with acute kidney injury. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Mineral & Bone Disorder in Chronic Kidney Disease

MedlinePlus

... Kidney Disease Anemia in Chronic Kidney Disease Financial Help for Treatment of Kidney Failure Learning as much as you can about your treatment will help make you an important member of your health ...

Long-term accumulation of uranium in bones of Wistar rats as a function of intake dosages.

PubMed

Arruda-Neto, J D T; Guevara, M V Manso; Nogueira, G P; Saiki, M; Cestari, A C; Shtejer, K; Deppman, A; Pereira Filho, J W; Garcia, F; Geraldo, L P; Gouveia, A N; Guzmán, F; Mesa, J; Rodriguez, O; Semmler, R; Vanin, V R

2004-01-01

Groups of Wistar rats were fed with ration doped with uranyl nitrate at concentration A ranging from 0.5 to 100 ppm, starting after the weaning period and lasting until the postpuberty period when the animals were sacrificed. Uranium in the ashes of bones was determined by neutron activation analysis. It was found that the uranium concentration in the bones, as a function of A, exhibits a change in its slope at approximately 20 ppm-a probable consequence of the malfunctioning of kidneys. The uranium transfer coefficient was obtained and an analytical expression was fitted into the data, thus allowing extrapolation down to low doses. Internal and localized doses were calculated. Absorbed doses exceeded the critical dose, even for the lowest uranium dosage.

Stem Cell Mobilizers: Novel Therapeutics for Acute Kidney Injury.

PubMed

Xu, Yue; Zeng, Song; Zhang, Qiang; Zhang, Zijian; Hu, Xiaopeng

2017-01-01

In the past decade, rapid developments in stem cell studies have occurred. Researchers have confirmed the plasticity of bone marrow stem cells and the repair and regeneration effects of bone marrow hematopoietic stem cells on solid organs. These findings have suggested the possibility of using bone marrow stem cell mobilizers to repair and regenerate injured organs. Recent studies on the effects of granulocyte colony-stimulating factor (G-CSF) and Plerixafor (AMD3100) on mouse acute kidney injury models have confirmed that the use of bone marrow stem cell mobilizers may be an effective therapeutic measure. This paper summarizes studies describing the effects of G-CSF and AMD3100 on various acute kidney injury models over the past 10 years. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Leukemia kidney infiltration can cause secondary polycythemia by activating hypoxia-inducible factor (HIF) pathway.

PubMed

Osumi, Tomoo; Awazu, Midori; Fujimura, Eriko; Yamazaki, Fumito; Hashiguchi, Akinori; Shimada, Hiroyuki

2013-06-01

Secondary polycythemia with increased production of erythropoietin (EPO) is known to occur in kidney diseases such as hydronephrosis and cystic disease, but the mechanism remains unclear. We report an 18-year-old female with isolated renal relapse of acute lymphoblastic leukemia accompanied by polycythemia. At the relapse, she presented with bilateral nephromegaly, mild renal dysfunction, and erythrocytosis with increased serum EPO levels up to 52.1 mIU/mL (9.1-32.8). Renal biopsy demonstrated diffuse lymphoblastic infiltration. The expression of hypoxia-inducible factor (HIF)-1α, which is undetectable in normal kidney, was observed in the renal tubule epithelium compressed by lymphoblastic cells. These findings suggest that erythrocytosis was caused by renal ischemia due to leukemic infiltration. Polycythemia probably became apparent because of the lack of leukemic involvement of the bone marrow. With chemotherapy, the serum EPO level rapidly decreased to normal range accompanied by the normalization of kidney size and function. Renal leukemic infiltration may enhance EPO production, although not recognized in the majority of cases because of bone marrow involvement. Our case has clarified the mechanism of previously reported polycythemia associated with renal diseases as renal ischemia. Furthermore, we have added renal ischemia resulting from tumor infiltration to the list of causes of secondary polycythemia.

The Effect of Diet on the Survival of Patients with Chronic Kidney Disease

PubMed Central

Rysz, Jacek; Franczyk, Beata; Ciałkowska-Rysz, Aleksandra; Gluba-Brzózka, Anna

2017-01-01

The prevalence of chronic kidney disease (CKD) is high and it is gradually increasing. Individuals with CKD should introduce appropriate measures to hamper the progression of kidney function deterioration as well as prevent the development or progression of CKD-related diseases. A kidney-friendly diet may help to protect kidneys from further damage. Patients with kidney damage should limit the intake of certain foods to reduce the accumulation of unexcreted metabolic products and also to protect against hypertension, proteinuria and other heart and bone health problems. Despite the fact that the influence of certain types of nutrients has been widely studied in relation to kidney function and overall health in CKD patients, there are few studies on the impact of a specific diet on their survival. Animal studies demonstrated prolonged survival of rats with CKD fed with protein-restricted diets. In humans, the results of studies are conflicting. Some of them indicate slowing down of the progression of kidney disease and reduction in proteinuria, but other underline significant worsening of patients’ nutritional state, which can be dangerous. A recent systemic study revealed that a healthy diet comprising many fruits and vegetables, fish, legumes, whole grains, and fibers and also the cutting down on red meat, sodium, and refined sugar intake was associated with lower mortality in people with kidney disease. The aim of this paper is to review the results of studies concerning the impact of diet on the survival of CKD patients. PMID:28505087

The Effect of Diet on the Survival of Patients with Chronic Kidney Disease.

PubMed

Rysz, Jacek; Franczyk, Beata; Ciałkowska-Rysz, Aleksandra; Gluba-Brzózka, Anna

2017-05-13

The prevalence of chronic kidney disease (CKD) is high and it is gradually increasing. Individuals with CKD should introduce appropriate measures to hamper the progression of kidney function deterioration as well as prevent the development or progression of CKD-related diseases. A kidney-friendly diet may help to protect kidneys from further damage. Patients with kidney damage should limit the intake of certain foods to reduce the accumulation of unexcreted metabolic products and also to protect against hypertension, proteinuria and other heart and bone health problems. Despite the fact that the influence of certain types of nutrients has been widely studied in relation to kidney function and overall health in CKD patients, there are few studies on the impact of a specific diet on their survival. Animal studies demonstrated prolonged survival of rats with CKD fed with protein-restricted diets. In humans, the results of studies are conflicting. Some of them indicate slowing down of the progression of kidney disease and reduction in proteinuria, but other underline significant worsening of patients' nutritional state, which can be dangerous. A recent systemic study revealed that a healthy diet comprising many fruits and vegetables, fish, legumes, whole grains, and fibers and also the cutting down on red meat, sodium, and refined sugar intake was associated with lower mortality in people with kidney disease. The aim of this paper is to review the results of studies concerning the impact of diet on the survival of CKD patients.

Alkaline Diet and Metabolic Acidosis: Practical Approaches to the Nutritional Management of Chronic Kidney Disease.

PubMed

Rodrigues Neto Angéloco, Larissa; Arces de Souza, Gabriela Cristina; Almeida Romão, Elen; Garcia Chiarello, Paula

2018-05-01

The kidneys play an extremely important role in maintaining the body acid-base balance by excreting nonvolatile acids and regenerating and reabsorbing bicarbonate in the kidney tubules. As the individual loses their kidney function, renal excretion of nonvolatile acid produced by metabolism of the diet is impaired, resulting in low-grade metabolic acidosis. With this in mind, it is relevant to better understand the dietary aspects related to the acid-base balance in chronic kidney disease metabolic acidosis and try to provide possible strategies for the nutritional management of these cases. The type of diet can deeply affect the body by providing acid or base precursors. Generally speaking, foods such as meat, eggs, cheese, and grains increase the production of acid in the organism, whereas fruit and vegetables are alkalizing. On the other hand, milk is considered neutral as well as fats and sugars, which have a small effect on acid-base balance. The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products. Thus metabolic acidosis may be exacerbated by a contemporary Western diet, which delivers a high nonvolatile acid load. The remaining acid is neutralized or stored within the body. Bone and muscle are lost to neutralize the acid and serum bicarbonate falls. Early studies suggest that lowering the dietary acid load with a reduced protein content and vegetable proteins replacements, associated with an increase in fruits and vegetables intake can improve the metabolic parameters of acidosis, preserve bone and muscle, and slow the glomerular filtration rate decline. More studies focusing on the effects of controlled dietary interventions among chronic kidney disease patients are needed to determining the optimal target for nutritional therapy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Kidney tissue targeted metabolic profiling of glucocorticoid-induced osteoporosis and the proposed therapeutic effects of Rhizoma Drynariae studied using UHPLC/MS/MS.

PubMed

Huang, Yue; Liu, Xinyu; Zhao, Longshan; Li, Famei; Xiong, Zhili

2014-06-01

Traditional Chinese medicine and modern science have indicated that there is a close relationship between bone and kidney. In light of this, this project was designed to study the metabolic profiling by UHPLC/MS/MS of glucocorticoid-induced osteoporosis in kidney tissue and the possible therapeutic effects of Rhizoma Drynariae (RD), a classic traditional Chinese medicine, in improving the kidney function and strengthening bone. Twenty-one Wistar rats were divided into three groups: control group (rats before prednisolone inducing), a model group (prednisolone-induced group) and a treatment group (prednisolone-induced rats that were then administered RD ethanol extracts). By using pattern recognition analysis, a significant change in the metabolic profile of kidney tissue samples was observed in the model group and restoration of the profile was observed after the administration of RD ethanol extracts. Some significantly changed biomarkers related to osteoporosis such as sphingolipids (C16 dihydrosphingosine, C18 dihydrosphingosine, C18 phytosphingosine, C20 phytosphingosine), lysophosphatidycholines (C16:0 LPC, C18:0 LPC) and phenylalanine were identified. As a complement to the metabolic profiling of RD in plasma, these biomarkers suggest that kidney damage, cell cytotoxicity and apoptosis exist in osteoporosis rats, which is helpful in further understanding the underlying process of glucocorticoid-induced osetoporosis and the suggested therapeutic effects of RD. The method shows that tissue target metabonomics might provide a powerful tool to further understand the process of disease and the mechanism of therapeutic effect of Chinese medicines. Copyright © 2014 John Wiley & Sons, Ltd.

Evaluating bone quality in patients with chronic kidney disease

PubMed Central

Malluche, Hartmut H.; Porter, Daniel S.; Pienkowski, David

2013-01-01

Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease–mineral and bone disorder (CKD–MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD–MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD–MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD–MBD should aid in the development of new modalities to prevent, or treat, these abnormalities. PMID:24100399

Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone

PubMed Central

Culbertson, Christopher D.; Kyker-Snowman, Kelly; Bushinsky, David A.

2012-01-01

Fibroblast growth factor 23 (FGF23) significantly increases with declining renal function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25-dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the mechanisms by which it is regulated are not clear. Patients with chronic kidney disease have decreased renal acid excretion leading to metabolic acidosis, which has a direct effect on bone cell activity. We hypothesized that metabolic acidosis would directly increase bone cell FGF23 production. Using cultured neonatal mouse calvariae, we found that metabolic acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at 24 h and 48 h compared with incubation in neutral pH medium. To exclude that the increased FGF23 was secondary to metabolic acidosis-induced release of bone mineral phosphate, we cultured primary calvarial osteoblasts. In these cells, metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and protein in mouse bone. If these results are confirmed in humans with chronic kidney disease, therapeutic interventions to mitigate acidosis, such as bicarbonate administration, may also lower levels of FGF23, decrease left ventricular hypertrophy, and perhaps even decrease mortality. PMID:22647635

Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair.

PubMed

Ahmed, Hanaa H; Toson, Elshahat A; El-Mezayen, Hatem A; Rashed, Laila A; Elsherbiny, Eslam S

2017-07-01

The current study sought to clarify the role of bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived mesenchymal stem cells (AD-MSCs) in repressing nephropathy in the experimental model. Moreover, the aim of this work was extended to compare between stem cells role and angiotensin converting enzyme inhibitor in kidney repair. Isolation and preparation of MSCs culture, flow cytometry using CD34, CD44 and CD105 cell surface markers, biochemical analyses for determination of serum creatinine, urea, transforming growth factor β (TGF-β), cystatin C (CYS-C) and urinary N-Acetyl-ß-D-Glucosaminidase (UNAG), and histopathological investigation of kidney tissue sections were performed. The results of the present study revealed that single intravenous infusion of MSCs either derived from bone marrow or adipose tissue was able to enhance renal reparative processes through significantly decreased serum creatinine, urea, TGF-β and CYS-C levels as well as UNAG level and significantly increase glomerular filtration rate. Additionally, the histopathological investigations of kidney tissues showed that MSCs have significant regenerative effects as evidenced by the decrease in focal inflammatory cells infiltration, focal interstitial nephritis and congested glomeruli as well as degenerated tubules. The current data provided distinct evidence about the favourable impact of AD-MSCs and BM-MSCs in attenuation of cyclosporine-induced nephropathy in rats through their ability to promote functional and structural kidney repair via transdifferentiation. © 2016 Asian Pacific Society of Nephrology.

Chronic kidney disease-mineral and bone disorder: Guidelines for diagnosis, treatment, and management.

PubMed

Moschella, Carla

2016-07-01

Chronic kidney disease affects 23 million Americans and is associated with many complications, one of the most complex of which is mineral and bone disorder. Pathophysiologic mechanisms begin to occur early in CKD but when the glomerular filtration rate declines to <50% of normal, biochemical and bone matrix abnormalities, which vary and are multifactorial, begin to be clinically apparent. Mainstays of treatment remain management of hyperphosphatemia and prevention or treatment of secondary hyperparathyroidism.

Acute radiation nephritis. Its evolution on sequential bone imaging

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

Palestro, C.; Fineman, D.; Goldsmith, S.J.

1988-11-01

Acute radiation nephritis typically affects the kidneys 3-12 months after radiation exposure and may occur with doses as low as 2500 rads. After an initial latent period, the affected portions of the kidneys become swollen and edematous, and develop multiple petechiae. Necrotizing vasculitis and interstitial hemorrhage occur, and the end stage is that of scarring. Two patients are presented in whom localized acute radiation nephritis developed, and whose kidneys demonstrated the characteristic sequential changes of this entity on serial bone imaging.

Kidney transplantation restored uncoupled bone turnover in end-stage renal disease.

PubMed

Kawarazaki, Hiroo; Shibagaki, Yugo; Kido, Ryo; Nakajima, Ichiro; Fuchinoue, Shohei; Ando, Katsuyuki; Fujita, Toshiro; Fukagawa, Masafumi; Teraoka, Satoshi; Fukumoto, Seiji

2012-07-01

While kidney transplantation (KTx) reverses many disorders associated with end-stage renal disease (ESRD), patients who have received KTx often have chronic kidney disease and bone and mineral disorder (CKD-MBD). However, it is unknown how bone metabolism changes by KTx. Living donor-KTx recipients (n = 34) at Tokyo Women's Medical University were prospectively recruited and the levels of bone-specific alkaline phosphatase (BAP) and serum cross-linked N-telopeptides of Type 1 collagen (NTX) were measured before, 6 and 12 months after transplantation. Before KTx, serum BAP was within the reference range in more than half of patients while NTX was high in most patients. Serum NTX was higher in patients with longer dialysis durations compared to that with shorter durations before KTx. However, there was no difference in serum BAP between these patients. After KTx, BAP increased while NTX decreased along with the decline of PTH. In addition, the numbers of patients who showed high BAP and NTX were comparable after KTx. These results suggest that bone formation is suppressed and uncoupled with bone resorption in patients with ESRD and this uncoupling is restored by KTx. Further studies are necessary to clarify the mechanism of bone uncoupling in patients with ESRD.

Anemia in Chronic Kidney Disease

MedlinePlus

... Heart Disease Mineral & Bone Disorder Anemia in Chronic Kidney Disease What is anemia? Anemia is a condition ... they should. How is anemia related to chronic kidney disease? Anemia commonly occurs in people with chronic ...

Dietary Changes Involving Bifidobacterium longum and Other Nutrients Delays Chronic Kidney Disease Progression.

PubMed

Iwashita, Yuko; Ohya, Masaki; Yashiro, Mitsuru; Sonou, Tomohiro; Kawakami, Kazuki; Nakashima, Yuri; Yano, Takuro; Iwashita, Yu; Mima, Toru; Negi, Shigeo; Kubo, Kaoru; Tomoda, Koichi; Odamaki, Toshitaka; Shigematsu, Takashi

2018-01-01

Recent studies suggest that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment. However, the gut microbiota and kidney disease interactions remain to be determined. This study investigated whether synbiotics modulate the gut microbiota and ameliorate kidney function using a rat model of chronic kidney disease (CKD). As uremic toxins are associated with CKD-related mineral and bone disorder, the secondary aim was to evaluate the relationship between synbiotics and secondary hyperparathyroidism (SHPT). 5/6 nephrectomy (Nx) rats were developed as the CKD model. Sham-operated (sham) rats were used as the control. To investigate the effectiveness of prebiotics (glutamine, dietary fiber, and oligosaccharide) and probiotics (Bifidobacterium longum strain; GFOB diet), rats were randomly assigned to 4 groups: Nx group fed the GFOB diet (n = 10); Nx group fed the control (CON) diet (n = 10); sham group fed the GFOB diet (n = 5); and sham group fed the control diet (n = 5). Blood, feces, and kidney samples were collected and analyzed. Serum creatinine (Cre) and blood urea nitrogen in the Nx GFOB group were significantly lower than those in the Nx CON group. Serum indoxyl sulfate in the Nx GFOB group was lower than that in the Nx CON group, and significantly correlated with serum Cre. Inorganic phosphorus and intact parathyroid hormone in the Nx GFOB group were significantly lower than those in the Nx CON group. Improving the gut environment using synbiotics ameliorated kidney function and might be a pharmacological treatment for SHPT without any serious adverse events. © 2018 S. Karger AG, Basel.

HILDA/LIF urinary excretion during acute kidney rejection.

PubMed

Taupin, J L; Morel, D; Moreau, J F; Gualde, N; Potaux, L; Bezian, J H

1992-03-01

Recently, a new lymphokine called HILDA (human interleukin for DA cells) has been described and cloned. This cytokine, initially described to be produced by alloreactive T lymphocyte clones grown from a rejected human kidney allograft, is identical to other factors termed D-factor, differentiation-inducing factor, differentiation inhibitory activity, hepatocyte-stimulating factor III, and leukemia inhibitory factor. HILDA/LIF induces various effects on neural, hemopoietic, embryonic cells as well as on bone remodeling and acute phase protein synthesis in hepatocyte. In this study we demonstrate the presence of HILDA/LIF in the urine but not in the serum of kidney graft recipients during acute rejection episodes, whereas this lymphokine was detectable neither in the serum nor in the urine of kidney transplanted patients with stable renal function. These data reinforce the notion of a possible role for this lymphokine in the inflammatory and/or the immune response.

High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease.

PubMed

Lau, Wei Ling; Linnes, Michael; Chu, Emily Y; Foster, Brian L; Bartley, Bryan A; Somerman, Martha J; Giachelli, Cecilia M

2013-01-01

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic syndrome characterized by imbalances in mineral homeostasis, renal osteodystrophy (ROD) and ectopic calcification. The mechanisms underlying this syndrome in individuals with chronic kidney disease (CKD) are not yet clear. We examined the effect of normal phosphate (NP) or high phosphate (HP) feeding in the setting of CKD on bone pathology, serum biochemistry and vascular calcification in calcification-prone dilute brown non-agouti (DBA/2) mice. In both NP and HP-fed CKD mice, elevated serum parathyroid hormone and alkaline phosphatase (ALP) levels were observed, but serum phosphorus levels were equivalent compared with sham controls. CKD mice on NP diet showed trabecular alterations in the long bone consistent with high-turnover ROD, including increased trabecular number with abundant osteoblasts and osteoclasts. Despite trabecular bone and serum biochemical changes, CKD/NP mice did not develop vascular calcification. In contrast, CKD/HP mice developed arterial medial calcification (AMC), more severe trabecular bone alterations and cortical bone abnormalities that included decreased cortical thickness and density, and increased cortical porosity. Cortical bone porosity and trabecular number strongly correlated with the degree of aortic calcification. HP feeding was required to induce the full spectrum of CKD-MBD symptoms in CKD mice.

Effect of Twice-Yearly Denosumab on Prevention of Bone Mineral Density Loss in De Novo Kidney Transplant Recipients: A Randomized Controlled Trial.

PubMed

Bonani, M; Frey, D; Brockmann, J; Fehr, T; Mueller, T F; Saleh, L; von Eckardstein, A; Graf, N; Wüthrich, R P

2016-06-01

We conducted an open-label, prospective, randomized trial to assess the efficacy and safety of RANKL inhibition with denosumab to prevent the loss of bone mineral density (BMD) in the first year after kidney transplantation. Ninety kidney transplant recipients were randomized 1:1 2 weeks after surgery to receive denosumab (60 mg at baseline and 6 months) or no treatment. After 12 months, total lumbar spine areal BMD (aBMD) increased by 4.6% (95% confidence interval [CI] 3.3-5.9%) in 46 patients in the denosumab group and decreased by -0.5% (95% CI -1.8% to 0.9%) in 44 patients in the control group (between-group difference 5.1% [95% CI 3.1-7.0%], p < 0.0001). Denosumab also increased aBMD at the total hip by 1.9% (95% CI, 0.1-3.7%; p = 0.035) over that in the control group at 12 months. High-resolution peripheral quantitative computed tomography in a subgroup of 24 patients showed that denosumab increased volumetric BMD at the distal tibia and radius (all p < 0.05). Biomarkers of bone turnover (C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide) markedly decreased with denosumab (all p < 0.0001). Episodes of cystitis and asymptomatic hypocalcemia occurred more often with denosumab, whereas graft function, rate of rejections, and incidence of opportunistic infections were similar. In conclusion, denosumab increased BMD in the first year after kidney transplantation but was associated with more frequent episodes of urinary tract infection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

[Regression analysis of serum bone metabolic markers and traditional Chinese medicine syndromes in patients with CKD-MBD].

PubMed

Yang, Hai-Ming; Meng, Xian-Jie; Wu, Wei; Liu, Ying-Lu; Zhai, Xiao-Juan

2017-10-01

To analyze the interdependent relationship between serum bone metabolic markers and traditional Chinese medicine (TCM) syndromes in patients with chronic kidney disease (stages 3 and 4)-related mineral and bone disorder (CKD-MBD), in order to provide the objective basis for exploring the rules of TCM syndrome differentiation in patients with CKD-MBD. The retrospective survey was conducted to collect 105 cases with CKD (stages 3 and 4)-MBD. General clinical indexes, frequency of TCM syndromes and distribution of TCM syndrome type were investigated. Furthermore, serum bone metabolic markers, including calcium (Ca2+), phosphonium (P3+), intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), procollagen type 1 amino-N-terminal propeptide (P1NP) and β-crosslaps (β-CTX) were analyzed, respectively. Meanwhile, bone mineral density (BMD) was assessed. And then, the multivariate regression analysis was performed for serum bone metabolic markers and TCM syndromes. The results showed that the general clinical features of the 105 patients included old age, hypertension, fracture, loss of bone mass and mild abnormalities of serum bone metabolic markers. High-frequency TCM syndromes were related to Yang deficiency in Spleen and Kidney, Qi deficiency in Spleen and Kidney and blood stasis. Moreover, Yang deficiency in Spleen and Kidney and blood stasis were found as the most frequent characteristics of the distribution of TCM syndromes type. The clinical characteristics of patients with the syndrome type of Yang deficiency in Spleen and Kidney were probably old age, increase in TCM syndrome scores and abnormalities in iPTH and P1NP. In addition, the interdependent relationship between abnormality in Ca2+ and syndromes of hair loss, tooth shake and sexual dysfunction, abnormality in P3+ and syndromes of aches in waist and knees, abnormality in iPTH and syndromes of soreness and weakness in waist and knees, lassitude, fatigue and extreme chilliness, abnormality in ALP and syndromes of loose stools, abnormality in P1NP and syndromes of fear of chills, tendency of warmth and loose stools, and abnormality in β-CTX and syndromes of chills and pain in waist and knees. In general, among the 105 cases with CKD (stages 3 and 4)-MBD were clinically characterized by mild changes in serum bone metabolic markers; And their main TCM syndrome was the deficiency in spleen and kidney. Serum bone metabolic markers with mild changes have an interdependent relationship with main TCM syndromes, and can be considered as an objective syndrome factor of TCM syndrome differentiation. Copyright© by the Chinese Pharmaceutical Association.

Multiple Faces of FGF-23

PubMed Central

Han, Xiaobin; Quarles, L. Darryl

2016-01-01

Purpose of the review This review examines therole of FGF-23 in mineral metabolism, innate immunity and adverse cardiovascular outcomes. Recent findings FGF-23, produced by osteocytes in bone, activates FGFR/α-Klotho complexes in the kidney. The resulting bone-kidney axis coordinates renal phosphate reabsorption with bone mineralization, and creates a counter-regulatory feedback loop to prevent vitamin D toxicity. FGF-23 acts to counter-regulate the effects of Vitamin D on innate immunity and cardiovascular responses. FGF-23 is ectopically expressed along with α-Klotho in activated macrophages, creating a pro-inflammatory paracrine signaling pathway that counters the anti-inflammatory actions of vitamin D. FGF-23 also inhibits ACE2 expression and increases sodium reabsorption in the kidney, leading to hypertension and left ventricular hypertrophy. Finally, FGF-23 is purported to cause adverse cardiac and impair neutrophil responses through activation of FGFRs in the absence of α-Klotho. While secreted forms of α-Klotho have FGF-23- independent effects, the possibility of α-Klotho-independent effects of FGF-23 is controversial and requires additional experimental validation. Summary FGF-23 participates in a bone-kidney axis regulating mineral homeostasis, proinflammatory paracrine macrophage signaling pathways, and in a bone-cardio-renal axis regulating hemodynamics that counteract the effects of Vitamin D. PMID:27219044

Multiple faces of fibroblast growth factor-23.

PubMed

Han, Xiaobin; Quarles, L Darryl

2016-07-01

This review examines the role of fibroblast growth factor-23 (FGF-23) in mineral metabolism, innate immunity and adverse cardiovascular outcomes. FGF-23, produced by osteocytes in bone, activates FGFR/α-Klotho (α-Kl) complexes in the kidney. The resulting bone-kidney axis coordinates renal phosphate reabsorption with bone mineralization, and creates a counter-regulatory feedback loop to prevent vitamin D toxicity. FGF-23 acts to counter-regulate the effects of vitamin D on innate immunity and cardiovascular responses. FGF-23 is ectopically expressed along with α-Kl in activated macrophages, creating a proinflammatory paracrine signaling pathway that counters the antiinflammatory actions of vitamin D. FGF-23 also inhibits angiotensin-converting enzyme 2 expression and increases sodium reabsorption in the kidney, leading to hypertension and left ventricular hypertrophy. Finally, FGF-23 is purported to cause adverse cardiac and impair neutrophil responses through activation of FGFRs in the absence of α-Kl. Although secreted forms of α-Kl have FGF-23 independent effects, the possibility of α-Kl independent effects of FGF-23 is controversial and requires additional experimental validation. FGF-23 participates in a bone-kidney axis regulating mineral homeostasis, proinflammatory paracrine macrophage signaling pathways, and in a bone-cardio-renal axis regulating hemodynamics that counteract the effects of vitamin D.

At Risk for Kidney Disease?

MedlinePlus

... in Adults Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Pour les personnes atteintes de diabète ou d’hypertension artérielle Heart Disease Mineral & Bone Disorder Causes of Chronic Kidney ...

Heart failure in patients with kidney disease.

PubMed

Tuegel, Courtney; Bansal, Nisha

2017-12-01

Heart failure (HF) is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), and the population of CKD patients with concurrent HF continues to grow. The accurate diagnosis of HF is challenging in patients with CKD in part due to a lack of validated imaging and biomarkers specifically in this population. The pathophysiology between the heart and the kidneys is complex and bidirectional. Patients with CKD have greater prevalence of traditional HF risk factors as well as unique kidney-specific risk factors including malnutrition, acid-base alterations, uraemic toxins, bone mineral changes, anemia and myocardial stunning. These risk factors also contribute to the decline of kidney function seen in patients with subclinical and clinical HF. More targeted HF therapies may improve outcomes in patients with kidney disease as current HF therapies are underutilised in this population. Further work is also needed to develop novel HF therapies for the CKD population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The role of mineral and bone disorders in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus of long duration.

PubMed

Biragova, Margarita S; Gracheva, Svetlana A; Glazunova, Alexandra M; Martynov, Sergey A; Ulaynova, Irina N; Ilyin, Alexandr V; Philippov, Yury I; Musaeva, Guliya M; Shamkhalova, Minara S; Shestakova, Marina V

2016-08-01

The objective of our study was to evaluate the role of mineral and bone metabolism disorders associated with chronic kidney disease (MBD-CKD) in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus (T1DM) of long duration. We investigated 96 patients with T1DM of long duration, with CKD at different stages (0-5), including patients on hemodialysis (HD) and with kidney transplantation (KT). Along with overall clinical examination, we assessed markers of MBD (calcium, phosphorus, parathormone, vitamin D, fibroblast growth factor (FGF) 23) and levels of cardiac injury marker (atrial natriuretic peptide, NT-proBNP). Multispiral computer tomography with Agatston index calculation was also included. Decreased kidney function was associated with increased of levels phosphorus, parathormone, FGF 23, and vitamin D deficiency, with the highest deviation from the reference ranges seen in patients on HD with a very high risk of cardiovascular events. In KT patients with satisfactory graft function, these parameters were at the same levels as in patients with CKD stages 0-4. Progression of cardiovascular pathology was accompanied by elevation of NT-proBNP levels as CKD duration increased, decreased glomerular filtration rate, and were correlated with the main parameters of mineral homeostasis. The severity of coronary arteries calcification was associated with patient age and duration of T1DM and arterial hypertension. Development and progression of kidney dysfunction is accompanied by MBD, a significant factor in progression of cardiac pathology, which remains a major cause of mortality in this patient population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acid retention with reduced glomerular filtration rate increases urine biomarkers of kidney and bone injury.

PubMed

Wesson, Donald E; Pruszynski, Jessica; Cai, Wendy; Simoni, Jan

2017-04-01

Diets high in acid of developed societies that do not cause metabolic acidosis in patients with chronic kidney disease nevertheless appear to cause acid retention with associated morbidity, particularly in those with reduced glomerular filtration rate. Here we used a rat 2/3 nephrectomy model of chronic kidney disease to study induction and maintenance of acid retention and its consequences on indicators of kidney and bone injury. Dietary acid was increased in animals eating base-producing soy protein with acid-producing casein and in casein-eating animals with added ammonium chloride. Using microdialysis to measure the kidney cortical acid content, we found that nephrectomized animals had greater acid retention than sham-operated animals when both ate the soy diet. Each increment in dietary acid further increased acid retention more in nephrectomized than in sham rats. Nephrectomized and sham animals achieved similar steady-state daily urine net acid excretion in response to increments in dietary acid but nephrectomized animals took longer to do so, contributing to greater acid retention that was maintained until the increased dietary acid was stopped. Acid retention was associated with increased urine excretion of both N-acetyl-β-D-glucosaminidase and deoxypyridinoline, greater in nephrectomized than control rats, consistent with kidney tubulointerstitial and bone matrix injury, respectively. Greater acid retention in nephrectomized than control animals was induced by a slower increase in urinary net acid excretion rate in response to the increment in dietary acid and also maintained until the dietary acid increment was stopped. Thus, acid retention increased biomarkers of kidney and bone injury in the urine, supporting untoward consequences to these two tissues. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Functions of vasopressin and oxytocin in bone mass regulation

PubMed Central

Sun, Li; Tamma, Roberto; Yuen, Tony; Colaianni, Graziana; Ji, Yaoting; Cuscito, Concetta; Bailey, Jack; Dhawan, Samarth; Lu, Ping; Calvano, Cosima D.; Zhu, Ling-Ling; Zambonin, Carlo G.; Di Benedetto, Adriana; Stachnik, Agnes; Liu, Peng; Grano, Maria; Colucci, Silvia; Davies, Terry F.; New, Maria I.; Zallone, Alberta; Zaidi, Mone

2016-01-01

Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr−/− mice have osteopenia, and Avpr1α−/− mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr−/−:Avpr1α−/− double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α−/− cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling. PMID:26699482

Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.

PubMed

Vize, P D; Seufert, D W; Carroll, T J; Wallingford, J B

1997-08-15

Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all forms of the kidney are closely related structures. Given the similarities between the development of simple and complex kidneys, the embryonic kidneys may be an ideal model system in which to investigate the genesis of multicomponent organ systems.

Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone tissue of apolipoprotein-E knockout mice with chronic kidney disease.

PubMed

Barreto, Fellype C; de Oliveira, Rodrigo B; Benchitrit, Joyce; Louvet, Loïc; Rezg, Raja; Poirot, Sabrina; Jorgetti, Vanda; Drüeke, Tilman B; Riser, Bruce L; Massy, Ziad A

2014-11-01

Vascular calcification (VC) is a risk factor for cardiovascular mortality in the setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous molecule that inhibits hydroxyapatite crystal formation, has been shown to prevent the development of VC in animal models of CKD. However, the possibility of harmful effects of exogenous administration of PPi on bone requires further investigation. To this end, we examined by histomorphometry the bone of CKD mice after intraperitoneal PPi administration. After CKD creation or sham surgery, 10-week-old female apolipoprotein-E knockout (apoE(-/-)) mice were randomized to one non-CKD group or 4 CKD groups (n = 10-35/group) treated with placebo or three distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals were killed. Serum and femurs were sampled. Femurs were processed for bone histomorphometry. Placebo-treated CKD mice had significantly higher values of osteoid volume, osteoid surface and bone formation rate than sham-placebo mice with normal renal function. Slightly higher osteoid values were observed in CKD mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD mice. Treatment with PPi did not modify any other structural parameters. Mineral apposition rates, and other parameters of bone formation and resorption were not significantly different among the treated animal groups or control CKD placebo group. In conclusion, PPi does not appear to be deleterious to bone tissue in apoE(-/-) mice with CKD, although a possible stimulatory PPi effect on osteoid formation may be worth further investigation.

BK virus associated pronounced hemorrhagic cystoureteritis after bone marrow transplantation.

PubMed

Haab, Alexander C; Keller, Isabelle S; Padevit, Christian; John, Hubert

2015-10-01

Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of immunodeficiency is very rare. More common is the appearance of a hemorrhagic cystitis. This report not only shows bilateral ureteral stenosis after bone marrow transplantation, but also presents severe complications as chronic pelvic pain and impaired kidney function as well as irreparable damage to the whole urinary tract leading to nephroureterectomy, subtrigonal cystectomy and orthotopic ileal neobladder. Finally renal transplantation was required. To our knowledge this is the first case in the literature where such a severe course of BKV associated hemorrhagic cystoureteritis is described.

Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia.

PubMed

Mace, Maria L; Gravesen, Eva; Nordholm, Anders; Hofman-Bang, Jacob; Secher, Thomas; Olgaard, Klaus; Lewin, Ewa

2017-07-01

Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia. FGF23 mRNA was not detected in normal kidneys, but was clearly demonstrated in injured kidneys, already after four hours in obstructive nephropathy and at 8 weeks in the remnant kidney of 5/6 nephrectomized rats. No renal extraction was found in uremic rats in contrast to normal rats. Removal of the remnant kidney had no effect on plasma FGF23 levels. Well-known regulators of FGF23 expression in bone, such as parathyroid hormone, calcitriol, and inhibition of the FGF receptor by PD173074, had no impact on kidney expression of FGF23. Thus, the only direct contribution of the injured kidney to circulating FGF23 levels in uremia appears to be reduced renal extraction of bone-derived FGF23. Kidney-derived FGF23 does not generate high plasma FGF23 levels in uremia and is regulated differently than the corresponding regulation of FGF23 gene expression in bone. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Evolution of bone disease after kidney transplantation: A prospective histomorphometric analysis of trabecular and cortical bone.

PubMed

Carvalho, Catarina; Magalhães, Juliana; Pereira, Luciano; Simões-Silva, Liliana; Castro-Ferreira, Inês; Frazão, João Miguel

2016-01-01

Post-transplant bone disease results from multiple factors, including previous bone and mineral metabolism disturbances and effects from transplant-related medications. Bone biopsy remains the gold-standard diagnostic tool. We aimed to prospectively evaluate trabecular and cortical bone by histomorphometry after kidney transplantation. Seven patients, willing to perform follow-up bone biopsy, were included in the study. Dual-X-ray absorptiometry and trans-iliac bone biopsy were performed within the first 2 months after renal transplantation and repeated after 2-5 years of follow-up. Follow-up biopsy revealed a significant decrease in osteoblast surface/bone surface (0.91 ± 0.81 to 0.47 ± 0.12%, P = 0.036), osteoblasts number/bone surface (0.45 (0.23, 0.94) to 0.00/mm(2) , P = 0.018) and erosion surface/bone surface (3.75 ± 2.02 to 2.22 ± 1.38%, P = 0.044). A decrease in trabecular number (3.55 (1.81, 2.89) to 1.55/mm (1.24, 2.06), P = 0.018) and increase in trabecular separation (351.65 ± 135.04 to 541.79 ± 151.91 μm, P = 0.024) in follow-up biopsy suggest loss in bone quantity. We found no significant differences in cortical analysis, except a reduction in external cortical osteonal eroded surface (5.76 (2.94, 13.97) to 3.29% (0.00, 6.67), P = 0.043). Correlations between bone histomorphometric and dual-X-ray absorptiometry parameters gave inconsistent results. The results show a reduction in bone activity, suggesting increased risk of adynamic bone and loss of bone volume. Cortical bone seems less affected by post-transplant biological changes in the first years after kidney transplantation. © 2015 Asian Pacific Society of Nephrology.

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients.

PubMed

Luckman, Matthew; Hans, Didier; Cortez, Natalia; Nishiyama, Kyle K; Agarawal, Sanchita; Zhang, Chengchen; Nikkel, Lucas; Iyer, Sapna; Fusaro, Maria; Guo, Edward X; McMahon, Donald J; Shane, Elizabeth; Nickolas, Thomas L

2017-04-03

Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid-withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (-0.45%±0.15%), separation (-0.40%±0.15%), and network heterogeneity (-0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P <0.05). Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients. Copyright © 2017 by the American Society of Nephrology.

Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients

PubMed Central

Luckman, Matthew; Hans, Didier; Cortez, Natalia; Nishiyama, Kyle K.; Agarawal, Sanchita; Zhang, Chengchen; Nikkel, Lucas; Iyer, Sapna; Fusaro, Maria; Guo, Edward X.; McMahon, Donald J.; Shane, Elizabeth

2017-01-01

Background and objectives Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients. Design, settings, participants, & measurements Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid–withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography. Results At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (−0.45%±0.15%), separation (−0.40%±0.15%), and network heterogeneity (−0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P<0.05). Conclusions Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients. PMID:28348031

Incorporation of Bone Marrow Cells in Pancreatic Pseudoislets Improves Posttransplant Vascularization and Endocrine Function

PubMed Central

Wittig, Christine; Laschke, Matthias W.; Scheuer, Claudia; Menger, Michael D.

2013-01-01

Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×103 cells. To create bone marrow cell-enriched pseudoislets 2×103 islet cells were co-cultured with 2×103 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation. PMID:23875013

Effect of Denosumab on Peripheral Compartmental Bone Density, Microarchitecture and Estimated Bone Strength in De Novo Kidney Transplant Recipients.

PubMed

Bonani, Marco; Meyer, Ursina; Frey, Diana; Graf, Nicole; Bischoff-Ferrari, Heike A; Wüthrich, Rudolf P

2016-01-01

In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known. The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14). Consistent with the full trial findings, denosumab reduced biomarkers of bone turnover, and significantly increased aBMD at the lumbar spine (median difference of 4.7%; 95% confidence interval [CI] 2.6 - 7.8; p<0.001). Bone quality as assessed by total and cortical volumetric bone mineral density (Tot. vBMD, Ct.vBMD) and cortical thickness (Ct.Th) increased significantly at the tibia, while changes at the radius were less pronounced. The trabecular volumetric BMD (Tb.vBMD), thickness (Tb. Th), separation (Tb.Sp) and number (Tb.N) and the cortical porosity (Ct.Po) at the tibia and the radius did not significantly change in both treatment groups. Micro-finite element analysis (µFEA) showed that bone stiffness increased significantly at the tibia (median difference 5.6%; 95% CI 1.8% - 9.2%; p=0.002) but not at the radius (median difference 2.9%, 95% CI -3.7% - 9.1%; p=0.369). Likewise, failure load increased significantly at the tibia (median difference 5.1%; 95% CI 2.1% - 8.1%; p=0.002) but not at the radius (median difference 2.4%, 95% CI -3.2% - 8.5%; p=0.336). These findings demonstrate that denosumab improves bone density and bone quality in first-year kidney transplant recipients at risk to develop osteoporosis. © 2016 The Author(s) Published by S. Karger AG, Basel.

Maladjustment of kidneys to microgravity: Design of measures to reduce the loss of calcium

NASA Technical Reports Server (NTRS)

Nechay, Bohdan R.

1989-01-01

Losses of skeletal calcium and body fluids occur during prolonged exposure to microgravity. The kidney plays a major role in regulating the physiological functions involved. Relative to this regulatory function, the kidney performs three operations: filtration of blood plasma through the glomeruli, reabsorption, and secretion of fluid and electrolytes so that needed components are retained and only waste is eliminated in the urine. Using data published in Biomedical Results from Skylab, researchers performed new calculations that reflect more directly the operations of the kidney in the handling of calcium, sodium, chloride, potassium and phosphate during space flight. These calculations revealed that the fraction of filtered calcium that was rejected by renal tubules and excreted in the urine increased by 71 percent, from 1.77 percent (preflight) to 3.02 percent (inflight) of the filtered load. This represents a large absolute increase because the total filtered amount is huge. Because the tubular rejection fraction of other ions increased relatively less than that of calcium, researchers postulate the inflight development of a specific renal defect that causes an excessive loss of calcium in urine and thereby contributes to the weakening of bones.

Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers.

PubMed

Bacchetta, Justine; Fargue, Sonia; Boutroy, Stéphanie; Basmaison, Odile; Vilayphiou, Nicolas; Plotton, Ingrid; Guebre-Egziabher, Fitsum; Dohin, Bruno; Kohler, Rémi; Cochat, Pierre

2010-06-01

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

Human exposure to metals: levels in autopsy tissues of individuals living near a hazardous waste incinerator.

PubMed

Mari, Montse; Nadal, Martí; Schuhmacher, Marta; Barbería, Eneko; García, Francisco; Domingo, José L

2014-06-01

The concentrations of a number of metals were determined in the brain, bone, kidney, liver, and lung of 20 autopsied subjects who had lived, at least 10 years, in the neighborhood of a hazardous waste incinerator (HWI) in Tarragona (Catalonia, Spain). Results were compared with those obtained in 1998 (baseline survey) and previous surveys (2003 and 2007). Arsenic, Be, Ni, Tl, and V showed concentrations below the corresponding detection limits in all tissues. Cadmium showed the highest levels in the kidney, with a mean value of 21.15 μg/g. However, Cd was found below the detection limit in the brain and bone. Chromium showed similar concentrations in the kidney, brain, and lung (range of mean values, 0.57-0.66 μg/g) and higher in the bone (1.38 μg/g). In turn, Hg was below the detection limit in all tissues with the exception of the kidney, where the mean concentration was 0.15 μg/g (range, <0.05-0.58 μg/g). On the other hand, Mn could be detected in all tissues showing the highest levels in the liver and kidney (1.45 and 1.09 μg/g, respectively). Moreover, Pb showed the highest concentrations in bone (mean, 1.39 μg/g; range, <0.025-4.88 μg/g). Finally, Sn could be detected only in some tissue samples, reaching the highest values in the bone (0.17 μg/g). The current metal levels in human tissues from individuals living near the HWI of Tarragona are comparable and of a similar magnitude to previously reported results corresponding to general populations, as well as those of our previous surveys.

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

PubMed

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

2018-05-21

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

Cholecystokinin Plays a Novel Protective Role in Diabetic Kidney Through Anti-inflammatory Actions on Macrophage

PubMed Central

Miyamoto, Satoshi; Shikata, Kenichi; Miyasaka, Kyoko; Okada, Shinichi; Sasaki, Motofumi; Kodera, Ryo; Hirota, Daisho; Kajitani, Nobuo; Takatsuka, Tetsuharu; Kataoka, Hitomi Usui; Nishishita, Shingo; Sato, Chikage; Funakoshi, Akihiro; Nishimori, Hisakazu; Uchida, Haruhito Adam; Ogawa, Daisuke; Makino, Hirofumi

2012-01-01

Inflammatory process is involved in the pathogenesis of diabetic nephropathy. In this article, we show that cholecystokinin (CCK) is expressed in the kidney and exerts renoprotective effects through its anti-inflammatory actions. DNA microarray showed that CCK was upregulated in the kidney of diabetic wild-type (WT) mice but not in diabetic intracellular adhesion molecule-1 knockout mice. We induced diabetes in CCK-1 receptor (CCK-1R) and CCK-2R double-knockout (CCK-1R−/−,-2R−/−) mice, and furthermore, we performed a bone marrow transplantation study using CCK-1R−/− mice to determine the role of CCK-1R on macrophages in the diabetic kidney. Diabetic CCK-1R−/−,-2R−/− mice revealed enhanced albuminuria and inflammation in the kidney compared with diabetic WT mice. In addition, diabetic WT mice with CCK-1R−/− bone marrow–derived cells developed more albuminuria than diabetic CCK-1R−/− mice with WT bone marrow–derived cells. Administration of sulfated cholecystokinin octapeptide (CCK-8S) ameliorated albuminuria, podocyte loss, expression of proinflammatory genes, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore, CCK-8S inhibited both expression of tumor necrosis factor-α and chemotaxis in cultured THP-1 cells. These results suggest that CCK suppresses the activation of macrophage and expression of proinflammatory genes in diabetic kidney. Our findings may provide a novel strategy of therapy for the early stage of diabetic nephropathy. PMID:22357963

Feeding soy protein isolate and oils rich in omega-3 polyunsaturated fatty acids affected mineral balance, but not bone in a rat model of autosomal recessive polycystic kidney disease.

PubMed

Maditz, Kaitlin H; Smith, Brenda J; Miller, Matthew; Oldaker, Chris; Tou, Janet C

2015-02-10

Polycystic kidney disease (PKD), a genetic disorder characterized by multiple cysts and renal failure at an early age. In children, kidney disease is often accompanied by disordered mineral metabolism, failure to achieve peak bone mass, and reduced adult height. Optimizing bone health during the growth stage may preserve against bone loss associated with early renal dysfunction in PKD. Dietary soy protein and omega-3 polyunsaturated fatty acid (n-3 PUFA) have been reported to ameliorate PKD and to promote bone health. The study objective was to determine the bone effects of feeding soy protein and/or n-3 PUFAs in a rat model of PKD. Weanling female PCK rats (n = 12/group) were randomly assigned to casein + corn oil (Casein + CO), casein + soybean oil (Casein + SO), soy protein isolate + soybean oil (SPI + SO) or soy protein isolate + 1:1 soybean oil:salmon oil blend (SPI + SB) for 12 weeks. Rats fed SPI + SO diet had shorter (P = 0.001) femur length than casein-fed rats. Rats fed SPI + SO and SPI + SB diet had higher (P = 0.04) calcium (Ca) and phosphorus (P) retention. However, there were no significant differences in femur and tibial Ca, P or bone mass between diet groups. There were also no significant difference in bone microarchitecture measured by micro-computed tomography or bone strength determined by three-point bending test between diet groups. Early diet management of PKD using SPI and/or n-3 PUFAs influenced bone longitudinal growth and mineral balance, but neither worsened nor enhanced bone mineralization, microarchitecture or strength.

Tissue distribution of metals in white-fronted geese and spot-billed ducks from Korea.

PubMed

Kim, Jungsoo; Oh, Jong-Min

2013-07-01

This study presents concentrations of Fe, Zn, Mn, Cu, Pb and Cd in livers, kidneys, muscles and bones of white-fronted geese Anser albifrons (geese) and spot-billed ducks Anas poecilorhyncha (ducks). Iron in livers, kidneys and muscles, Zn in muscles, Mn and Cd in every tissue, Cu in livers, muscles and bones and Pb in bones differed between species, and there were significant differences among tissues in both species. Essential elements such as Fe, Zn, Mn and Cu concentrations were within the background levels. Lead concentrations in livers of 7 of 14 geese and 7 of 19 ducks and in bones of 4 of 19 ducks exceeded background concentrations for waterfowl (5 μg/g dw for the liver, 10 μg/g dw for the bone). Almost all samples of both species had the background Cd concentrations in the liver (33 of 33 geese and ducks) and kidney (14 geese and 18 ducks). Tissue concentrations of Cd were greater in geese than ducks. In contrast, tissue concentrations of Pb in bones were greater in ducks than in geese. These different trends for Cd and Pb reflect a short and/or long term difference in exposure and degree of accumulation of these metals.

Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study.

PubMed

Lee, Hyunah; Park, Jae Berm; Lee, Sanghoon; Baek, Soyoung; Kim, HyunSoo; Kim, Sung Joo

2013-04-11

Mesenchymal stem cells (MSCs) are multi-potent non-hematopoietic progenitor cells possessing an immune-regulatory function, with suppression of proliferation of activated lymphocytes. In this study, adult living donor kidney transplantation (LDKT) recipients were given MSCs derived from the donor bone marrow to evaluate the safety and the feasibility of immunological changes related to the intra-osseous injection of MSC into the bone marrow. MSCs were derived from negative HLA cross-match donors. Donor bone marrow was harvested 5 weeks prior to KT. At the time of transplantation, 1 x 106 cell/kg of donor MSC was directly injected into the bone marrow of the recipient's right iliac bone. Patients' clinical outcomes, presence of mixed chimerism by short tandem repeat polymerase chain reaction, analysis of plasma FoxP3 mRNA and cytokine level, and mixed lymphocyte reaction (MLR) were performed. Seven patients enrolled in this study and received donor MSC injections simultaneously with LDKT. The median age of recipients was 36 years (32 ~ 48). The number of HLA mismatches was 3 or less in 5 and more than 3 in 2. No local complications or adverse events such as hypersensitivity occurred during or after the injection of donor MSC. There was no graft failure, but the biopsy-proven acute rejections were observed in 3 recipients during the follow-up period controlled well with steroid pulse therapy (SPT). The last serum creatinine was a median of 1.23 mg/dL (0.83 ~ 2.07). Mixed chimerism was not detected in the peripheral blood of the recipients at 1 and 8 week of post-transplantation. Donor-specific lymphocyte or T cell proliferation and Treg priming responses were observed in some patients. Plasma level of IL-10, a known mediator of MSC-induced immune suppression, increased in the patients with Treg induction. Donor MSC injection into the iliac bone at the time of KT was feasible and safe. A possible correlation was observed between the induction of inhibitory immune responses and the clinical outcome in the MSC-kidney transplanted patients. Further research will be performed to evaluate the efficacy of MSC injection for the induction of mixed chimerism and subsequent immune tolerance in KT.

Kidney versus Islet Allograft Survival after Induction of Mixed Chimerism with Combined Donor Bone Marrow Transplantation

PubMed Central

Oura, Tetsu; Ko, Dicken S.C.; Boskovic, Svjetlan; O'Neil, John J.; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R. Neal; Cosimi, A. B.; Kawai, Tatsuo

2016-01-01

Background We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC-mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. Methods A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that includes low dose total body and thymic irradiation, horse ATG (Atgam), six doses of anti-CD154 monoclonal antibody (mAb) and a one month course of cyclosporine (CyA) (Islet-A). In Islet-B, anti-CD8 mAb was administered in place of CyA. In Islet-C, two recipients were treated with Islet-B but without Atgam. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and bone marrow transplantation (Kidney-A) following the same conditioning regimen used in Islet-A. Results The majority of Kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned Islet/BM recipients (Islet-A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to calcineurin inhibitor (CNI) toxicity, three recipients were treated with anti-CD8 mAb in place of CNI. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet-C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Conclusion Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CNI-free regimen that includes anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more durable mixed chimerism may be necessary for induction of islet allograft tolerance. PMID:26337731

[Bone metabolism and cardiovascular function Update. Vascular calcification as a manifestation of bone-vascular axis].

PubMed

Kurabayashi, Masahiko

2014-07-01

Vascular calcification is the major cause of cardiovascular morbidity and mortality in the patients with type 2 diabetes, chronic kidney disease and in aging patients. Regardless of the morphology and location, most evidence indicates that vascular calcification involves an organized process recapitulating many cellular and molecular events that govern skeletal bone formation. While the large body of evidence that osteoblastic and osteochondrocytic cells contribute to vascular calcification, it remains unclear how osteoclasts are differentiated from their precursors and how osteoclasts play a role in calcium reabsorption in calcifying arteries. It is reassuring that calcium paradox is not merely due to the calcium shift from bone to artery wall, but is likely due to the differential response of both osteoblasts and osteoclasts to oxidative stress between bone and artery. To date, many studies have highlighted the important role for RANK/RANKL/OPG axis as unifying theme for the apparently opposite regulation of calcification between two tissues.

Fracture Risk Assessment in Chronic Kidney Disease, Prospective Testing Under Real World Environments (FRACTURE): a prospective study.

PubMed

West, Sarah L; Lok, Charmaine E; Jamal, Sophie A

2010-08-20

Chronic kidney disease (CKD) is associated with an increased risk of fracture. Decreased bone mass and disruption of microarchitecture occur early in the course of CKD and worsens with the progressive decline in renal function so that at the time of initiation of dialysis at least 50% of patients have had a fracture. Despite the excess fracture risk, and the associated increases in morbidity and mortality, little is known about the factors that are associated with an increase in fracture risk. Our study aims to identify prognostic factors for bone loss and fractures in patients with stages 3 to 5 CKD. This prospective study aims to enroll two hundred and sixty men and women with stages 3 to 5 CKD. Subjects will be followed for 24 months and we will examine the ability of: 1) bone mineral density by dual x-ray absorptiometry at the spine, hip, and radius; 2) volumetric bone density by high resolution peripheral quantitated computed tomography at the radius and tibia; 3) serum markers of bone turnover; 4) bone formation rate by bone biopsy; and 5) muscle strength and balance to predict spine and non-spine fractures, identified by self-report and/or vertebral morphometry. All measurements will be obtained at baseline, at 12 and at 24 months with the exception of bone biopsy, which will be measured once at 12 months. Subjects will be contacted every 4 months to determine if there have been incident fractures or falls. This study is one of the first that aims to identify risk factors for fracture in early stage CKD patients. Ultimately, by identifying risk factors for fracture and targeting treatments in this group-before the initiation of renal replacement therapy--we will reduce the burden of disease due to fractures among patients with CKD.

Extracellular calcium (Ca2+o)-sensing receptor in a mouse monocyte-macrophage cell line (J774): potential mediator of the actions of Ca2+o on the function of J774 cells

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Kifor, O.; Chattopadhyay, N.; Bai, M.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

1998-01-01

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone resorption during bone remodeling and may play a role in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for bone marrow mononuclear cells in the vicinity, leading us to investigate whether such mononuclear cells express the CaR. In this study, we used the mouse J774 cell line, which exhibits a pure monocyte-macrophage phenotype. Both immunocytochemistry and Western blot analysis, using polyclonal antisera specific for the CaR, detected CaR protein in J774 cells. The use of reverse transcriptase-polymerase chain reaction with CaR-specific primers, including a set of intron-spanning primers, followed by nucleotide sequencing of the amplified products, also identified CaR transcripts in J774 cells. Exposure of J774 cells to high Ca2+o (2.8 mM or more) or the polycationic CaR agonist, neomycin (100 microM), stimulated both chemotaxis and DNA synthesis in J774 cells. Therefore, taken together, our data strongly suggest that the monocyte-macrophage cell line, J774, possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney.

Morphometric and functional abnormalities of kidneys in the progeny of mice fed chocolate during pregnancy and lactation.

PubMed

Patera, Janusz; Chorostowska-Wynimko, Joanna; Słodkowska, Janina; Borowska, Adamina; Skopiński, Piotr; Sommer, Ewa; Wasiutyński, Aleksander; Skopińska-Rózewska, Ewa

2006-01-01

Even most commonly consumed beverages like tea, coffee, chocolate and cocoa contain methylxanthines, biogenic amines and polyphenols, among them catechins, that exhibit significant biological activity and might profoundly affect the organism homeostasis. We have previously shown that 400 mg of bitter chocolate or 6 mg of theobromine added to the daily diet of pregnant and afterwards lactating mice affected embryonic angiogenesis and caused bone mineralization disturbances as well as limb shortening in 4-weeks old offspring. The aim of the present study was the morphometric and functional evaluation of kidneys in the 4-weeks old progeny mice fed according to the protocol mentioned above. Progeny from the mice fed chocolate presented considerable morphometric abnormalities in the kidney structure, with the lower number of glomeruli per mm2 and their increased diameter. Moreover, higher serum creatinine concentration was observed in that group of offspring. No morphometric or functional irregularities were found in the progeny of mice fed theobromine. Abnormalities demonstrated in the offspring of mice fed chocolate are not related to its theobromine content. Consequently, identification of active compound(s) responsible for the observed effects is of vital importance.

Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference.

PubMed

Ketteler, Markus; Elder, Grahame J; Evenepoel, Pieter; Ix, Joachim H; Jamal, Sophie A; Lafage-Proust, Marie-Hélène; Shroff, Rukshana; Thadhani, Ravi I; Tonelli, Marcello A; Kasiske, Bertram L; Wheeler, David C; Leonard, Mary B

2015-03-01

A new definition and classification of chronic kidney disease-mineral and bone disorder (CKD-MBD) was proposed in 2005 and it was later followed by a guideline publication on this topic from Kidney Disease: Improving Global Outcomes (KDIGO) in 2009. This work recognized that CKD-MBD is a syndrome of bone abnormalities, laboratory abnormalities, and vascular calcification linked to fractures, cardiovascular disease, and mortality. Because of limited data at the time of the original guideline systematic review, many of the recommendations were cautiously vague. KDIGO convened a Controversies Conference in October 2013 to review the CKD-MBD literature published since the 2009 guideline. Specifically, the objective of this conference was to determine whether sufficient new data had emerged to support a reassessment of the CKD-MBD guideline and if so to determine the scope of these potential revisions. This report summarizes the results of these proceedings, highlighting important new studies conducted in the interval since the original KDIGO CKD-MBD guideline.

[Ornithine decarboxylase in mammalian organs and tissues at hibernation and artificial hypobiosis].

PubMed

Logvinovich, O S; Aksenova, G E

2013-01-01

Ornithine decarboxylase (ODC, EC 4.1.1.17.) is a short-lived and dynamically regulated enzyme of polyamines biosynthesis. Regulation of functional, metabolic and proliferative state of organs and tissues involves the modifications of the ODC enzymatic activity. The organ-specific changes in ODC activity were revealed in organs and tissues (liver, spleen, bone marrow, kidney, and intestinal mucosa) of hibernating mammals - squirrels Spermophilus undulates - during the hibernating season. At that, a positive correlation was detected between the decline and recovery of the specialized functions of organs and tissues and the respective modifications of ODC activity during hibernation bouts. Investigation of changes in ODC activity in organs and tissues of non-hibernating mammals under artificial hypobiosis showed that in Wistar rats immediately after exposure to hypothermia-hypoxia-hypercapnia (hypobiosis) the level of ODC activity was low in thymus, spleen, small intestine mucosa, neocortex, and liver. The most marked reduction in enzyme activity was observed in actively proliferating tissues: thymus, spleen, small intestine mucosa. In bone marrow of squirrels, while in a state of torpor, as well as in thymus of rats after exposure to hypothermia-hypoxia-hypercapnia, changes in the ODC activity correlated with changes in the rate of cell proliferation (by the criterion of cells distribution over cell cycle). The results obtained, along with the critical analysis of published data, indicate that the ODC enzyme is involved in biochemical adaptation of mammals to natural and artificial hypobiosis. A decline in the ODC enzymatic activity indicates a decline in proliferative, functional, and metabolic activity of organs and tissues of mammals (bone marrow, mucosa of small intestine, thymus, spleen, neocortex, liver, kidneys) when entering the state of hypobiosis.

The frequency of bone fractures among patients with chronic kidney disease not on dialysis: two-year follow-up.

PubMed

Figurek, Andreja; Vlatkovic, Vlastimir; Vojvodic, Dragan; Gasic, Branislav; Grujicic, Milorad

2017-12-01

Renal osteodystrophy is a severe complication of chronic kidney disease (CKD) that increases morbidity and mortality in these patients. Mineral and bone disorder starts early in CKD and affects the incidence of bone fractures. The aim of this study was to observe the frequency of diverse bone fractures in patients with CKD not on dialysis. This cohort study included 68 patients that were followed during the two-year period. The patients were divided into two cohorts: one that developed bone fractures and the other that did not. There were 35 (51.5%) men and 33 (48.5%) women. The mean age of patients ranged 62.88±11.60 years. During follow-up serum values of chronic kidney disease - mineral and bone indicators were measured. The methods of descriptive and analytical statistics were used in order to analyze obtained data. During this two-year follow-up seven patients developed bone fractures. Among them, females dominated (6 patients) compared to males (only 1 patient). The most common were fractures of forearm. The mean level of parathyroid hormone (PTH) at the beginning of the monitoring was higher in the group of patients with bone fractures (165.25 ± 47.69 pg/mL) in regard to another group (103.96 ± 81.55 pg/mL). After two-year follow-up, this difference became statistically significant at the level p < 0.05. Patients that developed bone fractures had higher FRAX (Fracture Risk Assessment) score compared to another group. In our study, about 10% of patients had bone fractures in the two-year follow-up period. Patients who developed fractures had a higher PTH level and FRAX score.

Calcitonin and calcitonin receptors: bone and beyond

PubMed Central

Pondel, Marc

2000-01-01

Calcitonin (CT), a 32 amino acid peptide hormone produced primarily by the thyroid, and its receptor (CTR) are well known for their ability to regulate osteoclast mediated bone resorption and enhance Ca2+ excretion by the kidney. However, recent studies now suggest that CT and CTRs may play an important role in a variety of processes as wide ranging as embryonic/foetal development and sperm function/physiology. In this review article, CT and CTR gene transcription, signal transduction and function are addressed. The effects of CT on the physiology of a variety of organ systems are discussed and the relationship between polymorphisms in the CTR gene and bone mineral density (BMD)/osteoporosis is examined. Recent studies demonstrating the ability of receptor activity modifying proteins (RAMPs) to post-translationally modify the calcitonin receptor-like receptor (CRLR) are detailed and studies employing transgenic mouse technology to determine the temporal and tissue specific transcriptional activity of the CTR gene in vivo are discussed. PMID:11298188

[Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].

PubMed

Xiao, Ya-Ping; Zeng, Jie; Jiao, Lin-Na; Xu, Xiao-Yu

2018-01-01

The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/ β -catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/ β -catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification. Copyright© by the Chinese Pharmaceutical Association.

Texas Emergency Resource Management. Volume II.

DTIC Science & Technology

1979-09-30

direct all users and distributors of sugar and other natural sweeteners in the State to abide by such regulations as may be issued by the U. S. Department...systemic disorders such a, arthritis, heart disease, diabetes or kidney trouble. May treat bone, muscle and joint disorders limits to feet and be kno...dis- orders such as arthritis, heart disease, diabetes or kidney trouble. May treat bone, muscle and joint disorders limited to feet and be known as

Late conversion from tacrolimus to a belatacept-based immuno-suppression regime in kidney transplant recipients improves renal function, acid-base derangement and mineral-bone metabolism.

PubMed

Schulte, Kevin; Vollmer, Clara; Klasen, Vera; Bräsen, Jan Hinrich; Püchel, Jodok; Borzikowsky, Christoph; Kunzendorf, Ulrich; Feldkamp, Thorsten

2017-08-01

Calcineurin inhibitor (CNI)-induced nephrotoxicity and chronic graft dysfunction with deteriorating glomerular filtration rate (GFR) are common problems of kidney transplant recipients. The aim of this study was to analyze the role of belatacept as a rescue therapy in these patients. In this retrospective, observational study we investigated 20 patients (10 females, 10 males) who were switched from a CNI (tacrolimus) to a belatacept-based immunosuppression because of CNI intolerance or marginal transplant function. Patient follow-up was 12 months. Patients were converted to belatacept in mean 28.8 months after transplantation. Reasons for conversion were CNI intolerance (14 patients) or marginal transplant function (6 patients). Mean estimated GFR (eGFR) before conversion was 22.2 ± 9.4 ml/min at baseline and improved significantly to 28.3 ± 10.1 ml/min at 4 weeks and to 32.1 ± 12.6 ml/min at 12 months after conversion. Serum bicarbonate significantly increased from 24.4 ± 3.2 mmol/l at baseline to 28.7 ± 2.6 mmol/l after 12 months. Conversion to belatacept decreased parathyroid hormone and phosphate concentrations significantly, whereas albumin levels significantly increased. In 6 cases an acute rejection preceded clinically relevant CNI toxicity; only two patients suffered from an acute rejection after conversion. Belatacept was well tolerated and there was no increase in infectious or malignant side effects. A late conversion from a tacrolimus-based immunosuppression to belatacept is safe, effective and significantly improves renal function in kidney transplant recipients. Additionally, the conversion to belatacept has a beneficial impact on acid-base balance, mineral-bone and protein metabolism, independently of eGFR.

Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury.

PubMed

Toro, Luis; Barrientos, Víctor; León, Pablo; Rojas, Macarena; Gonzalez, Magdalena; González-Ibáñez, Alvaro; Illanes, Sebastián; Sugikawa, Keigo; Abarzúa, Néstor; Bascuñán, César; Arcos, Katherine; Fuentealba, Carlos; Tong, Ana María; Elorza, Alvaro A; Pinto, María Eugenia; Alzamora, Rodrigo; Romero, Carlos; Michea, Luis

2018-05-01

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Paracrine Activation of the Wnt/β-Catenin Pathway by Bone Marrow Stem Cell Attenuates Cisplatin-Induced Kidney Injury.

PubMed

Jiao, Xiaoyan; Cai, Jieru; Yu, Xiaofang; Ding, Xiaoqiang

2017-01-01

Cisplatin-induced acute kidney injury (AKI) involves damage to tubular cells via excess reactive oxygen species (ROS) generation. Stem cell-based therapies have shown great promise in AKI treatment. In this study, we aimed to assess the protective effect and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived conditioned medium (CM) against cisplatin-induced AKI. In vitro, NRK-52E cells were incubated with cisplatin in the presence or absence of CM, followed by the assessment of cell viability, apoptosis and cell cycle distribution. Then, ICG-001 and IWR-1 were used to inhibit the wnt/β-catenin pathway. Furthermore, intracellular and mitochondrial ROS levels were evaluated using DCFH-DA and MitoSOX, respectively. In vivo, after cisplatin injection, rats were intravenously injected with CM or BMSCs. Sera and kidney tissues were collected on day 3 after cisplatin injection to evaluate changes in renal function and histology. Western blotting and qRT-PCR were employed to determine the expression of wnt/β-catenin pathway-related genes and proteins. Immunohistochemical staining was used to evaluate tubular β-catenin expression in kidney biopsy from AKI patients. CM protected NRK-52E cells from cisplatin-induced injury by restoring the wnt4/β-catenin pathway. In response to ICG-001 and IWR-1, the protective effect of CM was attenuated, characterized by a decrease in cell proliferation and an increase in cell apoptosis and intracellular and mitochondrial ROS levels. Knockdown of β-catenin using siRNAs also suppressed the mitochondrial biogenesis regulators PGC-1α, TFAM and NRF-1. In the rat model, CM significantly alleviated renal function and histology associated with tubular injury and upregulated wnt4 and β-catenin. However, the renoprotective effect of CM was blocked by ICG-001, characterized by exacerbated renal function, suppressed PGC-1α expression and increased mitochondrial ROS. Clinical data showed that the tubular β-catenin level was lower in AKI patients experiencing partial recovery than in patients experiencing complete recovery. The activation of the wnt/β-catenin pathway by CM protects against cisplatin-induced kidney injury, resulting in reduced apoptosis and intracellular ROS levels. © 2017 The Author(s). Published by S. Karger AG, Basel.

A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D3 activation

PubMed Central

Meyer, Mark B.; Benkusky, Nancy A.; Kaufmann, Martin; Lee, Seong Min; Onal, Melda; Jones, Glenville; Pike, J. Wesley

2017-01-01

The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1, are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH)2D3-mediated regulation of Cyp27b1 expression. Selective genomic deletion of key components within this module in mice resulted in loss of either PTH induction or FGF23 and 1,25(OH)2D3 suppression of Cyp27b1 gene expression; the former loss caused a debilitating skeletal phenotype, whereas the latter conferred a quasi-normal bone mineral phenotype through compensatory homeostatic mechanisms involving Cyp24a1. We found that Cyp27b1 is also expressed at low levels in non-renal cells, in which transcription was modulated exclusively by inflammatory factors via a process that was unaffected by deletion of the kidney-specific module. These results reveal that differential regulation of Cyp27b1 expression represents a mechanism whereby 1,25(OH)2D3 can fulfill separate functional roles, first in the kidney to control mineral homeostasis and second in extra-renal cells to regulate target genes linked to specific biological responses. Furthermore, we conclude that these mouse models open new avenues for the study of vitamin D metabolism and its involvement in therapeutic strategies for human health and disease. PMID:28808057

Concise Review: Kidney Stem/Progenitor Cells: Differentiate, Sort Out, or Reprogram?

PubMed Central

Pleniceanu, Oren; Harari-Steinberg, Orit; Dekel, Benjamin

2010-01-01

End-stage renal disease (ESRD) is defined as the inability of the kidneys to remove waste products and excess fluid from the blood. ESRD progresses from earlier stages of chronic kidney disease (CKD) and occurs when the glomerular filtration rate (GFR) is below 15 ml/minute/1.73 m2. CKD and ESRD are dramatically rising due to increasing aging population, population demographics, and the growing rate of diabetes and hypertension. Identification of multipotential stem/progenitor populations in mammalian tissues is important for therapeutic applications and for understanding developmental processes and tissue homeostasis. Progenitor populations are ideal targets for gene therapy, cell transplantation, and tissue engineering. The demand for kidney progenitors is increasing due to severe shortage of donor organs. Because dialysis and transplantation are currently the only successful therapies for ESRD, cell therapy offers an alternative approach for kidney diseases. However, this approach may be relevant only in earlier stages of CKD, when kidney function and histology are still preserved, allowing for the integration of cells and/or for their paracrine effects, but not when small and fibrotic end-stage kidneys develop. Although blood- and bone marrow-derived stem cells hold a therapeutic promise, they are devoid of nephrogenic potential, emphasizing the need to seek kidney stem cells beyond known extrarenal sources. Moreover, controversies regarding the existence of a true adult kidney stem cell highlight the importance of studying cell-based therapies using pluripotent cells, progenitor cells from fetal kidney, or dedifferentiated/reprogrammed adult kidney cells. Stem Cells 2010; 28:1649–1660. PMID:20652959

Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

ClinicalTrials.gov

2017-03-21

Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

Chronic Kidney Disease.

PubMed

Webster, Angela C; Nagler, Evi V; Morton, Rachael L; Masson, Philip

2017-03-25

The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m 2 , or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cell Biology of Thiazide Bone Effects

NASA Astrophysics Data System (ADS)

Gamba, Gerardo; Riccardi, Daniela

2008-09-01

The thiazide-sensitive Na+:Cl- cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian kidney. The activity of NCC is not only related to salt metabolism, but also to calcium and magnesium homeostasis due to the inverse relationship between NCC activity and calcium reabsorption. Hence, the thiazide-type diuretics that specifically block NCC have been used for years, not only for treatment of hypertension and edematous disease, but also for the management of renal stone disease. Epidemiological studies have shown that chronic thiazide treatment is associated with higher bone mineral density and reduced risk of bone fractures, which can only partly be explained in terms of their effects on the kidney. In this regard, we have recently shown that NCC is expressed in bone cells and that inhibition of NCC in bone, either by thiazides or by reduction of NCC protein with specific siRNA, is associated with increased mineralization in vitro. These observations open a field of study to begin to understand the cell biology of the beneficial effects of thiazides in bone.

Raloxifene improves skeletal properties in an animal model of cystic chronic kidney disease

PubMed Central

Newman, Christopher L.; Creecy, Amy; Granke, Mathilde; Nyman, Jeffry S.; Tian, Nannan; Hammond, Max A.; Wallace, Joseph M.; Brown, Drew M.; Chen, Neal; Moe, Sharon M.; Allen, Matthew R.

2015-01-01

Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild anti-resorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared to normal controls as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. While it had little effect on cortical bone geometry it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole bone mechanical properties in CKD through its impact on skeletal material properties. PMID:26489025

Phosphate homeostasis in CKD: report of a scientific symposium sponsored by the National Kidney Foundation.

PubMed

Block, Geoffrey A; Ix, Joachim H; Ketteler, Markus; Martin, Kevin J; Thadhani, Ravi I; Tonelli, Marcello; Wolf, Myles; Jüppner, Harald; Hruska, Keith; Wheeler, David C

2013-09-01

Chronic kidney disease (CKD)-mineral and bone disorder is associated with diverse metabolic and endocrine disturbances that ultimately may contribute to further loss of kidney function, bone demineralization, and fatal or nonfatal cardiovascular events. Recent insights into the pathophysiology of the events that unfold during the development of this disorder suggest that disturbances in phosphate metabolism are pivotal. The consequences of abnormal phosphate homeostasis are evident at estimated glomerular filtration rates <70 mL/min/1.73 m(2), long before serum phosphate levels increase. Healthy individuals with blood phosphate levels in the top quartile of the normal range have an increased risk of developing CKD, reaching end-stage renal disease, and experiencing cardiovascular events. Substantial public health consequences may be related to increased dietary phosphorus exposure from additives that contain phosphate in the food supply and from modest increases in serum phosphate levels; however, it remains to be established whether interventions aimed at these targets can impact on the development of adverse clinical outcomes. Current approaches involving dietary intervention and intestinal phosphate binders are based on principles and assumptions that need to be examined more rigorously. Compelling animal, observational, and clinical data indicate that interventions directed at lowering phosphate exposure and serum phosphate levels should be subject to rigorous clinical trials that use appropriate placebo comparators and focus on key clinical outcomes, such as cardiovascular events, progression of CKD, fractures, quality of life, and mortality. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

DTIC Science & Technology

2017-09-01

the ideal solution. Combined mixed allogeneic chimerism induction and kidney transplantation has been shown to induce robust tolerance to the kidney ...induction to kidney allografts in non-human primates and humans despite the transience of donor chimerism. However, evidence indicates that durable mixed...chimerism may be required for tolerance induction to tissues or organs other than kidney . Amnion-derived multipotent progenitor (AMP) cells possess

Physical Therapy Considerations for Chronic Kidney Disease and Secondary Sarcopenia

PubMed Central

Hernandez, Haniel J.; Obamwonyi, Gideon; Harris-Love, Michael O.

2018-01-01

Chronic kidney disease (CKD) is a progressive condition that may negatively affect musculoskeletal health. These comorbidities may include malnutrition, osteoporosis, and decreased lean body mass. Secondary sarcopenia due to CKD may be associated with mobility limitations and elevated fall risk. Physical therapists are well-positioned among the health care team to screen for secondary sarcopenia in those with CKD and for the treatment of musculoskeletal comorbid conditions that may affect functional performance. Given the consequences of both low muscle mass and low bone mineral density, appropriate and timely physical therapy is important for fall risk assessment and intervention to minimize the susceptibility to bone fracture. While strength training has been studied less frequently than aerobic training for the management of secondary CKD conditions, evidence suggests that this patient population benefits from participation in strength training programs. However, the provision of a formal exercise prescription by a health care professional, along with formal implementation of an exercise program, may need to be more fully integrated into the standard plan of care for individuals with CKD. PMID:29376141

Mineral & Bone Disorder in Chronic Kidney Disease

MedlinePlus

... blood pressure. Once damaged, the kidneys can’t filter blood as they should. This damage can cause ... machine to circulate a person’s blood through a filter outside the body. The blood passes from a ...

Paricalcitol Versus Calcifediol for Treating Hyperparathyroidism in Kidney Transplant Recipients.

PubMed

Cruzado, Josep M; Lauzurica, Ricardo; Pascual, Julio; Marcen, Roberto; Moreso, Francesc; Gutierrez-Dalmau, Alex; Andrés, Amado; Hernández, Domingo; Torres, Armando; Beneyto, Maria Isabel; Melilli, Edoardo; Manonelles, Anna; Arias, Manuel; Praga, Manuel

2018-01-01

Secondary hyperparathyroidism (SHPT) and vitamin D deficiency are common at kidney transplantation and are associated with some early and late complications. This study was designed to evaluate whether paricalcitol was more effective than nutritional vitamin D for controlling SHPT in de novo kidney allograft recipients. This was a 6-month, investigator-initiated, multicenter, open-label, randomized clinical trial. Patients with pretransplantation iPTH between 250 and 600 pg/ml and calcium <10 mg/dl were randomized to paricalcitol (PAR) or calcifediol (CAL). The intention-to-treat population (PAR: n = 46; CAL: n = 47) was used for the analysis. The primary endpoint was the percentage of patients with serum iPTH >110 pg/ml at 6 months. Secondary endpoints were bone mineral metabolism, renal function, and allograft protocol biopsies. The primary outcome occurred in 19.6% of patients in the PAR group and 36.2% of patients in the CAL group ( P  = 0.07). However, there was a higher percentage of patients with iPTH <70 pg/ml in the PAR group than in the CAL group (63.4% vs. 37.2%; P  = 0.03). No differences were observed in bone turnover biomarkers and bone mineral density. The estimated glomerular filtration rate was significantly higher in the CAL group than in the PAR group without differences in albuminuria. In protocol biopsies, interstitial fibrosis and tubular atrophy tended to be higher in the PAR group than in the CAL group (48% vs. 23.8%; P  = 0.09). Both medications were well tolerated. Both PAR and CAL reduced iPTH, but PAR was associated with a higher proportion of patients with iPTH <70 pg/ml. These results do not support the use of PAR to treat posttransplantation hyperparathyroidism.

An interdisciplinary consensus on the management of bone metastases from renal cell carcinoma.

PubMed

Grünwald, Viktor; Eberhardt, Berit; Bex, Axel; Flörcken, Anne; Gauler, Thomas; Derlin, Thorsten; Panzica, Martin; Dürr, Hans Roland; Grötz, Knut Achim; Giles, Rachel H; von Falck, Christian; Graser, Anno; Muacevic, Alexander; Staehler, Michael

2018-06-14

Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future.

Extracellular calcium (Ca2+(o))-sensing receptor in a murine bone marrow-derived stromal cell line (ST2): potential mediator of the actions of Ca2+(o) on the function of ST2 cells

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Chattopadhyay, N.; Kifor, O.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

1998-01-01

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+(o)) homeostasis by mediating the actions of Ca2+(o) on parathyroid gland and kidney. Bone marrow stromal cells support the formation of osteoclasts from their progenitors as well as the growth of hematopoietic stem cells by secreting humoral factors and through cell to cell contact. Stromal cells also have the capacity to differentiate into bone-forming osteoblasts. Bone resorption by osteoclasts probably produces substantial local increases in Ca2+(o) that could provide a signal for stromal cells in the immediate vicinity, leading us to determine whether such stromal cells express the CaR. In this study, we used the murine bone marrow-derived, stromal cell line, ST2. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in ST2 cells. We also identified CaR transcripts in ST2 cells by Northern analysis using a CaR-specific probe and by RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of ST2 cells to high Ca2+(o) (4.8 mM) or to the polycationic CaR agonists, neomycin (300 microM) or gadolinium (100 microM), stimulated both chemotaxis and DNA synthesis in ST2 cells. Therefore, taken together, our data strongly suggest that the bone marrow-derived stromal cell line, ST2, possesses both CaR protein and messenger RNA that are very similar if not identical to those in parathyroid and kidney. Furthermore, as ST2 cells have the potential to differentiate into osteoblasts, the CaR in stromal cells could participate in bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local, osteoclast-mediated release of Ca2+(o) and, thereafter, initiating bone formation after their differentiation into osteoblasts.

Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

PubMed

Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

2017-12-01

The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

Prevalence and risk factors for kidney stones in fibrodysplasia ossificans progressiva.

PubMed

Gupta, Rishi R; Delai, Patricia L R; Glaser, David L; Rocke, David M; Al Mukaddam, Mona; Pignolo, Robert J; Kaplan, Frederick S

2018-04-01

The worldwide prevalence and risk factors for kidney stones in patients with fibrodysplasia ossificans progressiva (FOP) are unknown. We conducted a survey of 383 patient-members of the International Fibrodysplasia Ossificans Progressiva Association, comprising the entire global membership of the international FOP community. Two hundred seven patients from 31 nations and 6 continents (54%) responded. Nineteen of 207 respondents had kidney stones, revealing a worldwide prevalence of 9.2%. In a confirmatory follow-up study of subjects participating in a longitudinal FOP natural history study, 9 of 114 individuals reported a history of kidney stones (7.9%). In both study populations patients with kidney stones were found to be more functionally impaired compared to those without nephrolithiasis. The prevalence of kidney stones in the adult FOP population of the Unites States was 15.8% (9/57 individuals) compared to a sex- and age-weighted prevalence of 4.5% (p=4×10 -5 ) in the general population. Although geographical variation exists, patients with FOP have an approximately three-fold greater prevalence of kidney stones than the general population. This unusually high prevalence may be due to high bone turnover from chronic immobilization, or to unknown mechanistic effects of the activating FOP mutation in activin A receptor, type I/activin-like kinase-2 (ACVR1/ALK2), increasing the disease burden and morbidity in this already disabling condition. Copyright © 2017 Elsevier Inc. All rights reserved.

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis

PubMed Central

Micanovic, Radmila; Chitteti, Brahmananda R.; Dagher, Pierre C.; Srour, Edward F.; Khan, Shehnaz; Hato, Takashi; Lyle, Allison; Tong, Yan; Wu, Xue-Ru

2015-01-01

Tamm-Horsfall protein (THP) is a glycoprotein uniquely expressed in the kidney. We recently showed an important role for THP in mediating tubular cross-talk in the outer medulla and in suppressing neutrophil infiltration after kidney injury. However, it remains unclear whether THP has a broader role in neutrophil homeostasis. In this study, we show that THP deficiency in mice increases the number of neutrophils, not only in the kidney but also in the circulation and in the liver, through enhanced granulopoiesis in the bone marrow. Using multiplex ELISA, we identified IL-17 as a key granulopoietic cytokine specifically upregulated in the kidneys but not in the liver of THP−/− mice. Indeed, neutralization of IL-17 in THP−/− mice completely reversed the systemic neutrophilia. Furthermore, IL-23 was also elevated in THP−/− kidneys. We performed real-time PCR on laser microdissected tubular segments and FACS-sorted renal immune cells and identified the S3 proximal segments, but not renal macrophages, as a major source of increased IL-23 synthesis. In conclusion, we show that THP deficiency stimulates proximal epithelial activation of the IL-23/IL-17 axis and systemic neutrophilia. Our findings provide evidence that the kidney epithelium in the outer medulla can regulate granulopoiesis. When this novel function is added to its known role in erythropoiesis, the kidney emerges as an important regulator of the hematopoietic system. PMID:25556169

Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats

PubMed Central

Sakr, Saber; Rashed, Laila; Zarouk, Waheba; El-Shamy, Rania

2013-01-01

Objective To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis. Methods Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected. Results Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased. Conclusions The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s). PMID:23620833

Vegetarian Diet in Chronic Kidney Disease—A Friend or Foe

PubMed Central

Gluba-Brzózka, Anna; Franczyk, Beata; Rysz, Jacek

2017-01-01

Healthy diet is highly important, especially in patients with chronic kidney disease (CKD). Proper nutrition provides the energy to perform everyday activities, prevents infection, builds muscle, and helps to prevent kidney disease from getting worse. However, what does a proper diet mean for a CKD patient? Nutrition requirements differ depending on the level of kidney function and the presence of co-morbid conditions, including hypertension, diabetes, and cardiovascular disease. The diet of CKD patients should help to slow the rate of progression of kidney failure, reduce uremic toxicity, decrease proteinuria, maintain good nutritional status, and lower the risk of kidney disease-related secondary complications (cardiovascular disease, bone disease, and hypertension). It has been suggested that plant proteins may exert beneficial effects on blood pressure, proteinuria, and glomerular filtration rate, as well as results in milder renal tissue damage when compared to animal proteins. The National Kidney Foundation recommends vegetarianism, or part-time vegetarian diet as being beneficial to CKD patients. Their recommendations are supported by the results of studies demonstrating that a plant-based diet may hamper the development or progression of some complications of chronic kidney disease, such as heart disease, protein loss in urine, and the progression of kidney damage. However, there are sparse reports suggesting that a vegan diet is not appropriate for CKD patients and those undergoing dialysis due to the difficulty in consuming enough protein and in maintaining proper potassium and phosphorus levels. Therefore, this review will focus on the problem as to whether vegetarian diet and its modifications are suitable for chronic kidney disease patients. PMID:28394274

Vegetarian Diet in Chronic Kidney Disease-A Friend or Foe.

PubMed

Gluba-Brzózka, Anna; Franczyk, Beata; Rysz, Jacek

2017-04-10

Healthy diet is highly important, especially in patients with chronic kidney disease (CKD). Proper nutrition provides the energy to perform everyday activities, prevents infection, builds muscle, and helps to prevent kidney disease from getting worse. However, what does a proper diet mean for a CKD patient? Nutrition requirements differ depending on the level of kidney function and the presence of co-morbid conditions, including hypertension, diabetes, and cardiovascular disease. The diet of CKD patients should help to slow the rate of progression of kidney failure, reduce uremic toxicity, decrease proteinuria, maintain good nutritional status, and lower the risk of kidney disease-related secondary complications (cardiovascular disease, bone disease, and hypertension). It has been suggested that plant proteins may exert beneficial effects on blood pressure, proteinuria, and glomerular filtration rate, as well as results in milder renal tissue damage when compared to animal proteins. The National Kidney Foundation recommends vegetarianism, or part-time vegetarian diet as being beneficial to CKD patients. Their recommendations are supported by the results of studies demonstrating that a plant-based diet may hamper the development or progression of some complications of chronic kidney disease, such as heart disease, protein loss in urine, and the progression of kidney damage. However, there are sparse reports suggesting that a vegan diet is not appropriate for CKD patients and those undergoing dialysis due to the difficulty in consuming enough protein and in maintaining proper potassium and phosphorus levels. Therefore, this review will focus on the problem as to whether vegetarian diet and its modifications are suitable for chronic kidney disease patients.

Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology

PubMed Central

Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

2016-01-01

Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins’ regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. PMID:26123302

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

PubMed Central

Chonchol, Michel; Levi, Moshe

2015-01-01

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. PMID:25287933

Bone metabolism and arterial stiffness after renal transplantation.

PubMed

Cseprekál, Orsolya; Kis, Eva; Dégi, Arianna A; Kerti, Andrea; Szabó, Attila J; Reusz, György S

2014-01-01

To assess the relationship between bone and vascular disease and its changes over time after renal transplantation. Metabolic bone disease (MBD) is common in chronic kidney disease (CKD) and is associated with cardiovascular (CV) disease. Following transplantation (Tx), improvement in CV disease has been reported; however, data regarding changes in bone disease remain controversial. Bone turnover and arterial stiffness (pulse wave velocity (PWV)) were assessed in 47 Tx patients (38 (3-191) months after Tx). Bone alkaline phosphatase (BALP), osteocalcin (OC) and beta-crosslaps were significantly higher in Tx patients, and decreased significantly after one year. There was a negative correlation between BALP, OC and steroid administered (r = -0.35; r = -0.36 respectively). PWV increased in the Tx group (1.15 SD). In patients with a follow up of <24 months, PWV was correlated with BALP and beta-crosslaps (r=0.53; r = 0.69 respectively) while in the ≥24 months group, PWV was correlated with cholesterol (r=0.38). Increased bone turnover and arterial stiffness are present following kidney transplantation. While bone turnover decreases with time, arterial stiffness correlates initially with bone turnover, after which the influence of cholesterol becomes significant. Non-invasive estimation of bone metabolism and arterial stiffness may help to assess CKD-MBD following renal transplantation.

Sex hormones in women with kidney disease.

PubMed

Ahmed, Sofia B; Ramesh, Sharanya

2016-11-01

Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining the role of sex hormones in women with kidney disease are required to address the question. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders.

PubMed

Bover, Jordi; Ureña, Pablo; Aguilar, Armando; Mazzaferro, Sandro; Benito, Silvia; López-Báez, Víctor; Ramos, Alejandra; daSilva, Iara; Cozzolino, Mario

2018-02-14

Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP's with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP's levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.

Recent developments in metabolic bone diseases: a gnathic perspective.

PubMed

Raubenheimer, Erich J; Noffke, Claudia E; Hendrik, Hilde D

2014-12-01

Metabolic bone diseases often are asymptomatic and progress sub clinically. Many patients present at a late stage with catastrophic skeletal and extra skeletal complications. In this article, we provide an overview of normal bone remodeling and a synopsis of recent developments in the following conditions: osteoporosis, rickets/osteomalacia, endocrine-induced bone disease, chronic kidney disease-mineral bone disorder and Paget's disease of bone. Our discussion will emphasize the clinical and microscopic manifestations of these diseases in the jaws.

CXCR6 plays a critical role in angiotensin II-induced renal injury and fibrosis.

PubMed

Xia, Yunfeng; Jin, Xiaogao; Yan, Jingyin; Entman, Mark L; Wang, Yanlin

2014-07-01

Recent studies have shown that angiotensin II (Ang II) plays a critical role in the pathogenesis and progression of hypertensive kidney disease. However, the signaling mechanisms are poorly understood. In this study, we investigated the role of CXCR6 in Ang II-induced renal injury and fibrosis. Wild-type and CXCR6-green fluorescent protein (GFP) knockin mice were treated with Ang II via subcutaneous osmotic minipumps at 1500 ng/kg per minute after unilateral nephrectomy for ≤ 4 weeks. Wild-type and CXCR6-GFP knockin mice had virtually identical blood pressure at baseline. Ang II treatment led to an increase in blood pressure that was similar between wild-type and CXCR6-GFP knockin mice. CXCR6-GFP knockin mice were protected from Ang II-induced renal dysfunction, proteinuria, and fibrosis. CXCR6-GFP knockin mice accumulated fewer bone marrow-derived fibroblasts and myofibroblasts and produced less extracellular matrix protein in the kidneys after Ang II treatment. Furthermore, CXCR6-GFP knockin mice exhibited fewer F4/80(+) macrophages and CD3(+) T cells and expressed less proinflammatory cytokines in the kidneys after Ang II treatment. Finally, wild-type mice engrafted with CXCR6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts, macrophages, and T cells in the kidney after Ang II treatment when compared with wild-type mice engrafted with CXCR6(+/+) bone marrow cells. Our results indicate that CXCR6 plays a pivotal role in the development of Ang II-induced renal injury and fibrosis through regulation of macrophage and T-cell infiltration and bone marrow-derived fibroblast accumulation. © 2014 American Heart Association, Inc.

CXCR6 Plays a Critical Role in Angiotensin II-induced Renal Injury and Fibrosis

PubMed Central

Xia, Yunfeng; Jin, Xiaogao; Yan, Jingyin; Entman, Mark L.; Wang, Yanlin

2014-01-01

Objective Recent studies have shown that angiotensin II (Ang II) plays a critical role in the pathogenesis and progression of hypertensive kidney disease. However, the signaling mechanisms are poorly understood. In this study, we investigated the role of CXCR6 in Ang II-induced renal injury and fibrosis. Approach and Results Wild-type and CXCR6-GFP knockin mice were treated with Ang II via subcutaneous osmotic minipumps at 1500 ng/kg/min after unilateral nephrectomy for up to 4 weeks. WT and CXCR6-GFP knockin mice had virtually identical blood pressure at baseline. Ang II treatment led to an increase in blood pressure that was similar between WT and CXCR6-GFP knockin mice. CXCR6-GFP knockin mice were protected from Ang II-induced renal dysfunction, proteinuria, and fibrosis. CXCR6-GFP knockin mice accumulated fewer bone marrow-derived fibroblasts and myofibroblasts and produced less extracellular matrix protein in the kidneys following Ang II treatment. Furthermore, CXCR6-GFP knockin mice exhibited fewer F4/80+ macrophages and CD3+ T cells and expressed less proinflammatory cytokines in the kidneys after Ang II treatment. Finally, wild-type mice engrafted with CXCR6−/− bone marrow cells displayed fewer bone marrow-derived fibroblasts, macrophages, and T cells in the kidney after Ang II treatment compared with wild-type mice engrafted with CXCR6+/+ bone marrow cells. Conclusions Our results indicate that CXCR6 plays a pivotal role in the development of Ang II-induced renal injury and fibrosis through regulation of macrophage and T cell infiltration and bone marrow-derived fibroblast accumulation. PMID:24855055

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

PubMed Central

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C

2013-01-01

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. PMID:23806280

[The French clinician's guide to the Kidney disease: Improving global outcomes (KDIGO) for chronic kidney disease-mineral and bone disorders (CKD-MBD)].

PubMed

Jean, G; Chazot, C

2010-06-01

The new recommendations of "Kidney disease: improving global outcomes" for the definition and classification of chronic kidney disease and mineral and bone disorders were released in August 2009. We report the most important of these recommendations and a brief comment from a clinician's point of view. The main points to be noted with regard to the new recommendations are as follows: serum calcium should be in the normal range; phosphorus concentration should be lowered toward the normal range and serum parathyroid hormone (PTH) levels should be two to nine times the upper limit of the normal range; bone remodelling can be assessed using alkaline phosphatase; the use of calcium-phosphorus (Ca x P) product as an index is not recommended anymore; at any stage of CKD, vitamin D deficiency and insufficiency must be corrected; vascular calcification should be detected in a simple way using lateral abdominal radiography and echocardiography; a bone biopsy should be performed before therapy with bisphosphonates; the prescription of dialysate calcium should be individualized within the range of 1.25-1.5 mmol/l; the phosphate binder (calcium- or non-calcium-based) and the other treatments for secondary hyperparathyroidism should be individualized based on a global strategy. A majority of these recommendations are not based on evidence and their feasibility and relevance need to be assessed. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Knee Pain in a Renal Transplant Patient

DTIC Science & Technology

2017-04-26

chronic kidney disease. They often develop soft tissue rheumatic syndromes, crystalline arthropathy, and metabolic bone disease. We describe a...hemodialysis. Furthermore, patients who undergo kidney transplant report improvement of symptoms. Disclaimer: The views expressed are those of the author(s

Beta-2 Microglobulin Kidney Disease Test

MedlinePlus

... Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniotic Fluid Analysis Amylase ANCA/MPO/PR3 Antibodies Androstenedione Angiotensin-Converting ... Nitrogen (BUN) BNP and NT-proBNP Body Fluid Analysis Bone Markers Bone Marrow Aspiration and Biopsy BRCA ...

Mineral & Bone Disorder in Chronic Kidney Disease

MedlinePlus

... stages of CKD. Slowed bone growth leads to short stature, which may remain with a child into adulthood. ... and local anesthetic. The health care provider uses imaging techniques such as ultrasound or a computerized tomography ...

Modified Creatinine Index and the Risk of Bone Fracture in Patients Undergoing Hemodialysis: The Q-Cohort Study.

PubMed

Yamada, Shunsuke; Taniguchi, Masatomo; Tokumoto, Masanori; Yoshitomi, Ryota; Yoshida, Hisako; Tatsumoto, Narihito; Hirakata, Hideki; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Hemodialysis patients are at increased risk for bone fracture and sarcopenia. There is close interplay between skeletal muscle and bone. However, it is still unclear whether lower skeletal muscle mass increases the risk for bone fracture. Cross-sectional study and prospective longitudinal cohort study. An independent cohort of 78 hemodialysis patients in the cross-sectional study and 3,030 prevalent patients undergoing maintenance hemodialysis prospectively followed up for 4 years. Skeletal muscle mass measured by bioelectrical impedance analysis (BIA) and modified creatinine index, an estimate of skeletal muscle mass based on age, sex, Kt/V for urea, and serum creatinine level. Bone fracture at any site. In the cross-sectional study, modified creatinine index was significantly correlated with skeletal muscle mass measured by BIA. During a median follow-up of 3.9 years, 140 patients had bone fracture. When patients were divided into sex-specific quartiles based on modified creatinine index, risk for bone fracture estimated by a Fine-Gray proportional subdistribution hazards model with all-cause death as a competing risk was significantly higher in the lower modified creatinine index quartiles (Q1 and Q2) compared to the highest modified creatinine index quartile (Q4) as the reference value in both sexes (multivariable-adjusted HRs for men were 7.81 [95% CI, 2.63-23.26], 5.48 [95% CI, 2.08-14.40], 2.24 [95% CI, 0.72-7.00], and 1.00 [P for trend < 0.001], and for women were 4.44 [95% CI, 1.50-13.11], 2.33 [95% CI, 0.86-6.31], 1.96 [95% CI, 0.82-4.65], and 1.00 [P for trend = 0.007] for Q1, Q2, Q3, and Q4, respectively). One-time assessment of modified creatinine index; no data for residual kidney function and fracture sites and causes. Modified creatinine index was correlated with skeletal muscle mass measured by BIA. Lower modified creatinine index was associated with increased risk for bone fracture in male and female hemodialysis patients. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Genetic engineering of mesenchymal stem cells and its application in human disease therapy.

PubMed

Hodgkinson, Conrad P; Gomez, José A; Mirotsou, Maria; Dzau, Victor J

2010-11-01

The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.

Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).

PubMed

Branham-O'Connor, Melissa; Robichaux, William G; Zhang, Xian-Kui; Cho, Hyeseon; Kehrl, John H; Lanier, Stephen M; Blumer, Joe B

2014-04-11

Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.

Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone

PubMed Central

Lanocha-Arendarczyk, Natalia; Kosik-Bogacka, Danuta I.; Kalisinska, Elzbieta; Sokolowski, Sebastian; Kolodziej, Lukasz; Budis, Halina; Safranow, Krzysztof; Kot, Karolina; Ciosek, Zaneta; Tomska, Natalia; Galant, Katarzyna

2016-01-01

The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone). PMID:27294138

Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone.

PubMed

Lanocha-Arendarczyk, Natalia; Kosik-Bogacka, Danuta I; Kalisinska, Elzbieta; Sokolowski, Sebastian; Kolodziej, Lukasz; Budis, Halina; Safranow, Krzysztof; Kot, Karolina; Ciosek, Zaneta; Tomska, Natalia; Galant, Katarzyna

2016-01-01

The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone).

Neuropathologic findings after organ transplantation. An autopsy study.

PubMed

Schwechheimer, K; Hashemian, A

1995-05-01

Since 1972 organ transplantations of kidney, bone marrow, liver, heart and lung have been performed at the University Hospital of Essen, Germany. Out of 2535 transplantations until September 1993, autopsies were performed in 157 patients In 25 patients (15.9%) neuropathologic findings (n = 26) were found. In 97 autopsies after bone marrow transplantation, 9 patients (9.3%) exhibited a severe neuropathologic alteration. In six patients (6/9; 66.6%), necrotisizing toxoplasmose encephalitis was found. Other cases showed a septic-metastatic mycotic encephalitis with crypto-coccus neoformans and candida albicans (n = 2) and leucemia infiltrates (n = 1). Massive cerebral hemorrhage was the most frequent neuropathologic finding after liver (4/8) and kidney transplantation (3/6). In addition liver-transplanted patients exhibited septic-metastatic encephalitis (3/8) and embolic brain infarct (1/8) as well as cerebral metastases (2/6) and primary malignant cerebral lymphoma in kidney transplantation (1/6). CNS findings in five autopsies after heart-lung-transplantation were diverse. They comprised intracerebral hemorrhage, intravasal lymphoma and septic-metastatic encephalitis, respectively. In summary, neuropathologic autopsy findings after organ transplantation are diverse and preferentially comprise infections, cerebral hemorrhages, and malignant lymphomas. After bone marrow transplantation, the most frequent neuropathologic autopsy finding was toxoplasmose encephalitis and massive cerebral hemorrhages after liver and kidney transplantations.

Histopathological analysis for osteomalacia and tubulopathy in itai-itai disease.

PubMed

Baba, Hayato; Tsuneyama, Koichi; Kumada, Tokimasa; Aoshima, Keiko; Imura, Johji

2014-02-01

Cadmium (Cd) is a widespread environmental contaminant that causes both renal tubulopathy and osteomalacia. Osteomalacia is thought to be a result of renal tubulopathy, but there are few studies about the histopathological relationship between the two pathoses. Therefore, in the present study, we examined specimens from cases of itai-itai disease (IID), the most severe form of chronic cadmium poisoning, to evaluate the relationship between them. We analyzed kidney and bone specimens of 61 IID cases and the data regarding Cd concentration in kidney and bone. Tubulopathy was graded on the basis of a three-step scale (mild, moderate, and severe) using the following three items: the degree of proximal tubular defluxion, thickness of renal cortex, and weight of the kidney. Osteomalacia was evaluated using the relative osteoid volume (ROV). There were 15 cases of mild, 19 cases of moderate, and 27 cases of severe tubulopathy. The average ROV was 24.9 ± 2.0%. ROV tended to increase as tubulopathy advanced in severity, and ROV was significantly higher in cases with severe tubulopathy than those with mild or moderate tubulopathy. ROV had a negative correlation with Cd concentration in the kidney but no correlation with that in the bone. Our results suggest that the development of osteomalacia was related to the development of tubulopathy.

Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation.

PubMed

Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan; O'Neil, John J; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R Neal; Cosimi, A B; Kawai, Tatsuo

2016-01-01

We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more durable mixed chimerism may be necessary for induction of islet allograft tolerance.

Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice.

PubMed

Heveran, Chelsea M; Ortega, Alicia M; Cureton, Andrew; Clark, Ryan; Livingston, Eric W; Bateman, Ted A; Levi, Moshe; King, Karen B; Ferguson, Virginia L

2016-05-01

Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week-old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham surgeries. Mice were fed a normal chow diet and euthanized 11weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60μm of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction was also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD. Copyright © 2016 Elsevier Inc. All rights reserved.

Moderate Chronic Kidney Disease Impairs Bone Quality in C57Bl/6J Mice

PubMed Central

Heveran, Chelsea M.; Ortega, Alicia M.; Cureton, Andrew; Clark, Ryan; Livingston, Eric; Bateman, Ted; Levi, Moshe; King, Karen B.; Ferguson, Virginia L.

2016-01-01

Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham procedures. Mice were fed a normal chow diet and euthanized 11 weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture (μCT) and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60 micrometers of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction were also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD. PMID:26860048

Heart failure and kidney dysfunction: epidemiology, mechanisms and management.

PubMed

Schefold, Joerg C; Filippatos, Gerasimos; Hasenfuss, Gerd; Anker, Stefan D; von Haehling, Stephan

2016-10-01

Heart failure (HF) is a major health-care problem and the prognosis of affected patients is poor. HF often coexists with a number of comorbidities of which declining renal function is of particular importance. A loss of glomerular filtration rate, as in acute kidney injury (AKI) or chronic kidney disease (CKD), independently predicts mortality and accelerates the overall progression of cardiovascular disease and HF. Importantly, cardiac and renal diseases interact in a complex bidirectional and interdependent manner in both acute and chronic settings. From a pathophysiological perspective, cardiac and renal diseases share a number of common pathways, including inflammatory and direct, cellular immune-mediated mechanisms; stress-mediated and (neuro)hormonal responses; metabolic and nutritional changes including bone and mineral disorder, altered haemodynamic and acid-base or fluid status; and the development of anaemia. In an effort to better understand the important crosstalk between the two organs, classifications such as the cardio-renal syndromes were developed. This classification might lead to a more precise understanding of the complex interdependent pathophysiology of cardiac and renal diseases. In light of exceptionally high mortality associated with coexisting HF and kidney disease, this Review describes important crosstalk between the heart and kidney, with a focus on HF and kidney disease in the acute and chronic settings. Underlying molecular and cellular pathomechanisms in HF, AKI and CKD are discussed in addition to current and future therapeutic approaches.

The Biomechanical Testing for the Assessment of Bone Quality in an Experimental Model of Chronic Kidney Disease.

PubMed

Oksztulska-Kolanek, Ewa; Znorko, Beata; Michałowska, Małgorzata; Pawlak, Krystyna

2016-01-01

Mineral metabolism disturbances are common in chronic kidney disease (CKD) and have been classified as a new clinical entity, also known as CKD-mineral and bone disorders (CKD-MBD). A decrease in the bone strength, whose clinical manifestation is a tendency for fracture, has been recognized as an important component of CKD-MBD. Because of ethical issues, measurements of the bone strength in the human body are usually limited to noninvasive techniques, such as radiography, dual-energy X-ray absorptiometry and the assays of bone turnover biomarkers. However, it has been postulated recently that the evidence concerning bone strength based solely on the determination of the bone quantity may be insufficient and that bone quality should also be examined. In this regard, an animal model of CKD can represent an experimental tool to test the effectiveness of new therapeutic strategies. Despite the many available methods that are used to diagnose metabolic bone disorders and predict fracture risk especially in small rodents with CKD, it turns out that the most appropriate are biomechanical tests, which can provide information about the structural and material properties of bone. The present review summarizes and discusses the principles for carrying out selected biomechanical tests (3-point bending test and compression test) and their application in clinical practice. © 2015 S. Karger AG, Basel.

Establishment of Donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

DTIC Science & Technology

2016-09-01

specific immunosuppression. Induction of tolerance to the CTA is the ideal solution. Combined mixed allogeneic chimerism induction and kidney ...transplantation has been shown to induce robust tolerance to the kidney allograft despite transient mixed chimerism in non-human primates and humans...solution. Mixed chimerism induction via hematopoietic cell transplantation (HCT) has been shown to facilitate tolerance induction to kidney allografts

Bisphosphonates and Bone Fractures in Long-term Kidney Transplant Recipients

PubMed Central

Conley, Emily; Muth, Brenda; Samaniego, Millie; Lotfi, Mary; Voss, Barbara; Armbrust, Mike; Pirsch, John; Djamali, Arjang

2013-01-01

Background There is little information on the role of bisphosphonates and bone mineral density (BMD) measurements for the follow-up and management of bone loss and fractures in long-term kidney transplant recipients. Methods To address this question, we retrospectively studied 554 patients who had two BMD measurements after the first year posttransplant and compared outcomes in patients treated, or not with bisphosphonates between the two BMD assessments. Kaplan-Meier survival and stepwise Cox regression analyses were performed to examine fracture-free survival rates and the risk-factors associated with fractures. Results The average time (±SE) between transplant and the first BMD was 1.2±0.05 years. The time interval between the two BMD measurements was 2.5±0.05 years. There were 239 and 315 patients in the no-bisphosphonate and bisphosphonate groups, respectively. Treatment was associated with significant preservation of bone loss at the femoral neck (HR 1.56, 95% CI 1.21-2.06, P=0.0007). However, there was no association between bone loss at the femoral neck and fractures regardless of bisphosphonate therapy. Stepwise Cox regression analyses showed that type-1 diabetes, baseline femoral neck T-score, interleukin-2 receptor blockade, and proteinuria (HR 2.02, 0.69, 0.4, 1.23 respectively, P<0.01), but not bisphosphonates, were associated with the risk of fracture. Conclusions Bisphosphonates may prevent bone loss in long-term kidney transplant recipients. However, these data suggest a limited role for the initiation of therapy after the first posttransplant year to prevent fractures. PMID:18645484

Rictor/mammalian target of rapamycin complex 2 promotes macrophage activation and kidney fibrosis.

PubMed

Ren, Jiafa; Li, Jianzhong; Feng, Ye; Shu, Bingyan; Gui, Yuan; Wei, Wei; He, Weichun; Yang, Junwei; Dai, Chunsun

2017-08-01

Mammalian target of rapamycin (mTOR) signalling controls many essential cellular functions. However, the role of Rictor/mTOR complex 2 (mTORC2) in regulating macrophage activation and kidney fibrosis remains largely unknown. We report here that Rictor/mTORC2 was activated in macrophages from the fibrotic kidneys of mice. Ablation of Rictor in macrophages reduced kidney fibrosis, inflammatory cell accumulation, macrophage proliferation and polarization after unilateral ureter obstruction or ischaemia/reperfusion injury. In bone marrow-derived macrophages (BMMs), deletion of Rictor or blockade of protein kinase Cα inhibited cell migration. Additionally, deletion of Rictor or blockade of Akt abolished interleukin-4-stimulated or transforming growth factor (TGF)-β1-stimulated macrophage M2 polarization. Furthermore, deletion of Rictor downregulated TGF-β1-stimulated upregulation of multiple profibrotic cytokines, including platelet-derived growth factor, vascular endothelial growth factor and connective tissue growth factor, in BMMs. Conditioned medium from TGF-β1-pretreated Rictor -/- macrophages stimulated fibroblast activation less efficiently than that from TGF-β1-pretreated Rictor +/+ macrophages. These results demonstrate that Rictor/mTORC2 signalling can promote macrophage activation and kidney fibrosis. Targeting this signalling pathway in macrophages may shine light on ways to protect against kidney fibrosis in patients with chronic kidney diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Erythropoietin as a novel brain and kidney protective agent.

PubMed

Moore, E M; Bellomo, R; Nichol, A D

2011-05-01

Erythropoietin is a 30.4 kDa glycoprotein produced by the kidney, which is mostly known for its physiological function in regulating red blood cell production in the bone marrow Accumulating evidence, however suggests that erythropoietin has additional organ protective effects, which may specifically be useful in protecting the brain and kidneys from injury. Experimental evidence suggests that these protective mechanisms are multi-factorial in nature and may include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways and promotion of recovery. In this article we review the physiology of erythropoietin, assess previous work that supports the role of erythropoietin as a general tissue protective agent and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on specific laboratory and clinical data that suggest that erythropoietin has a strong brain protective and kidney protective effect. In addition, we comment on the implications of these studies for clinicians at the bedside and for researchers designing controlled trials to further elucidate the true clinical utility of erythropoietin as a neuroprotective and nephroprotective agent. Finally, we describe EPO-TBI, a double-blinded multi-centre randomised controlled trial involving the authors that is being conducted to investigate the organ protective effects of erythropoietin on the brain, and also assesses its effect on the kidneys.

Renal control of calcium, phosphate, and magnesium homeostasis.

PubMed

Blaine, Judith; Chonchol, Michel; Levi, Moshe

2015-07-07

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. Copyright © 2015 by the American Society of Nephrology.

Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology.

PubMed

Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

2015-01-01

Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins' regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. © 2015 Elsevier Inc. All rights reserved.

A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D3 activation.

PubMed

Meyer, Mark B; Benkusky, Nancy A; Kaufmann, Martin; Lee, Seong Min; Onal, Melda; Jones, Glenville; Pike, J Wesley

2017-10-20

The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D 3 to its hormonal form, 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1 , are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH) 2 D 3 -mediated regulation of Cyp27b1 expression. Selective genomic deletion of key components within this module in mice resulted in loss of either PTH induction or FGF23 and 1,25(OH) 2 D 3 suppression of Cyp27b1 gene expression; the former loss caused a debilitating skeletal phenotype, whereas the latter conferred a quasi-normal bone mineral phenotype through compensatory homeostatic mechanisms involving Cyp24a1 We found that Cyp27b1 is also expressed at low levels in non-renal cells, in which transcription was modulated exclusively by inflammatory factors via a process that was unaffected by deletion of the kidney-specific module. These results reveal that differential regulation of Cyp27b1 expression represents a mechanism whereby 1,25(OH) 2 D 3 can fulfill separate functional roles, first in the kidney to control mineral homeostasis and second in extra-renal cells to regulate target genes linked to specific biological responses. Furthermore, we conclude that these mouse models open new avenues for the study of vitamin D metabolism and its involvement in therapeutic strategies for human health and disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

PubMed Central

Campbell, Preston; Ma, Yun

2013-01-01

The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on β-adrenergic receptor (βAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and βAR signaling in the regulation of skeletal homeostasis. PMID:23765388

Role of Bone Marrow Derived Mesenchymal Stem Cells and the Protective Effect of Silymarin in Cisplatin-Induced Acute Renal Failure in Rats.

PubMed

Ibrahim, Mohamed El-Tantawy; Bana, Eman El; El-Kerdasy, Hanan I

2018-01-01

Cisplatin is a highly effective antitumor agent whose clinical application is limited by its nephrotoxicity, which is associated with high mortality and morbidity rates. We aimed to study the protective role of silymarin and mesenchymal stem cells as a therapeutic tool of cisplatin nephrotoxicity. We injected rats with cisplatin in a dose of 5mg/kg body weight for 5 days to induce acute renal failure (ARF). Silymarin was administrated 6 hours before cisplatin injection and mesenchymal stem cells were injected 24 hours after cisplatin-induced ARF. We assessed the ARF biochemically by elevation of kidney function tests and histopathologically by an alteration of the histological architecture of the renal cortex in the form of shrinkage of glomeruli, lobulated tufts and glomerular hypertrophy with narrowing capsular space. The tubules showed extensive tubular degeneration with cellular hyaline materials and debris in the lumen of the renal tubules. The renal blood vessels appeared sclerotic with marked thickened walls. When silymarin was given in different doses before cisplatin, it decreased the toxic effect of cisplatin in the kidney but sclerotic blood vessels remained. Injection of mesenchymal stem cells in rats with cisplatin-induced ARF improved the histopathological effects of cisplatin in renal tissues and kidney function tests were significantly improved. There was a significant improvement in kidney function tests and renal histopathology by using silymarin as protective mechanism in cisplatin-induced ARF. Administration of mesenchymal stem cells denoted a more remarkable therapeutic effect in ARF. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Increased bone morphogenetic protein 7 signalling in the kidneys of dogs affected with a congenital portosystemic shunt.

PubMed

van Dongen, Astrid M; Heuving, Susanne M; Tryfonidou, Marianna A; van Steenbeek, Frank G; Rothuizen, Jan; Penning, Louis C

2015-05-01

Dogs with a congenital portosystemic shunt (CPSS) often have enlarged and hyper-filtrating kidneys. Although expression of different growth factors has been well-described in the livers of dogs affected with a CPSS, their expression in the kidneys has yet to be determined. Bone morphogenetic protein 7 (BMP-7), hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β have been implicated in renal development (BMP-7, HGF) or the onset of renal fibrosis (TGF-β). Moreover, BMP-7 and HGF have protective properties in renal fibrosis. In this study, the expression and activity of BMP-7 were investigated in renal biopsies obtained from 13 dogs affected with a CPSS and compared to similar samples from age-matched healthy control dogs. Both quantitative reverse-transcriptase PCR and Western blotting showed up-regulated BMP-7 signalling in kidneys of CPPS-affected dogs. These research findings may help to explain the renal pathology/dysfunction in dogs affected with a CPSS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bone Genes in the Kidney of Stone Formers

NASA Astrophysics Data System (ADS)

Evan, Andrew P.; Bledsoe, Sharon B.

2008-09-01

Intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate stone formers (ICSF) have revealed a distinct pattern of mineral deposition in the interstitium of the renal papilla. The earliest sites of these deposits, termed Randall's plaque, are found in the basement membrane of thin loops of Henle and appear to spread into the surrounding interstitium down to the papillary epithelium. Recent studies show kidney stones of ICSF patients grow attached to the renal papilla and at sites of Randall's plaque. Together these observations suggest that plaque formation may be the critical step in stone formation. In order to control plaque formation and thereby reduce future kidney stone development, the mechanism of plaque deposition must be understood. Because the renal papilla has unique anatomical features similar to bone and the fact that the interstitial deposits of ICSF patients are formed of biological apatite, this paper tests the hypothesis that sites of interstitial plaque form as a result of cell-mediated osteoblast-like activity.

Ectopic bone formation cannot occur by hydroxyapatite/β-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice

NASA Astrophysics Data System (ADS)

Cheng, Lijia; Duan, Xin; Xiang, Zhou; Shi, Yujun; Lu, Xiaofeng; Ye, Feng; Bu, Hong

2012-12-01

Many studies have shown that calcium phosphate ceramics (CP) have osteoconductive and osteoinductive properties; however, the exact mechanism of bone induction has not yet been reported. This study was performed to investigate if destroying immunological function will influence osteogenesis, to explain the mechanism which is unclear. In this study, twenty C57BL/6 mice were divided into two groups (n = 10), in group 1, a hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramic was implanted into both the left and right leg muscles of each mouse; in group 2, ten mice experienced lethal irradiation, then were injected bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice by tail veil, after bone marrow transplantation (BMT), heart, liver, spleen, lung, kidney, and muscle were harvested for biological analysis, after the GFP chimera model was established successfully, the same HA/β-TCP ceramic was implanted into both leg muscles of each mouse immediately after irradiation. 45 and 90 days after implantation, the ceramics of the two groups were harvested to perform with hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining; the results showed that there was no bone formation in group 2, while new bone tissues were detected in group 1. Our findings suggest that the BM cell from GFP transgenic mice is a good biomarker and it could set a good platform for chimera model; it also shows that BM cell is one of cell resources of bone induction, and destruction of immune function will impede osteoinduction by CP. Overall, our results may shed light on clear mechanism study of bone induction in the future.

Effects of chytridiomycosis on hematopoietic tissue in the spleen, kidney and bone marrow in three diverse amphibian species.

PubMed

Brannelly, Laura A; Webb, Rebecca J; Skerratt, Lee F; Berger, Lee

2016-10-01

One of the major causes of amphibian population decline is the deadly fungal pathogen Batrachochytrium dendrobatidis, Bd Research on pathogenesis and host immunity aims to inform development of targeted conservation interventions. Studies examining global host immune responses as well as effects on lymphocytes in vitro suggest that Bd infection causes immunosuppression. However, it is unknown which hematopoietic tissues are affected and if these effects differ among host species. We investigated the effect of experimental Bd infection on three diverse amphibian species by quantifying the amount of hematopoietic tissue in the spleen, bone marrow and kidney. Upon Bd infection, hematopoietic tissue in the kidney tended to be depleted, while the spleen appeared unaffected. The bone marrow in highly susceptible species was depleted, whereas an increase in hematopoietic tissue was observed in the more resistant species. Our study demonstrates that species and hematopoietic tissues behave differently in response to Bd infection, and may be related to the species' susceptibility to infection. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Expression of bone morphogenetic proteins 4, 6 and 7 is downregulated in kidney allografts with interstitial fibrosis and tubular atrophy.

PubMed

Furic-Cunko, Vesna; Kes, Petar; Coric, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Basic-Jukic, Nikolina

2015-07-01

Bone morphogenetic proteins (BMPs) are pleiotropic growth factors. This paper investigates the connection between the expression pattern of BMPs in kidney allograft tissue versus the cause of allograft dysfunction. The expression pattern of BMP2, BMP4, BMP6 and BMP7 in 50 kidney allografts obtained by transplant nephrectomy is investigated. Immunohistochemical staining is semiquantitatively evaluated for intensity to identify the expression pattern of BMPs in normal and allograft kidney tissues. The expression of BMP4 is unique between different tubular cell types in grafts without signs of fibrosis. This effect is not found in specimens with high grades of interstitial fibrosis and tubular atrophy (IFTA). In samples with IFTA grades II and III, the BMP7 expression is reduced in a significant fraction of specimens relative to those without signs of IFTA. The expression pattern of BMP6 indicates that its activation may be triggered by the act of transplantation and subsequent reperfusion injury. The expression of BMP2 is strong in all types of tubular epithelial cells and does not differ between the compared allografts and control kidney specimens. The intensity and expression pattern of BMP4, BMP6 and BMP7 in transplanted kidney tissue are found to be dependent upon the length of the transplanted period, the clinical indication for transplant nephrectomy and signs of IFTA in kidney tissue.

The Effect of Naturally Occurring Chronic Kidney Disease on the Micro-Structural and Mechanical Properties of Bone

PubMed Central

Meltzer, Hagar; Milrad, Moran; Brenner, Ori; Atkins, Ayelet; Shahar, Ron

2014-01-01

Chronic kidney disease (CKD) is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies) or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD). Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD. PMID:25333360

The effect of the Syrian crisis on organ transplantation in Syria.

PubMed

Saeed, Bassam

2015-04-01

The war in Syria that started in March 2011 has destroyed much of the country's infrastructure including many hospitals. The total number of kidney transplants performed in Syria in 2010 was 385 transplants before the number gradually declined to 154 transplants in 2013, a decrease of 60%. In addition, the number of operational kidney transplant centers has decreased from 8 to 4 centers. Unrelated-donor kidney transplant decreased from 70% during the years that preceded the crisis to 47% in 2013. More than 50% of physicians and surgeons involved in kidney transplant are not practicing transplant currently in their centers. Difficulties in the provision of immunosuppressive drugs for all patients in all provinces constitute a major challenge for the health authorities and transplant patients, especially patients who cannot arrange an alternate source. The project to initiate liver transplant came to a halt because foreign trainers could not visit Syria. The autologous bone marrow transplant program continued to function, but in a smaller and irregular manner. The commitment of transplant teams despite the large challenges was, and still is, extraordinary. In conclusion, all aspects of organ transplant have been affected, paralyzing new projects and negatively affecting existing programs.

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

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

Cheng, Kang; Rai, Partab; Lan, Xiqian

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic micemore » and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.« less

EFFECTS OF LINDANE AND LINURON ON CALCIUM METABOLISM, MORPHOMETRY, AND THE KIDNEY

EPA Science Inventory

The effects of lindane and linuron on calcium metabolism, bone morphometry and the kidney. xperiments were performed to investigate the effects of lindane and linuron on calcium metabolism, femur morphometry and nephrotoxicity. ong-Evans hooded rats were dosed daily for 10 weeks ...

Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

PubMed Central

Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

2016-01-01

The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. PMID:27466399

Bone pulsating metastasis due to renal cell carcinoma.

PubMed

Cınar, Murat; Derincek, Alihan; Karan, Belgin; Akpınar, Sercan; Tuncay, Cengiz

2010-11-01

Pulsation on the bone cortex surface is a rare condition. Pulsative palpation of the superficial-located bone tumors can be misperceived as an aneurysm. Fifty-eight-year-old man is presented with pulsating bone mass in his proximal tibia. During angiographic examination, hypervascular masses were diagnosed both at right kidney and at right proximal tibia. Renal cell carcinoma was diagnosed after abdominal CT scan. Proximal tibia biopsy was complicated with projectile bleeding.

Racial differences in kidney function among individuals with obesity and metabolic syndrome: results from the Kidney Early Evaluation Program (KEEP).

PubMed

Bomback, Andrew S; Kshirsagar, Abhijit V; Whaley-Connell, Adam T; Chen, Shu-Cheng; Li, Suying; Klemmer, Philip J; McCullough, Peter A; Bakris, George L

2010-03-01

Obesity and metabolic syndrome may differ by race. For participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP), we examined whether African American and white participants with obesity and metabolic syndrome differ regarding albuminuria, estimated glomerular filtration rate (eGFR), anemia, and bone/mineral metabolism derangements in chronic kidney disease (CKD). 3 study cohorts were assembled: (1) eligible African American and white KEEP participants with body mass index > or = 30 kg/m(2), (2) a subgroup meeting criteria for metabolic syndrome, and (3) a subgroup with eGFR < 60 mL/min/1.73 m(2) and laboratory measurements for hemoglobin, parathyroid hormone, calcium, and phosphorus. Patient characteristics and kidney function assessments were compared and tested using chi(2) (categorical variables) and t test (continuous variables). Univariate and multivariate logistic regression analyses were performed to evaluate associations of race with kidney disease measures. Of 37,107 obese participants, 48% were African American and 52% were white. Whites were more likely to have metabolic syndrome components (hypertension, 87.1% vs 84.8%; dyslipidemia, 81.6% vs 66.7%; diabetes, 42.7% vs 34.9%) and more profoundly decreased eGFR than African Americans (CKD stages 3-5 prevalence, 23.6% vs 13.0%; P < 0.001). African Americans were more likely to have abnormal urinary albumin excretion (microalbuminuria, 12.5% vs 10.2%; OR, 1.60 [95% CI, 1.45-1.76]; macroalbuminuria, 1.3% vs 1.2%; OR, 1.61 [95% CI, 1.23-2.12]) and CKD stages 1-2 (10.3% vs 7.1%; OR, 1.54 [95% CI, 1.38-1.72]). For participants with CKD stages 3-5, anemia prevalence was 32.4% in African Americans and 14.1% in whites; corresponding values for secondary hyperparathyroidism were 66.2% and 46.6%, respectively. Obesity and metabolic syndrome may be heterogeneous disease states in African Americans and whites, possibly explaining differences in long-term kidney and cardiovascular outcomes. Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Bone Sialoproteins and Breast Cancer Detection

DTIC Science & Technology

2004-07-01

used to follow proteolytic activity on more natural macromolecular substrates. These substrates are so highly substituted with fluorescein moieties that...uninformative for breast cancer, but does correlate with bone mineral density, parathyroid hormone and phosphorus . (Summary of Appendix II). Normal MEPE...calcium, phosphorus , vitamin D, as well as novel phosphatonin(s), and the bone and kidney organs. Candidate phosphaturic factors include MEPE; PHEX, a

42 CFR 121.13 - Definition of human organ under section 301 of the National Organ Transplant Act of 1984, as...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 1984, as amended, means the human (including fetal) kidney, liver, heart, lung, pancreas, bone marrow, cornea, eye, bone, skin, intestine (including the esophagus, stomach, small and/or large intestine, or...

42 CFR 121.13 - Definition of human organ under section 301 of the National Organ Transplant Act of 1984, as...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 1984, as amended, means the human (including fetal) kidney, liver, heart, lung, pancreas, bone marrow, cornea, eye, bone, skin, intestine (including the esophagus, stomach, small and/or large intestine, or...

Metabolic and biochemical considerations of bone.

PubMed

Lutwak, L

1975-01-01

Recognition of the dynamic aspects of bone metabolism can lead to a unified concept involving endocrine and nutritional influences. Although most hormones can influence bone metabolism directly or indirectly, the principal ones involved in skeletal metabolism are parathyroid hormone, calcitonin and 1,25-dihydroxy-vitamin D. The actions of parathyroid hormone and 1,25-dihydroxy-vitamin D result in elevations of circulating extracellular fluid calcium concentration through actions directly on bone, intestine, and kidney. Calcitonin leads to decreases in calcium concentration, primarily by action on bone and kidney. The absorption and retention of calcium by the organism is further influenced by the dietary content of calcium, phosphorus, protein, and fluoride. Chronic dietary deficiencies of calcium and excesses of phosphorus may lead to chronic nutritional secondary hyperparathyroidism with resulting skeletal demineralization. In both experimental animals and in man, the earliest manifestation of this condition may be demineralization of the jaw with resultant paradentosis. Experimental studies in animals and in man have shown that this form of demineralization may be completely reversed by increasing dietary calcium and decreasing dietary phosphrous.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

PubMed

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Can bone marrow differentiate into renal cells?

PubMed

Imai, Enyu; Ito, Takahito

2002-10-01

A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

Effect of a Gonadotrophin-Releasing Hormone Analogue on Lung Function in Lymphangioleiomyomatosis

PubMed Central

Harari, Sergio; Cassandro, Roberto; Chiodini, Jacopo; Taveira-DaSilva, Angelo M.; Moss, Joel

2010-01-01

Background Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM. Methods Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed. Results Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density. Conclusions Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density. PMID:18071009

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

PubMed Central

Pawlak, Krystyna; Oksztulska-Kolanek, Ewa; Domaniewski, Tomasz; Znorko, Beata; Karbowska, Malgorzata; Citkowska, Aleksandra; Rogalska, Joanna; Roszczenko, Alicja; Brzoska, Malgorzata M.; Pawlak, Dariusz

2017-01-01

Background Disturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD. Methods Thirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites. Results Subtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry. Discussion In addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD. PMID:28439468

Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome.

PubMed

Tanaka, Mari; Asada, Misako; Higashi, Atsuko Y; Nakamura, Jin; Oguchi, Akiko; Tomita, Mayumi; Yamada, Sachiko; Asada, Nariaki; Takase, Masayuki; Okuda, Tomohiko; Kawachi, Hiroshi; Economides, Aris N; Robertson, Elizabeth; Takahashi, Satoru; Sakurai, Takeshi; Goldschmeding, Roel; Muso, Eri; Fukatsu, Atsushi; Kita, Toru; Yanagita, Motoko

2010-03-01

The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3-/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

Preparation, Biological Evaluation and Dosimetry Studies of 175Yb-Bis-Phosphonates for Palliative Treatment of Bone Pain.

PubMed

Fakhari, Ashraf; Jalilian, Amir R; Yousefnia, Hassan; Shanehsazzadeh, Saeed; Samani, Ali Bahrami; Daha, Fariba Johari; Ardestani, Mehdi Shafiee; Khalaj, Ali

2015-10-05

Optimized production and quality control of ytterbium-175 (Yb-175) labeled pamidronate and alendronate complexes as efficient agents for bone pain palliation has been presented. Yb-175 labeled pamidronate and alendronate (175Yb-PMD and 175Yb-ALN) complexes were prepared successfully at optimized conditions with acceptable radiochemical purity, stability and significant hydroxyapatite absorption. The biodistribution of complexes were evaluated up to 48 h, which demonstrated significant bone uptake ratios for 175Yb-PAM at all-time intervals. It was also detected that 175Yb-PAM mostly washed out and excreted through the kidneys. The performance of 175Yb-PAM in an animal model was better or comparable to other 175Yb-bone seeking complexes previously reported. Based on calculations, the total body dose for 175Yb-ALN is 40% higher as compared to 175Yb-PAM (especially kidneys) indicating that 175Yb-PAM is probably a safer agent than 175Yb-ALN.

Preparation, Biological Evaluation and Dosimetry Studies of 175Yb-Bis-Phosphonates for Palliative Treatment of Bone Pain

PubMed Central

Fakhari, Ashraf; Jalilian, Amir R.; Yousefnia, Hassan; Shanehsazzadeh, Saeed; Samani, Ali Bahrami; Daha, Fariba Johari; Ardestani, Mehdi Shafiee; Khalaj, Ali

2015-01-01

Objective: Optimized production and quality control of ytterbium-175 (Yb-175) labeled pamidronate and alendronate complexes as efficient agents for bone pain palliation has been presented. Methods: Yb-175 labeled pamidronate and alendronate (175Yb-PMD and 175Yb-ALN) complexes were prepared successfully at optimized conditions with acceptable radiochemical purity, stability and significant hydroxyapatite absorption. The biodistribution of complexes were evaluated up to 48 h, which demonstrated significant bone uptake ratios for 175Yb-PAM at all-time intervals. It was also detected that 175Yb-PAM mostly washed out and excreted through the kidneys. Results: The performance of 175Yb-PAM in an animal model was better or comparable to other 175Yb-bone seeking complexes previously reported. Conclusion: Based on calculations, the total body dose for 175Yb-ALN is 40% higher as compared to 175Yb-PAM (especially kidneys) indicating that 175Yb-PAM is probably a safer agent than 175Yb-ALN. PMID:27529886

Prevalence and risk factors for nonvertebral bone fractures in kidney transplant recipients - a single-center retrospective analysis.

PubMed

Jerman, Alexander; Lindič, Jelka; Škoberne, Andrej; Borštnar, Špela; Martinuč Bergoč, Maja; Godnov, Uroš; Kovač, Damjan

Complex and longstanding bone disease superimposed by harmful influences of immunosuppression is the reason for increased risk of bone fracture in kidney transplant recipients. The aim of our study was to analyze the incidence and prevalence of nonvertebral bone fractures and early (in the first post-transplant year) clinical and laboratory risk factors for suffering bone fracture in the long-term post-transplant period. Clinical and laboratory data as well as bone mineral density (BMD) measurements of 507 first kidney transplant recipients who were transplanted in the period from 1976 to 2011 were analyzed. The mean age of included patients was 54.3 ± 12.0 years, there were 45% females, and mean time on renal replacement treatment prior to transplantation was 63.4 ± 43.6 months. The average observation time post-transplant was 9.7 years (1.4 - 36.3 years). Post-transplant, 64 (12.6%) patients suffered 89 nonvertebral fractures (44 patients suffered 1 fracture, 15 patients 2 fractures, and 5 patients 3 fractures). Patients with fractures had significantly lower late BMD of femoral neck in the period of 1 - 10 years post-transplant, had osteopenia and osteoporosis more frequently in the same time period, and higher serum alkaline phosphatase in the first year post-transplant. 13 patients (13/64, 20.3%) had major fractures. Patients with major fractures were significantly older than patients with no major fractures and had lower serum albumin. Frequency of treatment with bisphosphonate, calcium, or phosphate did not differ between the groups. Vitamin D supplement (active form in 98% of cases) was prescribed more frequently in the group without fractures, but this was not statistically significant. Fracture rate in our transplant patient population was comparable to that reported in the literature. Except for a higher level of serum total alkaline phosphatase in the fracture group, we found no other early laboratory risk factors for bone fractures. BMD at the femoral region 1 - 10 years after kidney transplantation but not BMD at the time of transplantation was a risk factor for nonvertebral fractures. Osteopenia and osteoporosis in the post-transplant period were found to be a fracture risk factor.
.

Colchicine intoxication in familial Mediterranean fever patients using clarithromycin for the treatment of Helicobacter pylori: a series of six patients.

PubMed

Haj Yahia, Soad; Ben Zvi, Ilan; Livneh, Avi

2018-01-01

Familial Mediterranean fever is a hereditary disease, characterized by recurrent episodes of inflammation. Colchicine, the mainstay of therapy, is administered continuously to all diagnosed FMF patients. Drug-drug interaction between colchicine and clarithromycin, resulting in colchicine intoxication, has been noted, mainly in association with gout and pneumonia. In FMF, this adverse event has been scarcely described. We present and characterize six patients with clarithromycin-related colchicine intoxication, aiming mainly at characterizing the FMF-specific features of this event. This study is a retrospective analysis, based on clinical and hospital records of all FMF patients admitted to one hospital during 2002-2015, for colchicine intoxication, precipitated by consumption of clarithromycin. All six patients were women who received colchicine for FMF, and clarithromycin for Helicobacter pylori (HBP) gastric infection. Their daily dosages of colchicine ranged from 1.5 to 2.5 mg. Two had mild FMF, two moderate and two severe diseases. Colchicine intoxication occurred despite intact kidney function and was characterized by abdominal pain, diarrhea, weakness, rhabdomyolysis, hepatitis, kidney impairment and bone marrow injury. It is concluded that clarithromycin-induced colchicine intoxication is a hazard in FMF. It occurs despite normal kidney function and standard colchicine dose and is associated with female sex and moderate to severe FMF.

Effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism.

PubMed

Borrego Utiel, Francisco José; Bravo Soto, Juan Antonio; Merino Pérez, María José; González Carmelo, Isabel; López Jiménez, Verónica; García Álvarez, Teresa; Acosta Martínez, Yelenei; Mazuecos Blanca, María Auxiliadora

2015-01-01

Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period. A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/ml; 6 months 226 ± 184 pg/ml; 12 months 207 ± 120; 24 months 193 ± 119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/l; 6 months 85 ± 36 IU/l, 12 months 81 ± 39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar. Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

In search of adult renal stem cells.

PubMed

Anglani, F; Forino, M; Del Prete, D; Tosetto, E; Torregrossa, R; D'Angelo, A

2004-01-01

The therapeutic potential of adult stem cells in the treatment of chronic degenerative diseases has becoming increasingly evident over the last few years. Significant attention is currently being paid to the development of novel treatments for acute and chronic kidney diseases too. To date, promising sources of stem cells for renal therapies include adult bone marrow stem cells and the kidney precursors present in the early embryo. Both cells have clearly demonstrated their ability to differentiate into the kidney's specialized structures. Adult renal stem cells have yet to be identified, but the papilla is where the stem cell niche is probably located. Now we need to isolate and characterize the fraction of papillary cells that constitute the putative renal stem cells. Our growing understanding of the cellular and molecular mechanisms behind kidney regeneration and repair processes - together with a knowledge of the embryonic origin of renal cells - should induce us, however, to bear in mind that in the kidney, as in other mesenchymal tissues, the need for a real stem cell compartment might be less important than the phenotypic flexibility of tubular cells. Thus, by displaying their plasticity during kidney maintenance and repair, terminally differentiated cells may well function as multipotent stem cells despite being at a later stage of maturation than adult stem cells. One of the major tasks of Regenerative Medicine will be to disclose the molecular mechanisms underlying renal tubular plasticity and to exploit its biological and therapeutic potential.

Phosphate-a poison for humans?

PubMed

Komaba, Hirotaka; Fukagawa, Masafumi

2016-10-01

Maintenance of phosphate balance is essential for life, and mammals have developed a sophisticated system to regulate phosphate homeostasis over the course of evolution. However, due to the dependence of phosphate elimination on the kidney, humans with decreased kidney function are likely to be in a positive phosphate balance. Phosphate excess has been well recognized as a critical factor in the pathogenesis of mineral and bone disorders associated with chronic kidney disease, but recent investigations have also uncovered toxic effects of phosphate on the cardiovascular system and the aging process. Compelling evidence also suggests that increased fibroblastic growth factor 23 and parathyroid hormone levels in response to a positive phosphate balance contribute to adverse clinical outcomes. These insights support the current practice of managing serum phosphate in patients with advanced chronic kidney disease, although definitive evidence of these effects is lacking. Given the potential toxicity of excess phosphate, the general population may also be viewed as a target for phosphate management. However, the widespread implementation of dietary phosphate intervention in the general population may not be warranted due to the limited impact of increased phosphate intake on mineral metabolism and clinical outcomes. Nonetheless, the increasing incidence of kidney disease or injury in our aging society emphasizes the potential importance of this issue. Further work is needed to more completely characterize phosphate toxicity and to establish the optimal therapeutic strategy for managing phosphate in patients with chronic kidney disease and in the general population. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Parathyroid Hormone and Bone in Dialysis Patients.

PubMed

Kazama, Junichiro James; Wakasugi, Minako

2018-06-01

Bone maintains extracellular calcium levels through a system called bone remodeling. Parathyroid hormone (PTH) is the major initiator of this system, which is secreted by the information through calcium sensing receptor in parathyroid cells. PTH modifies calcified bone morphology through a process of its bone action. Therefore, extremely hyperactivated parathyroid function seen in patients with chronic kidney disease has been considered to have a negative impact on the bone mechanical properties. While skeletal deformities and fragility fractures were common among dialysis patients up to the 1970s, after which methods for the treatment of hyperparathyroidism were developed, we now seldom encounter those cases with severe secondary hyperparathyroidism in Japan. In a three-dimensional morphometry of biopsied iliac bone samples obtained from dialysis patients, PTH level was inversely correlated with cortical bone thickness, however, this relationship disappeared among those with intact PTH < 1000 pg/mL. Higher PTH levels were associated with more complicated and irregular cancellous bone surface, but this change was not accompanied with decreased cancellous bone connectivity. These findings theoretically support the recent clinical study results that PTH levels no longer show a tight correlation with fracture risk in dialysis patients. Nevertheless, the use of calcium sensing receptor agonist is likely to be associated with reduced hip fracture risk in dialysis patients. Further study is needed to reveal its pharmacological mechanism on bone. © 2018 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

[Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Necessity of bone biopsy].

PubMed

Ito, Akemi; Yajima, Aiji

2011-09-01

Histological analysis of undecalcified bone biopsy specimens is a valuable clinical and research tool for studying the etiology, pathogenesis and treatment of metabolic bone diseases. In case of osteoporosis, bone biopsy is not usually required for the diagnosis ; however, bone histomorphometry may be useful in rare cases with unusual skeletal fragility. Bone histomorphometry also provides valuable information on the mechanism of action, safety and efficacy of new anti-osteoporosis drugs. Bone histomorphometry is useful for the diagnosis and the assessment of treatment response in rickets/osteomalacia and in CKD-MBD (chronic kidney disease-mineral and bone disorders) . In Japan, bone biopsy is often performed to establish the diagnosis of Paget's disease of bone, especially to differentiate it from metastatic bone disease.

The Role of Calcium in Osteoporosis

NASA Technical Reports Server (NTRS)

Arnaud, C. D.; Sanchez, S. D.

1991-01-01

Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

[CIP and CAP fragments of parathormone and selected parameters of calcium-phosphate balance in patients with chronic kidney disease treated with repeated haemodialysis].

PubMed

Polak-Jonkisz, Dorota; Zwolińska, Danuta; Nahaczewska, Wiesława

2010-01-01

Chronic kidney disease (CKD) leads to bone and mineral complications, which are manifested, among others, by hyperparathyroidism, calcium-phosphate and vitamin D balance disturbances. The results of investigation assessing the usefulness of CAP/CIP ratio, (cyclase activating PTH/cyclase inactive PTH) as a marker of bone turnover and bone disturbances in this group of patients are contradictory. was to estimate the concentration of CAP and CIP of parathormone, connection with selected calcium-phosphate balance parameters and usefulness of CAP/CIP ratio to differentiate bone mineral density in patients with CKD treated with repeated haemodialysis. The study included 31 children aged 5 to 18 years. Group I - 15 haemodialysed children. Group II - 16 healthy children. The patients underwent the following serum measurements: calcium concentration (Ca), inorganic phosphate (P), 1.25-dihydroxyvitamin D, parathormone (intact PTH), and CAP, CIP were evaluated with Scantibodies Laboratory Inc test. In group I the densitometric examination was done using the Lunar DPX-L system, performing the overall bone measurement. In children from group I the average values of iPTH concentration and both CIP and CAP components were significantly elevated (p<0.05) as compared to group II. CAP/CIP ratio in group I was <1; in healthy children >1. Average concentrations of Ca and 1.25(OH)2D in serum of group I were lowered, although without statistical significance in comparison with group II. CAP/CIP ratio does not differentiate the children with bone disturbances. Densitometric examination revealed osteopenic changes in 3 children and osteoporosis in 2 children. There were no statistically significant correlations between the examined parameters. 1. The CIP/CAP ratio does not differentiate the bone mineral density status and it is not associated with biochemical parameters of calcium-phosphate metabolism. 2. This indicates its poor diagnostic utility with reference to mineralization disturbances in children with chronic kidney disease.

Pharmacological activation of aldehyde dehydrogenase 2 promotes osteoblast differentiation via bone morphogenetic protein-2 and induces bone anabolic effect

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

Mittal, Monika; Pal, Subhashis; China, Shyamsundar

Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuatedmore » the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40 mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40 mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress. - Highlights: • Alda-1 induced osteoblast differentiation that involved upregulation of ALDH2 and BMP-2 • Alda-1 attenuated acetaldehyde-induced inhibition of osteoblast differentiation • Alda-1 enhanced bone regeneration at the fracture site and peak bone mass achievement • Alda-1 reversed trabecular osteopenia in OVX rats via an osteoanabolic mechanism.« less

Deterioration of Cortical Bone Microarchitecture: Critical Component of Renal Osteodystrophy Evaluation.

PubMed

Sharma, Ashish K; Toussaint, Nigel D; Masterson, Rosemary; Holt, Stephen G; Rajapakse, Chamith S; Ebeling, Peter R; Mohanty, Sindhu T; Baldock, Paul; Elder, Grahame J

2018-05-23

Cortical bone is a significant determinant of bone strength and its deterioration contributes to bone fragility. Thin cortices and increased cortical porosity have been noted in patients with chronic kidney disease (CKD), but the "Turnover Mineralization Volume" classification of renal osteodystrophy does not emphasize cortical bone as a key parameter. We aimed to assess trabecular and cortical bone microarchitecture by histomorphometry and micro-CT in patients with CKD G5 and 5D (dialysis). Transiliac bone biopsies were performed in 14 patients undergoing kidney transplantation (n = 12) and parathyroidectomy (n = 2). Structural parameters were analysed by histomorphometry and micro-CT including trabecular bone volume, thickness (TbTh), number (TbN) and separation and cortical thickness (CtTh) and porosity (CtPo). Indices of bone remodelling and mineralisation were obtained and relationships to bone biomarkers examined. Associations were determined by Spearman's or Pearson's rank correlation coefficients. By micro-CT, trabecular parameters were within normal ranges in most patients, but all patients showed very low CtTh (127 ± 44 µm) and high CtPo (60.3 ± 22.5%). CtPo was inversely related to TbN (r = -0.56; p = 0.03) by micro-CT and to TbTh (r = -0.60; p = 0.024) by histomorphometry and correlated to parathyroid hormone values (r = 0.62; p = 0.021). By histomorphometry, bone turnover was high in 50%, low in 21% and normal in 29%, while 36% showed abnormal patterns of mineralization. Significant positive associations were observed between osteoblast surface, osteoclast surface, mineralization surface and bone turnover markers. Deterioration of cortical -microarchitecture despite predominantly normal trabecular parameters reinforces the importance of comprehensive cortical evaluation in patients with CKD. © 2018 S. Karger AG, Basel.

[Effect of 50 Hz 1.8 mT sinusoidal electromagnetic fields on bone mineral density in growing rats].

PubMed

Gao, Yu-Hai; Zhou, Yan-Feng; Li, Shao-Feng; Li, Wen-Yuan; Xi, Hui-Rong; Yang, Fang-Fang; Chen, Ke-Ming

2017-12-25

To study effects of 50 Hz 1.8 mT sinusoidal electromagnetic fields (SEMFs) on bone mineral density (BMD) in SD rats. Thirty SD rats weighted(110±10) and aged 1 month were randomly divided into control group and electromagnetic field group, 15 in each group. Normal control group of 50 Hz 0 mT density and sinusoidal electromagnetic field group of 50 Hz 1.8 mT were performed respectively with 1.5 h/d and weighted weight once a week, and observed food-intake. Rats were anesthesia by intraperitoneal injection and dual energy X-ray absorptiometry were used to detect bone density of whole body, and detected bone density of femur and vertebral body. Osteocalcin and tartrate-resistant acid phosphatase 5b were detected by ELSA; weighted liver, kidney and uterus to calculate purtenance index, then detected pathologic results by HE. Compared with control group, there was no significant change in weight every week, food-intake every day; no obvious change of bone density of whole body at 2 and 4 weeks, however bone density of whole body, bone density of excised femur and vertebra were increased at 6 weeks. Expression of OC was increased, and TRACP 5b expression was decreased. No change of HE has been observed in liver, kidney and uterus and organic index. 50 Hz 1.8 mT sinusoidal electromagnetic fields could improve bone formation to decrease relevant factors of bone absorbs, to improve peak bone density of young rats, in further provide a basis for clinical research electromagnetic fields preventing osteoporosis foundation.

Parathyroid hormone-dependent signaling pathways regulating genes in bone cells

NASA Technical Reports Server (NTRS)

Swarthout, John T.; D'Alonzo, Richard C.; Selvamurugan, Nagarajan; Partridge, Nicola C.

2002-01-01

Parathyroid hormone (PTH) is an 84-amino-acid polypeptide hormone functioning as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. PTH and PTH-related protein (PTHrP) indirectly activate osteoclasts resulting in increased bone resorption. During this process, PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone resorption. In addition to these catabolic effects, PTH has been demonstrated to be an anabolic factor in skeletal tissue and in vitro. As a result, PTH has potential medical application to the treatment of osteoporosis, since intermittent administration of PTH stimulates bone formation. Activation of osteoblasts by PTH results in expression of genes important for the degradation of the extracellular matrix, production of growth factors, and stimulation and recruitment of osteoclasts. The ability of PTH to drive changes in gene expression is dependent upon activation of transcription factors such as the activator protein-1 family, RUNX2, and cAMP response element binding protein (CREB). Much of the regulation of these processes by PTH is protein kinase A (PKA)-dependent. However, while PKA is linked to many of the changes in gene expression directed by PTH, PKA activation has been shown to inhibit mitogen-activated protein kinase (MAPK) and proliferation of osteoblasts. It is now known that stimulation of MAPK and proliferation by PTH at low concentrations is protein kinase C (PKC)-dependent in both osteoblastic and kidney cells. Furthermore, PTH has been demonstrated to regulate components of the cell cycle. However, whether this regulation requires PKC and/or extracellular signal-regulated kinases or whether PTH is able to stimulate other components of the cell cycle is unknown. It is possible that stimulation of this signaling pathway by PTH mediates a unique pattern of gene expression resulting in proliferation in osteoblastic and kidney cells; however, specific examples of this are still unknown. This review will focus on what is known about PTH-mediated cell signaling, and discuss the established or putative PTH-regulated pattern of gene expression in osteoblastic cells following treatment with catabolic (high) or anabolic (low) concentrations of the hormone.

Parathyroid hyperplasia

MedlinePlus

Enlarged parathyroid glands; Osteoporosis - parathyroid hyperplasia; Bone thinning - parathyroid hyperplasia; Osteopenia - parathyroid hyperplasia; High calcium level - parathyroid hyperplasia; Chronic kidney disease - parathyroid hyperplasia; ...

Bisphosphonates in chronic kidney disease; balancing potential benefits and adverse effects on bone and soft tissue.

PubMed

Toussaint, Nigel D; Elder, Grahame J; Kerr, Peter G

2009-01-01

Cardiovascular disease is highly prevalent in chronic kidney disease (CKD) and is often associated with increased vascular stiffness and calcification. Recent studies have suggested a complex interaction between vascular calcification and abnormalities of bone and mineral metabolism, with an inverse relationship between arterial calcification and bone mineral density (BMD). Although osteoporosis is recognized and treated in CKD 1 to 3, the interpretation of BMD levels in the osteoporotic range is controversial in CKD 4, 5, and 5D when renal osteodystrophy is generally present. In addition, there is a paucity of data for patients with CKD mineral and bone disorder (MBD), because studies using bisphosphonates in postmenopausal and glucocorticoid-induced osteoporosis have generally excluded patients with significant CKD. For these patients, treatment of low BMD using standard therapies for osteoporosis is not without potential for harm due to the possibility of worsening low bone turnover, osteomalacia, mixed uraemic osteodystrophy, and of exacerbated hyperparathyroidism; and bisphosphonates should only be used selectively and with caution. Some experimental and clinical studies have also suggested that bisphosphonates may reduce progression of extra-osseous calcification and inhibit the development of atherosclerosis. The authors review the potential benefits and risks associated with bisphosphonate use for bone protection in CKD, and assess their effect on vascular calcification and atherosclerosis.

Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity.

PubMed

Garske-Román, Ulrike; Sandström, Mattias; Fröss Baron, Katarzyna; Lundin, Lars; Hellman, Per; Welin, Staffan; Johansson, Silvia; Khan, Tanweera; Lundqvist, Hans; Eriksson, Barbro; Sundin, Anders; Granberg, Dan

2018-06-01

Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome. The study group comprised 200 consecutive patients with metastasized somatostatin receptor-positive neuroendocrine tumours progressing on standard therapy or not suitable for other therapeutic options. A treatment cycle consisted of 7.4 GBq 177 Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3-20% in 121 (60.5%) and >20% in 16 (8%). In 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22-30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39-53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity. Dosimetry-based therapy with 177 Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.

Peculiar Expression of CD3-Epsilon in Kidney of Ginbuna Crucian Carp.

PubMed

Miyazawa, Ryuichiro; Murata, Norifumi; Matsuura, Yuta; Shibasaki, Yasuhiro; Yabu, Takeshi; Nakanishi, Teruyuki

2018-01-01

TCR/CD3 complex is composed of the disulfide-linked TCR-αβ heterodimer that recognizes the antigen as a peptide presented by the MHC, and non-covalently paired CD3γε- and δε-chains together with disulfide-linked ζ-chain homodimers. The CD3 chains play key roles in T cell development and T cell activation. In the present study, we found nor or extremely lower expression of CD3ε in head- and trunk-kidney lymphocytes by flow cytometric analysis, while CD3ε was expressed at the normal level in lymphocytes from thymus, spleen, intestine, gill, and peripheral blood. Furthermore, CD4-1 + and CD8α + T cells from kidney express Zap-70, but not CD3ε, while the T cells from other tissues express both Zap-70 and CD3ε, although expression of CD3ε was low. Quantitative analysis of mRNA expression revealed that the expression level of T cell-related genes including tcrb, cd3 ε, zap-70 , and lck in CD4-1 + and CD8α + T cells was not different between kidney and spleen. Western blot analysis showed that CD3ε band was detected in the cell lysates of spleen but not kidney. To be interested, CD3ε-positive cells greatly increased after 24 h in in vitro culture of kidney leukocytes. Furthermore, expression of CD3ε in both transferred kidney and spleen leukocytes was not detected or very low in kidney, while both leukocytes expressed CD3ε at normal level in spleen when kidney and spleen leukocytes were injected into the isogeneic recipient. Lower expression of CD3ε was also found in kidney T lymphocytes of goldfish and carp. These results indicate that kidney lymphocytes express no or lower level of CD3ε protein in the kidney, although the mRNA of the gene was expressed. Here, we discuss this phenomenon from the point of function of kidney as reservoir for T lymphocytes in teleost, which lacks lymph node and bone marrow.

Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers.

PubMed

Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

2016-11-01

The presence of 137 Cesium ( 137 Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137 Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l -1 ) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (-11%) levels, but only for the rats exposed to 137 Cs intake in adulthood. Large changes in 17β-estradiol (-69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Expression of Dentin Sialophosphoprotein in Non-mineralized Tissues

PubMed Central

Prasad, Monica; Zhu, Qinglin; Sun, Yao; Wang, Xiaofang; Kulkarni, Ashok; Boskey, Adele; Feng, Jian Q.

2011-01-01

Dentin sialophosphoprotein (DSPP) and its cleaved products, dentin phosphoprotein (DPP) and dentin sialoprotein (DSP), play important roles in biomineralization. Believed to be tooth specific, the authors’ group revealed its expression in bone, and more recently, they and other groups also showed its expression in a few types of soft tissues. In this study, the authors systematically examined the expression of DSPP in a variety of non-mineralized tissues using reverse-transcription polymerase chain reaction (RT-PCR), real-time PCR, Western immunoblotting, and immunohistochemistry analyses in wild-type mice as well as β-galactosidase assays in the Dspp lacZ knock-in mice. These approaches showed the presence of DSPP in the salivary glands, cartilage, liver, kidney, and brain and its absence in the heart and spleen. Real-time PCR showed that the expression levels of DSPP mRNA in salivary glands, cartilage, liver, and kidney were higher than in the bone. Interestingly, DSPP was observed in the pericytes of blood vessels in the dental pulp, which are believed to be able to differentiate into odontoblasts. On the basis of these observations, the authors conclude that DSPP and/or its cleaved products may fulfill important functions in certain non-mineralized tissues in addition to its role in biomineralization. PMID:22043023

Herb Medicines against Osteoporosis: Active Compounds & Relevant Biological Mechanisms.

PubMed

Wu, Lei; Ling, Zhuoyan; Feng, Xueqin; Mao, Caiping; Xu, Zhice

2017-01-01

Osteoporosis is one of common bone disorders, affecting millions of people worldwide. Treatments of osteoporosis consist of pharmacotherapy and non-pharmacological interventions, such as mineral supplementation, lifestyle changes, and exercise programs. Due to the minimum side effects and favorable cost-effective therapeutic effects, herbal medicine has been widely applied in clinical practices for more than 2,000 years in China. Of the many traditional formulas reported for treating bone diseases, 4 single herbs namely (1) Herba Epimedii, (2) Rhizoma Drynariae, (3) Fructus Psoraleae, and (4) Cortex Eucommiae, are considered as the featured "Kidney-Yang" tonics, and frequently and effectively applied for preventing and treating osteoporosis. With the accruing development of modern chemistry, hundreds of active compounds have been identified and isolated for their anti-osteoporotic effects. This review would first sketch the phytochemistry of these featured "Kidney- Yang" tonics and present the pharmacological characteristics of the most abundant and bioactive compounds derived from the herb Herba Epimedii and Rhizoma Drynariae, including icariin and naringin. Then, the cellular and molecular underpinnings under anti-osteoporotic effects of icariin and naringin are discussed. The concerned structure-function relationships of the featured active herbal compounds would also be reviewed so as to pave the way for future drug design in treating osteoporosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Progress in the development of animal models of acute kidney injury and its impact on drug discovery.

PubMed

Sanz, Ana B; Sanchez-Niño, María Dolores; Martín-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrián M

2013-07-01

Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches. The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery. New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.

Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

PubMed Central

Kalaska, Bartlomiej; Pawlak, Krystyna; Domaniewski, Tomasz; Oksztulska-Kolanek, Ewa; Znorko, Beata; Roszczenko, Alicja; Rogalska, Joanna; Brzoska, Malgorzata M.; Lipowicz, Pawel; Doroszko, Michal; Pryczynicz, Anna; Pawlak, Dariusz

2017-01-01

The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD) represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx)-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR) as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone structure via AhR pathway. This finding opens new opportunities for the treatment/prevention of osteoporosis in CKD. PMID:29163188

Enhanced homing permeability and retention of bone marrow stromal cells (BMSC) by non-invasive pulsed focused ultrasound

PubMed Central

Ziadloo, Ali; Burks, Scott R.; Gold, Eric M.; Lewis, Bobbi K.; Chaudhry, Aneeka; Merino, Maria J.; Frenkel, Victor; Frank, Joseph A.

2012-01-01

Bone marrow stromal cells (BMSC) have shown significant promise in the treatment of disease, but their therapeutic efficacy is often limited by inefficient homing of systemically-administered cells, which results in low numbers of cells accumulating at sites of pathology. BMSC home to areas of inflammation where local expression of integrins and chemokine gradients are present. We demonstrated that non-destructive pulsed focused ultrasound (pFUS) exposures that emphasize the mechanical effects of ultrasound-tissue interactions induced local and transient elevations of chemoattractants (i.e., cytokines, integrins, and growth factors) in the murine kidney. pFUS-induced upregulation of cytokines occurred through approximately 1 day post-treatment and returned to contralateral kidney levels by day 3. This window of significant increases in cytokine expression was accompanied by local increases of other trophic factors and integrins that have been shown to promote BMSC homing. When BMSC were administered intravenously following pFUS treatment to a single kidney, enhanced homing, permeability, and retention of BMSC was observed in the treated kidney versus the contralateral kidney. Histological analysis revealed up to 8 times more BMSC in the peritubular regions of the treated kidneys on days 1 and 3 post-treatment. Furthermore, cytokine levels in pFUS-treated kidneys following BMSC administration were found to be similar to controls, suggesting modulation of cytokine levels by BMSC. pFUS could potentially improve cell-based therapies as a noninvasive modality to target BMSC homing by establishing local chemoattractant gradients and increasing expression of integrins to enhance tropism of BMSC toward treated tissues. PMID:22593018

Effects on vitamin D, bone and the kidney of switching from fixed-dose tenofovir disoproxil fumarate/emtricitabine/efavirenz to darunavir/ritonavir monotherapy: a randomized, controlled trial (MIDAS).

PubMed

Hamzah, Lisa; Tiraboschi, Juan M; Iveson, Helen; Toby, Martina; Mant, Christine; Cason, John; Burling, Keith; Wandolo, Emily; Jendrulek, Isabelle; Taylor, Chris; Ibrahim, Fowzia; Kulasegaram, Ranjababu; Teague, Alastair; Post, Frank A; Fox, Julie

2016-01-01

Efavirenz (EFV) has been associated with reductions in vitamin D (25[OH]D) and tenofovir (TDF) with increased bone turnover, reductions in bone mineral density (BMD) and renal tubular dysfunction. We hypothesized that switching from fixed-dose TDF/emtricitabine (FTC)/EFV to darunavir/ritonavir monotherapy (DRV/r) might increase 25(OH)D and BMD, and improve renal tubular function. Subjects with HIV RNA <50 copies/ml on TDF/FTC/EFV for ≥6 months were randomized 1:1 to ongoing TDF/FTC/EFV or DRV/r (800/100 mg once daily) for 48 weeks. The primary end point was change from baseline in 25(OH)D at week 48. Secondary end points included changes in BMD, bone turnover markers and renal tubular function. A total of 64 subjects (86% male, 66% white, mean [sd] CD4(+) T-cell count 537.3 [191.5]/mm(3)) were analysed. After adjustment for baseline 25(OH)D and demographics, at week 48 DRV/r monotherapy was associated with a +3.6 (95% CI 0.6, 6.6) ng/ml increase in 25(OH)D compared to TDF/FTC/EFV (P=0.02). DRV/r monotherapy was associated with an increase in BMD (+2.9% versus -0.003% at the neck of femur and +2.6% versus +0.008% at the lumbar spine for DRV/r versus TDF/FTC/EFV; P<0.05 for all) and reductions in bone biomarkers compared with those remaining on TDF/FTC/EFV. No significant difference in renal tubular function was observed. Reasons for discontinuation in the DRV/r arm included side effects (n=4) and viral load rebound (n=3), all of which resolved with DRV/r discontinuation or regimen intensification. Switching from TDF/FTC/EFV to DRV/r in patients with suppressed HIV RNA resulted in significant improvements in 25(OH)D and bone biomarkers, and a 2-3% increase in BMD.

Pharmacokinetic Models for the Elimination of Drinking Water Contaminants from the Body,

DTIC Science & Technology

1990-03-01

that are sequestered in the bones (lead, barium), in certain soft tissues such as the kidney ( cadmium ), and in the adipose tissue (DDT...slow" component (sequestered in 3 bone or in adipose tissue ). Finally, much more attention must be given to differences among I individuals and among...lead from bone, effectively reducing the half-life. Fasting or starvation can mobilize toxicants 3 stored in adipose tissue . Competition for enzyme

Age dependent regulation of bone-mass and renal function by the MEPE ASARM-motif

PubMed Central

Zelenchuk, Lesya V; Hedge, Anne-Marie; Rowe, Peter S N

2015-01-01

Context Mice with null mutations in Matrix Extracellular Phosphoglycoprotein (MEPE) have increased bone mass, increased trabecular density and abnormal cancellous bone (MN-mice). These defects worsen with age and MEPE over expression induces opposite effects. Also, Genome Wide Association studies show MEPE plays a major role in bone mass. We hypothesized the conserved C-terminal MEPE ASARM-motif is chiefly responsible for regulating bone mass and trabecular structure. Design To test our theory we over expressed C-terminal ASARM-peptide in MN-mice using the Col1α1 promoter (MNAt-mice). We then compared the bone and renal phenotypes of the MNAt-mouse with the MN-mouse and the X-linked hypophosphatemic rickets mouse (HYP). The HYP mouse over expresses ASARM-peptides and is defective for the PHEX gene. Results The MN-mouse developed increased bone mass, bone strength and trabecular abnormalities that worsened markedly with age. Defects in bone formation were chiefly responsible with suppressed sclerostin and increased active β-catenin. Increased uric acid levels also suggested abnormalities in purine-metabolism and a reduced fractional excretion of uric acid signaled additional renal transport changes. The MN mouse developed a worsening hyperphosphatemia and reduced FGF23 with age. An increase in the fractional excretion of phosphate (FEP) despite the hyperphosphatemia confirms an imbalance in kidney-intestinal phosphate regulation. Also, the MN mice showed an increased creatinine clearance suggesting hyperfiltration. A reversal of the MN bone-renal phenotype changes occurred with the MNAt mice including the apparent hyperfiltration. The MNAt mice also developed localized hypomineralization, hypophosphatemia and increased FGF23. Conclusions The C-terminal ASARM-motif plays a major role in regulating bone–mass and cancellous structure as mice age. In healthy mice, the processing and release of free ASARM-peptide is chiefly responsible for preserving normal bone and renal function. Free ASARM-peptide also effects renal mineral phosphate handling by influencing FGF23 expression. These findings have implications for understanding age-dependent osteoporosis, unraveling drug-targets and developing treatments. PMID:26051469

Bone scan findings in hypervitaminosis D: case report. [/sup 99m/Tc tracer technique

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

Fogelman, I.; McKillop, J.H.; Cowden, E.A.

1977-12-01

Bone scans in three patients showed generalized symmetrical increased uptake of radiopharmaceutical by the skeleton and absent or faint kidney images. It is thought that these appearances may be attributable to excess vitamin D, and other possible contributing factors, including the presence of renal osteodystrophy, are discussed.

The enigma of aluminum deposition in bone tissue from a patient with chronic kidney disease: a case report.

PubMed

Meira, Rodrigo Dias de; Carbonara, Cinthia Esbrile Moraes; Quadros, Kélcia Rosana da Silva; Santos, Carolina Urbini Dos; Schincariol, Patrícia; Pêssoa, Gustavo de Souza; Arruda, Marco Aurélio Zezzi; Jorgetti, Vanda; Oliveira, Rodrigo Bueno de

2018-06-04

About four decades ago, the relationship between dialysis-dementia and aluminum (Al) began to be established. The restriction of drugs containing Al and improvements on water quality used for dialysis resulted in the clinical disappearance of Al intoxication. However, high prevalence of Al deposition in bone tissue from Brazilian dialysis patients is still being detected. Through the case report of a patient on hemodialysis (HD) for one year, presenting significant Al deposition in bone tissue, we speculated if this problem is not being underestimated. We used extensive investigation to identify potential sources of Al exposure with a careful review of medication history and water quality controls. Al concentration was measured by different methods, including mass spectrometry, in poly-electrolyte concentrate solutions and solution for peritoneal dialysis, in an attempt to elucidate the possible sources of contamination. The objective of this case report is to alert the medical community about a potential high prevalence of Al deposition in bone tissue and to discuss the possible sources of contamination in patients with chronic kidney disease (CKD).

Fibroblast Growth Factor 23 in Long-Duration Spaceflight

NASA Technical Reports Server (NTRS)

Bokhari, R.; Zwart, S. R.; Fields, E.; Heer, M.; Sibonga, J.; Smith, S. M.

2015-01-01

Many nutritional factors influence bone, from the basics of calcium and vitamin D, to factors which influence bone through acid/base balance, including protein, sodium, and more. Fibroblast growth factor 23 (FGF23) is a recently identified factor, secreted from osteocytes, which is involved in classic (albeit complex) feedback loops controlling phosphorus homeostasis through both vitamin D and parathyroid hormone (PTH) (1, 2). As osteocytes are gravity sensing cells, it is important to determine if there are changes in FGF23 during spaceflight. In extreme cases, such as chronic kidney disease, FGF23 levels are highly elevated. FGF23 imbalances, secondary to dietary influences, may contribute to skeletal demineralization and kidney stone risk during spaceflight.

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism.

PubMed

Kakareko, Katarzyna; Rydzewska-Rosolowska, Alicja; Brzosko, Szymon; Gozdzikiewicz-Lapinska, Joanna; Koc-Zorawska, Ewa; Samocik, Pawel; Kozlowski, Robert; Mysliwiec, Michal; Naumnik, Beata; Hryszko, Tomasz

2017-04-01

Increased concentration of fibroblast growth factor 23 (FGF-23) and decreased levels of soluble Klotho (sKL) are linked to negative clinical outcomes among patients with chronic kidney disease and acute kidney injury. Therefore, it is reasonable to hypothesize that GFR reduction caused by nephrectomy might alter mineral metabolism and induces adverse consequences. Whether nephrectomy due to urological indications causes derangements in FGF-23 and sKL has not been studied. The aim of the study was to evaluate the effect of acute GFR decline due to unilateral nephrectomy on bone metabolism, FGF-23 and sKL levels. This is a prospective, single-centre observational study of patients undergoing nephrectomy due to urological indications. Levels of C-terminal FGF-23 (c-FGF-23), sKL and bone turnover markers [β-crosslaps (CTX), bone-specific alkaline phosphatase (bALP) and tartrate-resistant acid phosphatase 5b (TRAP 5b)] were measured before and after surgery (5 ± 2 days). Twenty-nine patients were studied (14 females, age 63.0 ± 11.6, eGFR 87.3 ± 19.2 ml/min/1.73 m 2 ). After surgery, eGFR significantly declined (p < 0.0001). Nephrectomy significantly decreased sKL level [709.8 (599.9-831.2) vs. 583.0 (411.7-752.6) pg/ml, p < 0.001] and did not change c-FGF-23 concentration [70.5 (49.8-103.3) vs. 77.1 (60.5-109.1) RU/ml, p = 0.9]. Simultaneously, alterations in bone turnover markers were observed. Serum concentration of CTX increased [0.49 (0.4-0.64) vs. 0.59 (0.46-0.85) ng/ml, p = 0.001], while bALP and TRAP 5b decreased [23.6 (18.8-31.4) vs. 17.9 (15.0-22.0) U/l, p < 0.0001 and 3.3 (3.0-3.7) vs. 2.8 (2.3-3.2) U/l, p < 0.001, respectively]. Nephrectomy among patients with preserved renal function before surgery does not increase c-FGF-23 but reduces sKL. Moreover, nephrectomy results in derangements in bone turnover markers in short-term follow-up. These changes may participate in pathogenesis of bone disease after nephrectomy.

Inflammation and linear bone growth: the inhibitory role of SOCS2 on GH/IGF-1 signaling.

PubMed

Farquharson, Colin; Ahmed, S Faisal

2013-04-01

Linear bone growth is widely recognized to be adversely affected in children with chronic kidney disease (CKD) and other chronic inflammatory disorders. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is anabolic to the skeleton and inflammatory cytokines compromise bone growth through a number of different mechanisms, which include interference with the systemic as well as the tissue-level GH/IGF-1 axis. Despite attempts to promote growth and control disease, there are an increasing number of reports of the persistence of poor growth in a substantial proportion of patients receiving rhGH and/or drugs that block cytokine action. Thus, there is an urgent need to consider better and alternative forms of therapy that are directed specifically at the mechanism of the insult which leads to abnormal bone health. Suppressor of cytokine signaling 2 (SOCS2) expression is increased in inflammatory conditions including CKD, and is a recognized inhibitor of GH signaling. Therefore, in this review, we will focus on the premise that SOCS2 signaling represents a critical pathway in growth plate chondrocytes through which pro-inflammatory cytokines alter both GH/IGF-1 signaling and cellular function.

Estrogenic Activity Including Bone Enhancement and Effect on Lipid Profile of Luteolin-7-O-glucoside Isolated from Trifolium alexandrinum L. in Ovariectomized Rats.

PubMed

Ammar, N M; El-Hawary, S S; Mohamed, D A; El-Halawany, A M; El-Anssary, A A; El-Kassem, L T Abou; Hussein, R A; Jaleel, G A Abdel; El-Dosoky, A H

2016-05-01

Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Bone Density, Microarchitecture, and Tissue Quality Long-term After Kidney Transplant.

PubMed

Pérez-Sáez, María José; Herrera, Sabina; Prieto-Alhambra, Daniel; Nogués, Xavier; Vera, María; Redondo-Pachón, Dolores; Mir, Marisa; Güerri, Roberto; Crespo, Marta; Díez-Pérez, Adolfo; Pascual, Julio

2017-06-01

Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry is used to assess bone health in kidney transplant recipients (KTR). Trabecular bone score and in vivo microindentation are novel techniques that directly measure trabecular microarchitecture and mechanical properties of bone at a tissue level and independently predict fracture risk. We tested the bone status of long-term KTR using all 3 techniques. Cross-sectional study including 40 KTR with more than 10 years of follow-up and 94 healthy nontransplanted subjects as controls. Bone mineral density was measured at lumbar spine and the hip. Trabecular bone score was measured by specific software on the dual-energy x-ray absorptiometry scans of lumbar spine in 39 KTR and 77 controls. Microindentation was performed at the anterior tibial face with a reference-point indenter device. Bone measurements were standardized as percentage of a reference value, expressed as bone material strength index (BMSi) units. Multivariable (age, sex, and body mass index-adjusted) linear regression models were fitted to study the association between KTR and BMD/BMSi/trabecular bone score. Bone mineral density was lower at lumbar spine (0.925 ± 0.15 vs 0.982 ± 0.14; P = 0.025), total hip (0.792 ± 0.14 vs 0.902 ± 0.13; P < 0.001), and femoral neck (0.667 ± 0.13 vs 0.775 ± 0.12; P < 0.001) in KTR than in controls. BMSi was also lower in KTR (79.1 ± 7.7 vs 82.9 ± 7.8; P = 0.012) although this difference disappeared after adjusted model (P = 0.145). Trabecular bone score was borderline lower (1.21 ± 0.14 vs 1.3 ± 0.15; adjusted P = 0.072) in KTR. Despite persistent decrease in BMD, trabecular microarchitecture and tissue quality remain normal in long-term KTR, suggesting important recovery of bone health.

Changes in bone mineral metabolism parameters, including FGF23, after discontinuing cinacalcet at kidney transplantation.

PubMed

Barros, Xoana; Fuster, David; Paschoalin, Raphael; Oppenheimer, Federico; Rubello, Domenico; Perlaza, Pilar; Pons, Francesca; Torregrosa, Jose V

2015-05-01

Little is known about the effects of the administration of cinacalcet in dialytic patients who are scheduled for kidney transplantation, and in particular about the changes in FGF23 and other mineral metabolism parameters after surgery compared with recipients not on cinacalcet at kidney transplantation. We performed a prospective observational cohort study with recruitment of consecutive kidney transplant recipients at our institution. Patients were classified according to whether they were under treatment with cinacalcet before transplantation. Bone mineral metabolism parameters, including C-terminal FGF23, were measured at baseline, on day 15, and at 1, 3, and 6 months after transplantation. In previously cinacalcet-treated patients, cinacalcet therapy was discontinued on the day of surgery and was not restarted after transplantation. A total of 48 kidney transplant recipients, 20 on cinacalcet at surgery and 28 cinacalcet non-treated patients, completed the follow-up. Serum phosphate declined significantly in the first 15 days after transplantation with no differences between the two groups, whereas cinacalcet-treated patients showed higher FGF23 levels, although not significant. After transplantation, PTH and serum calcium were significantly higher in cinacalcet-treated patients. We conclude that patients receiving cinacalcet on dialysis presented similar serum phosphate levels but higher PTH and serum calcium levels during the initial six months after kidney transplantation than cinacalcet non-treated patients. The group previously treated with cinacalcet before transplantation showed higher FGF23 levels without significant differences, so further studies should investigate its relevance in the management of these patients.

The Calcium-Sensing Receptor in Health and Disease.

PubMed

Díaz-Soto, G; Rocher, A; García-Rodríguez, C; Núñez, L; Villalobos, C

2016-01-01

The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca 2+ and by other physiological cations including Mg 2+ , amino acids, and polyamines. CaSR is the most important master controller of the extracellular Ca 2+ homeostatic system being expressed at high levels in the parathyroid gland, kidney, gut and bone, where it regulates parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca 2+ absorption and resorption, respectively. Gain and loss of function mutations in the CaSR are responsible for severe disturbances in extracellular Ca 2+ metabolism. CaSR agonists (calcimimetics) and antagonists (calcilytics) are in use or under intense research for treatment of hyperparathyroidism secondary to kidney failure and hypocalcemia with hypercalciuria, respectively. Expression of the CaSR extends to other tissues and systems beyond the extracellular Ca 2+ homeostatic system including the cardiovascular system, the airways, and the nervous system where it may play physiological functions yet to be fully understood. As a consequence, CaSR has been recently involved in different pathologies including uncontrolled blood pressure, vascular calcification, asthma, and Alzheimer's disease. Finally, the CaSR has been shown to play a critical role in cancer either contributing to bone metastasis and/or acting as a tumor suppressor in some forms of cancer (parathyroid cancer, colon cancer, and neuroblastoma) and as oncogene in others (breast and prostate cancers). Here we review the role of CaSR in health and disease in calciotropic tissues and others beyond the extracellular calcium homeostatic system. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum fibroblastic growth factor 23 in acute Sarcoidosis and normal kidney function.

PubMed

Sexton, Donal J; O'Reilly, M W; Geoghegan, P; Kinsella, S M; Moran, P J; O'Regan, A W

2016-08-01

Serum fibroblastic growth factor (FGF) 23 has recently been established as a major physiological regulator of phosphate homeostasis and may have a causal role in adverse cardiovascular and bone outcomes. However its role in states of disordered phosphate homeostasis and normal kidney function is as yet under characterised. To investigate whether this biomarker of vascular calcification and adverse bone outcomes is detectable in patients with sarcoidosis. We conducted a cross sectional study on a convenience sample of patients presenting with acute sarcoidosis to a respiratory tertiary referral unit. We set out to systematically examine the characteristics and determinants of serum FGF-23 in patients presenting with acute sarcoidosis. We studied 39 patients, 26 were male. Mean (SD) age was 33 (9.6) years. 15.4% of patients had a serum level of FGF-23 ≥ 9.9 pg/mL. The remaining 84.6% of patients had a serum FGF-23 < 9.9 pg/mL. Those with a detectable serum FGF-23 had a significantly higher serum calcium (P = 0.007), and lower serum iPTH (P<0.001). Serum phosphate and 25-hydroxyvitamin D were not statistically significantly different between groups (P=0.25 and P=0.83). The proportion of patients with stage II disease on CXR was higher in those with a detectable FGF-23 (P<0.001). Serum FGF-23 was below the level of detection in the majority of this cohort of patients presenting with acute sarcoidosis. A detectable serum FGF-23 was associated with a higher serum calcium and lower serum iPTH.

Preliminary clinical trial in percutaneous nephrolithotomy using a real-time navigation system for percutaneous kidney access

NASA Astrophysics Data System (ADS)

Rodrigues, Pedro L.; Moreira, António H. J.; Rodrigues, Nuno F.; Pinho, A. C. M.; Fonseca, Jaime C.; Lima, Estevão.; Vilaça, João. L.

2014-03-01

Background: Precise needle puncture of renal calyces is a challenging and essential step for successful percutaneous nephrolithotomy. This work tests and evaluates, through a clinical trial, a real-time navigation system to plan and guide percutaneous kidney puncture. Methods: A novel system, entitled i3DPuncture, was developed to aid surgeons in establishing the desired puncture site and the best virtual puncture trajectory, by gathering and processing data from a tracked needle with optical passive markers. In order to navigate and superimpose the needle to a preoperative volume, the patient, 3D image data and tracker system were previously registered intraoperatively using seven points that were strategically chosen based on rigid bone structures and nearby kidney area. In addition, relevant anatomical structures for surgical navigation were automatically segmented using a multi-organ segmentation algorithm that clusters volumes based on statistical properties and minimum description length criterion. For each cluster, a rendering transfer function enhanced the visualization of different organs and surrounding tissues. Results: One puncture attempt was sufficient to achieve a successful kidney puncture. The puncture took 265 seconds, and 32 seconds were necessary to plan the puncture trajectory. The virtual puncture path was followed correctively until the needle tip reached the desired kidney calyceal. Conclusions: This new solution provided spatial information regarding the needle inside the body and the possibility to visualize surrounding organs. It may offer a promising and innovative solution for percutaneous punctures.

Lead in the tissues of terrestrial raptors in southern Ontario, Canada, 1995-2001.

PubMed

Martin, Pamela A; Campbell, Douglas; Hughes, Kimberley; McDaniel, Tana

2008-02-25

Terrestrial raptors which feed on upland hunted game species may increase their risk to lead exposure and lead poisoning by ingesting lead shot found in the tissues of prey. Lead exposure in 225 individuals of nineteen species of terrestrial raptors, collected as carcasses in southern Ontario from 1995-2001, was examined through the analysis of bone, liver and kidney tissues. In this study, one red-tailed hawk contained liver lead concentrations and exhibited signs consistent with lead poisoning. Liver and kidney concentrations of one turkey vulture were also significantly higher than that associated with subclinical effects. This same bird, plus another turkey vulture and a northern harrier, had elevated bone lead concentrations (>10 microg/g dw) associated with possible toxicity. Turkey vultures had the highest mean concentrations of lead in bone and kidney compared to other raptor species. While it appeared only a single bird suffered acute lead poisoning, lead levels exceeded threshold concentrations associated with subclinical or acute toxicity in 4 of 225, almost 2%, of terrestrial raptors assessed. Given the association between lead exposure in raptors and hunting of game species reported in other studies, the continued use of lead shot for upland hunting in Ontario likely remains as one of the primary sources of lead and a continued risk to these birds of prey.

Bone marrow chimerism as a strategy to produce tolerance in solid organ allotransplantation.

PubMed

Hu, Min; Alexander, Stephen I; Yi, Shounan

2016-12-01

Clinical transplant tolerance has been most successfully achieved combining hematopoietic chimerism with kidney transplantation. This review outlines this strategy in animal models and human transplantation, and possible clinical challenges. Kidney transplant tolerance has been achieved through chimerism in several centers beginning with Massachusetts General Hospital's success with mixed chimerism in human leukocyte antigen (HLA)-mismatched patients and the Stanford group with HLA-matched patients, and the more recent success of the Northwestern protocol achieving full chimerism. This has challenged the original view that stable mixed chimerism is necessary for organ graft tolerance. However, among the HLA-mismatched kidney transplant-tolerant patients, loss of mixed chimerism does not lead to renal-graft rejection, and the development of host Foxp3+ regulatory T cells has been observed. Recent animal models suggest that graft tolerance through bone marrow chimerism occurs through both clonal deletion and regulatory immune cells. Further, Tregs have been shown to improve chimerism in animal models. Animal studies continue to suggest ways to improve our current clinical strategies. Advances in chimerism protocols suggest that tolerance may be clinically achievable with relative safety for HLA-mismatched kidney transplants.

Mechanism Underlying Linezolid-induced Thrombocytopenia in a Chronic Kidney Failure Mouse Model

PubMed Central

Nishijo, Nao; Tsuji, Yasuhiro; Matsunaga, Kazuhisa; Kutsukake, Masahiko; Okazaki, Fumiyasu; Fukumori, Shiro; Kasai, Hidefumi; Hiraki, Yoichi; Sakamaki, Ippei; Yamamoto, Yoshihiro; Karube, Yoshiharu; To, Hideto

2017-01-01

Objective: To investigate the relationship between renal function and linezolid (LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq) was administrated intravenously to LZD-administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD-administered CRD group than in the LZD-nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD-administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD-induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression. PMID:28405130

Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption.

PubMed

Wongdee, Kannikar; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2017-01-01

Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D 3 , and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.

Relationship between plasma fibroblast growth factor-23 concentration and bone mineralization in children with renal failure on peritoneal dialysis.

PubMed

Wesseling-Perry, Katherine; Pereira, Renata C; Wang, Hejing; Elashoff, Robert M; Sahney, Shobha; Gales, Barbara; Jüppner, Harald; Salusky, Isidro B

2009-02-01

Fibroblast growth factor (FGF)-23 is produced in bone, and circulating levels are markedly elevated in patients with end-stage kidney disease, but the relationship between plasma levels of FGF-23 and bone histology in dialysis patients with secondary hyperparathyroidism is unknown. The aim of the study was to evaluate the correlation between plasma levels of FGF-23 and bone histology in pediatric patients with end-stage kidney disease who display biochemical evidence of secondary hyperparathyroidism. We performed a cross-sectional analysis of the relationship between plasma FGF-23 levels and bone histomorphometry. The study was conducted in a referral center. Participants consisted of forty-nine pediatric patients who were treated with maintenance peritoneal dialysis and who had serum PTH levels (1st generation Nichols assay) greater than 400 pg/ml. There were no interventions. Plasma FGF-23 levels and bone histomorphometry were measured. No correlation existed between values of PTH and FGF-23. Bone formation rates correlated with PTH (r = 0.44; P < 0.01), but not with FGF-23. Higher FGF-23 concentrations were associated with decreased osteoid thickness (r = -0.49; P < 0.01) and shorter osteoid maturation time (r = -0.48; P < 0.01). High levels of FGF-23 are associated with improved indices of skeletal mineralization in dialyzed pediatric patients with high turnover renal osteodystrophy. Together with other biomarkers, FGF-23 measurements may indicate skeletal mineralization status in this patient population.

Detection and characterization of naturally acquired West Nile virus infection in a female wild turkey.

PubMed

Zhang, Z; Wilson, F; Read, R; Pace, L; Zhang, S

2006-03-01

An adult female wild turkey exhibiting disorientation and failure to flee when approached was submitted to the Mississippi Veterinary Research and Diagnostic Laboratory. Gross pathologic examination revealed evidence of dehydration and the presence of modest numbers of adult nematodes in the small intestine. Histologic examination revealed extensive multifocal perivascular lymphocytic infiltration in brain, marked heterophilic hyperplasia in bone marrow, and multifocal interstitial lymphocytic infiltration in heart, pancreas, ventriculus, and skeletal muscles. West Nile virus (WNV) was isolated from the brain, lung, and kidney tissues using cultured Vero cells. Higher copies of viral RNA were detected from brain, lung, and kidney than from heart, liver, or spleen by quantitative real-time reverse transcription-polymerase chain reaction (RRT-PCR) analysis. Immunohistochemical (IHC) analysis detected WNV antigen in various tissues including neurons, kidney, respiratory tract epithelium, heart, and bone marrow. On the basis of the data from this investigation, it is concluded that WNV caused encephalitis along with many other pathologic changes in the affected wild turkey.

Trace elements distribution in hawksbill turtle (Eretmochelys imbricata) and green turtle (Chelonia mydas) tissues on the northern coast of Bahia, Brazil.

PubMed

de Macêdo, Gustavo R; Tarantino, Taiana B; Barbosa, Isa S; Pires, Thaís T; Rostan, Gonzalo; Goldberg, Daphne W; Pinto, Luis Fernando B; Korn, Maria Graças A; Franke, Carlos Roberto

2015-05-15

Concentrations of elements (As, Al, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Mo, Na, Ni, Pb, Sb, Se, Sr, V, Zn) were determined in liver, kidneys and bones of Eretmochelys imbricata and Chelonia mydas specimens found stranded along the northern coast of Bahia, Brazil. Results showed that the concentrations of Cd, Cu, Ni and Zn in the liver and kidneys of juvenile C. mydas were the highest found in Brazil. We also observed a significant difference (p<0.05) on the bioaccumulation of trace elements between the two species: Al, Co, Mo, Na and Se in the liver; Al, Cr, Cu, K, Mo, Ni, Pb, Sr and V in the kidneys; and Al, Ba, Ca, Cd, Mn, Ni, Pb, Se, Sr and V in the bones. This study represents the first report on the distribution and concentration of trace elements in E. imbricata in the Brazilian coast. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mixed Donor Chimerism Following Simultaneous Pancreas-Kidney Transplant.

PubMed

Rashidi, Armin; Brennan, Daniel C; Amarillo, Ina E; Wellen, Jason R; Cashen, Amanda

2018-06-01

Graft-versus-host disease after solid-organ transplant is exceedingly rare. Although the precise pathogenetic mechanisms are unknown, a progressive increase in donor chimerism is a requirement for its development. The incidence of mixed donor chimerism and its timeline after simultaneous pancreas-kidney transplant is unknown. After encountering 2 cases of graft-versus-host disease after simultaneous pancreas-kidney transplant at our institution over a period of < 2 years, a collaborative pilot study was conducted by the bone marrow transplant, nephrology, and abdominal transplant surgery teams. We enrolled all consecutive patients undergoing sex-mismatched simultaneous pancreas-kidney transplant over 1 year and longitudinally monitored donor chimerism using fluorescence in situ hybridization for sex chromosomes. We found no evidence for chimerism in our 7 patients. In a comprehensive literature review, we found a total of 25 previously reported cases of graft-versus-host disease after kidney, pancreas, and simultaneous pancreas-kidney transplants. The median onset of graft-versus-host disease was approximately 5 weeks after transplant, with a median of about 2 weeks of delay between first presentation and diagnosis. Skin, gut, and bone marrow were almost equally affected at initial presentation, and fever of unknown origin occurred in more than half of patients. The median survival measured from the first manifestation of graft-versus-host disease was only 48 days. Within the limitations related to small sample size, our results argue against an unusually high risk of graft-versus-host disease after simultaneous pancreas-kidney transplant. Collaboration between solid-organ and stem cell transplant investigators can be fruitful and can improve our understanding of the complications that are shared between the 2 fields.

X-linked hypophosphataemia: a homologous disorder in humans and mice.

PubMed

Tenenhouse, H S

1999-02-01

X-linked hypophosphatemia is an inherited disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets and osteomalacia, hypophosphataemia, and aberrant renal Pi reabsorption and vitamin D metabolism. Studies in murine Hyp and Gy homologues have identified a specific defect in Na+-Pi cotransport at the brush border membrane, abnormal regulation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) synthesis and degradation, and an intrinsic defect in bone mineralization. The mutant gene has been identified in XLH patients, by positional cloning, and in Hyp and Gy mice, and was designated PHEX/Phex to signify a PHosphate-regulating gene with homology to Endopeptidases on the X chromosome. PHEX/Phex is expressed in bones and teeth but not in kidney and efforts are under way to elucidate how loss of PHEX/Phex function elicits the mutant phenotype. Based on its homology to endopeptidases, it is postulated that PHEX/Phex is involved in the activation or inactivation of a peptide hormone(s) which plays a key role in the regulation of bone mineralization, renal Pi handling and vitamin D metabolism.

Biological monitoring of heavy metal contaminations using owls.

PubMed

Kim, Jungsoo; Oh, Jong-Min

2012-03-01

Iron, manganese, copper, lead and cadmium were measured in the livers, muscles, kidneys and bones of Eurasian Eagle Owls (Bubo bubo), Brown Hawk Owls (Nixos scutulata) and Collared Scops Owls (Otus lempiji) from Korea. Iron concentrations by tissue within species did not differ, but there were significant differences among tissues across all species. Manganese and copper concentrations in muscles, kidneys and bones, but not livers, differed among species and also differed among tissues in the three owl species. We suggest that manganese and copper concentrations from this study were far below the level associated with their toxicity. Lead concentrations significantly differed among all species for livers and bones, and among tissues for each species. Cadmium concentrations were significantly different among species for all tissues and among tissues in Eurasian Eagle Owls and Collared Scops Owls. For most samples, lead concentrations in livers and bones, and cadmium in livers and kidneys, were within the background levels for wild birds. For some Eurasian Eagle Owls and Collared Scops Owls, lead concentrations were at an acute exposure level, whilst lead concentrations were at a chronic exposure level in Brown Hawk Owls. Cadmium concentrations were at a chronic exposure level in all three owl species. Acute and chronic poisoning was significantly correlated between indicator tissues. We suggest that lead and cadmium contamination in Eurasian Eagle Owls may reflect a Korean source, Brown Hawk Owls may reflect Korean and wintering sites, and Collared Scops Owls may reflect breeding and/or wintering sites. This journal is © The Royal Society of Chemistry 2012

[Comparative study of X-ray digital DTS imaging and kidney ureter bladder radiography in urinary calculi].

PubMed

Liu, Shifeng; Guo, Jian; Hu, Xiaokun; Zhang, Hao; Shang, Qingjun; Xu, Wenjian; Feng, Weihua

2015-07-07

To investigate the value of X-ray digital tomosynthesis (DTS) in the diagnosis of urinary stones compared with kidney ureter bladder radiography. Between February 2011 and February 2012, 80 consecutively enrolled patients with urinary stones proved by UMDCT, the total number of which was 138, underwent additional DTS and KUB (kidney, ureter and bladder) then the number of stones and the proportions (the sensitivity of detecting stones) were recorded under all kinds of circumstances. Any two cases were selected in comparison with each other among the following four cases (DTS and KUB before and after bowel preparation).The data from all cases were statistically processed by chi-square test of four-fold table. The diagnostic sensitivity of DTS before and after bowel preparation, KUB before and after preparation were 94.2%, 96.4%, 47.8% and 66.7%, respectively. No significant differences between DTS before bowel preparation and DTS after bowel preparation were found. Significant differences were observed in other five ways. DTS is hardly affected by intestinal gas, feces and bones compared with KUB. Use of DTS results in improved detection rate and definition of stones with the same positioning function as KUB.

Dose-response analysis of heavy metal toxicants in man. Direct in vivo assessment of body burden

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

Ellis, K.J.

Differences in uptake, metabolism, and excretion of heavy metals makes selection of a suitable biological media as a monitor of body burden very difficult. Exposure assessments based on body fluid levels can provide, at best, only general population estimates. The most frequently monitored media are blood, urine, nail or hair clippings, sweat, and saliva. Unfortunately each of these tissues can be influenced by recent exposure conditions and are not accurate indices of the total dose or body burden. However, direct in vivo measurements of body burden in humans, have recently been performed. This nuclear technique has focused on the measurementsmore » of kidney and liver cadmium (Cd) by neutron activation analysis and bone lead (Pb) determinations using x-ray fluorescence. The dose-response relationship for renal dysfunction based on the direct in vivo body burden for Cd is presented. The most probable Cd value for the kidney associated with renal impairment is approximately 35 mg. Approximately 10% of the subjects with 20 mg Cd in the kidney will have moderately elevated ..beta../sub 2/-microglobulin, an early indicator of potential renal functional changes. 11 refs., 5 figs., 2 tabs.« less

Fate of Neutrophils during the Recovery Phase of Ischemia/Reperfusion Induced Acute Kidney Injury

PubMed Central

2017-01-01

Effective clearance of inflammatory cells is required for resolution of inflammation. Here, we show in vivo evidence that apoptosis and reverse transendothelial migration (rTEM) are important mechanisms in eliminating neutrophils and facilitating recovery following ischemia/reperfusion injury (IRI) of the kidney. The clearance of neutrophils was delayed in the Bax knockout (KO)BM → wild-type (WT) chimera in which bone marrow derived cells are partially resistant to apoptosis, compared to WTBM → WT mice. These mice also showed delayed functional, histological recovery, increased tissue cytokines, and accelerated fibrosis. The circulating intercellular adhesion molecule-1 (ICAM-1)+ Gr-1+ neutrophils displaying rTEM phenotype increased during the recovery phase and blockade of junctional adhesion molecule-C (JAM-C), a negative regulator of rTEM, resulted in an increase in circulating ICAM-1+ neutrophils, faster resolution of inflammation and recovery. The presence of Tamm-Horsfall protein (THP) in circulating ICAM-1+ neutrophils could suggest that they are derived from injured kidneys. In conclusion, we suggest that apoptosis and rTEM are critically involved in the clearance mechanisms of neutrophils during the recovery phase of IRI. PMID:28875605

Endocrine Abnormalities in Patients with Chronic Kidney Disease.

PubMed

Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej

2015-01-01

In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases.

The new insight on the regulatory role of the vitamin D3 in metabolic pathways characteristic for cancerogenesis and neurodegenerative diseases.

PubMed

Kubis, Adriana Maria; Piwowar, Agnieszka

2015-11-01

Apart from the classical function of regulating intestinal, bone and kidney calcium and phosphorus absorption as well as bone mineralization, there is growing evidence for the neuroprotective function of vitamin D3 through neuronal calcium regulation, the antioxidative pathway, immunomodulation and detoxification. Vitamin D3 and its derivates influence directly or indirectly almost all metabolic processes such as proliferation, differentiation, apoptosis, inflammatory processes and mutagenesis. Such multifactorial effects of vitamin D3 can be a profitable source of new therapeutic solutions for two radically divergent diseases, cancer and neurodegeneration. Interestingly, an unusual association seems to exist between the occurrence of these two pathological states, called "inverse comorbidity". Patients with cognitive dysfunctions or dementia have considerably lower risk of cancer, whereas survivors of cancer have lower prevalence of central nervous system (CNS) disorders. To our knowledge, there are few publications analyzing the role of vitamin D3 in biological pathways existing in carcinogenic and neuropathological disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

A hybrid 3D region growing and 4D curvature analysis-based automatic abdominal blood vessel segmentation through contrast enhanced CT

NASA Astrophysics Data System (ADS)

Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Shimada, Mitsuo; Iinuma, Gen

2017-03-01

In abdominal disease diagnosis and various abdominal surgeries planning, segmentation of abdominal blood vessel (ABVs) is a very imperative task. Automatic segmentation enables fast and accurate processing of ABVs. We proposed a fully automatic approach for segmenting ABVs through contrast enhanced CT images by a hybrid of 3D region growing and 4D curvature analysis. The proposed method comprises three stages. First, candidates of bone, kidneys, ABVs and heart are segmented by an auto-adapted threshold. Second, bone is auto-segmented and classified into spine, ribs and pelvis. Third, ABVs are automatically segmented in two sub-steps: (1) kidneys and abdominal part of the heart are segmented, (2) ABVs are segmented by a hybrid approach that integrates a 3D region growing and 4D curvature analysis. Results are compared with two conventional methods. Results show that the proposed method is very promising in segmenting and classifying bone, segmenting whole ABVs and may have potential utility in clinical use.

Multiple myeloma: Diagnosis and management issues in patients with pre-existing chronic kidney disease.

PubMed

Vadlamudi, Srilatha; Annapareddy, Siva Nagendra Reddy

2016-01-01

Multiple myeloma is one of the most common malignancies encountered in clinical practice. Renal involvement in myeloma is a well-recognized entity. Although rare, another special situation that a nephrologist can encounter is myeloma occurring in a patient with preexisting chronic kidney disease (CKD) due to other etiologies. Anemia, bone pains and hypercalcemia, which commonly indicate the diagnosis of myeloma in the general population, are not useful in the presence of CKD. The sensitivity and specificity of serum free light chain assay is decreased in the presence of renal failure. Chemotherapy-related adverse effects are high compared with that in patients without CKD; this is attributed to the decreased clearance of drugs and the additive effect of chemotherapy-related adverse effects to the complications of CKD. Autologous and allogenic bone marrow transplantation can be attempted in this group of patients with non-myeloablative-conditioning regimens. Combined bone marrow and renal transplantation remains a viable option in this group of patients to increase life expectancy and quality of life.

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones.

PubMed

Vezzoli, Giuseppe; Macrina, Lorenza; Rubinacci, Alessandro; Spotti, Donatella; Arcidiacono, Teresa

2016-08-08

Idiopathic hypercalciuria is a frequent defect in calcium kidney stone formers that is associated with high intestinal calcium absorption and osteopenia. Characteristics distinguishing hypercalciuric stone formers from hypercalciuric patients without kidney stone history (HNSFs) are unknown and were explored in our study. We compared 172 hypercalciuric stone formers with 36 HNSFs retrospectively selected from patients referred to outpatient clinics of the San Raffaele Hospital in Milan from 1998 to 2003. Calcium metabolism and lumbar bone mineral density were analyzed in these patients. A strontium oral load test was performed: strontium was measured in 240-minute urine and serum 30, 60, and 240 minutes after strontium ingestion; serum strontium concentration-time curve and renal strontium clearance were evaluated to estimate absorption and excretion of divalent cations. Serum strontium concentration-time curve (P<0.001) and strontium clearance (4.9±1.3 versus 3.5±2.7 ml/min; P<0.001) were higher in hypercalciuric stone formers than HNSFs, respectively. The serum strontium-time curve was also higher in hypercalciuric stone formers with low bone mineral density (n=42) than in hypercalciuric stone formers with normal bone mineral density (n=130; P=0.03) and HNSFs with low (n=22; P=0.01) or normal bone mineral density (n=14; P=0.02). Strontium clearance was greater in hypercalciuric stone formers with normal bone mineral density (5.3±3.4 ml/min) than in hypercalciuric stone formers and HNSFs with low bone mineral density (3.6±2.5 and 3.1±2.5 ml/min, respectively; P=0.03). Multivariate regression analyses displayed that strontium absorption at 30 minutes was positively associated calcium excretion (P=0.03) and negatively associated with lumbar bone mineral density z score (P=0.001) in hypercalciuric stone formers; furthermore, hypercalciuric patients in the highest quartile of strontium absorption had increased stone production risk (odds ratio, 5.06; 95% confidence interval, 1.2 to 20.9; P=0.03). High calcium absorption in duodenum and jejunum may expose hypercalciuric patients to the risk of stones because of increased postprandial calcium concentrations in urine and tubular fluid. High calcium absorption may identify patients at risk of bone loss among stone formers. Copyright © 2016 by the American Society of Nephrology.

Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like symptoms in zebrafish.

PubMed

Botthof, Jan Gregor; Bielczyk-Maczyńska, Ewa; Ferreira, Lauren; Cvejic, Ana

2017-05-30

RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size. We show that some of these symptoms stem from both decreased proliferation and increased apoptosis of embryonic hematopoietic stem and progenitor cells. Comutation of p53 was able to rescue the hematopoietic defects seen in the single mutants, but led to tumor development. We further demonstrate that prolonged inflammatory stress can exacerbate the hematological impairment, leading to an additional decrease in kidney marrow cell numbers. These findings strengthen the assignment of RAD51 as a Fanconi gene and provide more evidence for the notion that aberrant p53 signaling during embryogenesis leads to the hematological defects seen later in life in FA. Further research on this zebrafish FA model will lead to a deeper understanding of the molecular basis of bone marrow failure in FA and the cellular role of RAD51.

TGF-β/BMP proteins as therapeutic targets in renal fibrosis. Where have we arrived after 25 years of trials and tribulations?

PubMed

Muñoz-Félix, José M; González-Núñez, María; Martínez-Salgado, Carlos; López-Novoa, José M

2015-12-01

The understanding of renal fibrosis in chronic kidney disease (CKD) remains as a challenge. More than 10% of the population of developed countries suffer from CKD. Proliferation and activation of myofibroblasts and accumulation of extracellular matrix proteins are the main features of kidney fibrosis, a process in which a large number of cytokines are involved. Targeting cytokines responsible for kidney fibrosis development might be an important strategy to face the problem of CKD. The increasing knowledge of the signaling pathway network of the transforming growth factor beta (TGF-β) superfamily members, such as the profibrotic cytokine TGF-β1 or the bone morphogenetic proteins (BMPs), and their involvement in the regulation of kidney fibrosis, has stimulated numerous research teams to look for potential strategies to inhibit profibrotic cytokines or to enhance the anti-fibrotic actions of other cytokines. The consequence of all these studies is a better understanding of all these canonical (Smad-mediated) and non-canonical signaling pathways. In addition, the different receptors involved for signaling of each cytokine, the different combinations of type I-type II receptors, and the presence and function of co-receptors that can influence the biological response have been also described. However, are these studies leading to suitable strategies to block the appearance and progression of kidney fibrosis? In this review, we offer a critical perspective analyzing the achievements using the most important strategies developed up till now: TGF-β antibodies, chemical inhibitors of TGF-β receptors, miRNAs and signaling pathways and BMP agonists with a potential role as therapeutic molecules against kidney fibrosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

PubMed Central

Mason, Roger M

2013-01-01

Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Vitamin D and gene networks in human osteoblasts

PubMed Central

van de Peppel, Jeroen; van Leeuwen, Johannes P. T. M.

2014-01-01

Bone formation is indirectly influenced by 1,25-dihydroxyvitamin D3 (1,25D3) through the stimulation of calcium uptake in the intestine and re-absorption in the kidneys. Direct effects on osteoblasts and bone formation have also been established. The vitamin D receptor (VDR) is expressed in osteoblasts and 1,25D3 modifies gene expression of various osteoblast differentiation and mineralization-related genes, such as alkaline phosphatase (ALPL), osteocalcin (BGLAP), and osteopontin (SPP1). 1,25D3 is known to stimulate mineralization of human osteoblasts in vitro, and recently it was shown that 1,25D3 induces mineralization via effects in the period preceding mineralization during the pre-mineralization period. For a full understanding of the action of 1,25D3 in osteoblasts it is important to get an integrated network view of the 1,25D3-regulated genes during osteoblast differentiation and mineralization. The current data will be presented and discussed alluding to future studies to fully delineate the 1,25D3 action in osteoblast. Describing and understanding the vitamin D regulatory networks and identifying the dominant players in these networks may help develop novel (personalized) vitamin D-based treatments. The following topics will be discussed in this overview: (1) Bone metabolism and osteoblasts, (2) Vitamin D, bone metabolism and osteoblast function, (3) Vitamin D induced transcriptional networks in the context of osteoblast differentiation and bone formation. PMID:24782782

Febuxostat Prevents Renal Interstitial Fibrosis by the Activation of BMP-7 Signaling and Inhibition of USAG-1 Expression in Rats.

PubMed

Cao, Jing; Li, Yong; Peng, Yingxian; Zhang, Yaqian; Li, Huanhuan; Li, Ran; Xia, Anzhou

2015-01-01

Renal interstitial fibrosis (RIF) is a common pathology associated with end-stage renal diseases. The activation of bone morphogenetic protein-7 (BMP-7)-Smad1/5/8 pathway seems to alleviate RIF. Uterine sensitization-associated gene-1 (USAG-1), a kidney-specific BMPs antagonist, is associated with the development and prognosis of several renal diseases. Febuxostat is a xanthine oxidase inhibitor that can attenuate the renal dysfunction of patients. The purpose of this study was to investigate the effects of febuxostat on renal fibrosis and to clarify the mechanisms underlying these effects. Rats were randomly divided into 6 groups termed a sham-operated group, a unilateral ureteral obstruction (UUO) group, 3 doses of febuxostat groups (low, intermediate and high doses) and a sham group treated with high-dose febuxostat. After 14 days, renal function, relative kidney weight, accumulation of glycogen and collagens were examined by different methods. Expression of α-SMA, transforming growth factor-β1 (TGF-β1), BMP-7 and USAG-1 was detected by western blotting and RT-PCR, respectively. The phosphorylation level of Smad1/5/8 was also quantified by western blotting. The renal function was declined, and large amounts of glycogen and collagens were deposited in the kidneys of UUO rats compared with the rats in the sham group. Besides, expression of α-SMA and USAG-1 in these kidneys was elevated, and the TGF-β1 was also activated, while the BMP-7-Smad1/5/8 pathway was inhibited. Febuxostat reversed the changes stated earlier, exhibiting protective effects on RIF induced by UUO. Febuxostat was able to attenuate RIF caused by UUO, which was associated with the activation of BMP-7-Smad1/5/8 pathway and the inhibition of USAG-1 expression in the kidneys of UUO rats. © 2015 S. Karger AG, Basel.

Nephrectomy (Kidney Removal)

MedlinePlus

... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

Klotho converts canonical FGF receptor into a specific receptor for FGF23.

PubMed

Urakawa, Itaru; Yamazaki, Yuji; Shimada, Takashi; Iijima, Kousuke; Hasegawa, Hisashi; Okawa, Katsuya; Fujita, Toshiro; Fukumoto, Seiji; Yamashita, Takeyoshi

2006-12-07

FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions, whereas most other family members are thought to regulate various cell functions at a local level. The renotropic activity of circulating FGF23 indicates the possible presence of an FGF23-specific receptor in the kidney. Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor. Using a renal homogenate, we found that Klotho binds to FGF23. Forced expression of Klotho enabled the high-affinity binding of FGF23 to the cell surface and restored the ability of a renal cell line to respond to FGF23 treatment. Moreover, FGF23 incompetence was induced by injecting wild-type mice with an anti-Klotho monoclonal antibody. Thus, Klotho is essential for endogenous FGF23 function. Because Klotho alone seemed to be incapable of intracellular signalling, we searched for other components of the FGF23 receptor and found FGFR1(IIIc), which was directly converted by Klotho into the FGF23 receptor. Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors.

Requirement for digestible calcium by eleven- to twenty-five-kilogram pigs as determined by growth performance, bone ash concentration, calcium and phosphorus balances, and expression of genes involved in transport of calcium in intestinal and kidney cells.

PubMed

González-Vega, J C; Liu, Y; McCann, J C; Walk, C L; Loor, J J; Stein, H H

2016-08-01

Two experiments were conducted to determine the requirement for standardized total tract digestible (STTD) Ca by 11- to 25-kg pigs based on growth performance, bone ash, or Ca and P retention and to determine the effect of dietary Ca on expression of genes related to Ca transport in the jejunum and kidneys. Six diets were formulated to contain 0.36% STTD P and 0.32, 0.40, 0.48, 0.56, 0.64, or 0.72% STTD Ca by including increasing quantities of calcium carbonate in the diets at the expense of cornstarch. Two additional diets contained 0.72% STTD Ca and 0.33% or 0.40% STTD P to determine if 0.36% STTD P had negative effects on the Ca requirement. The same batch of all diets was used in both experiments. In Exp. 1, 256 pigs (11.39 ± 1.21 kg initial BW) were randomly allotted to the 8 diets with 4 pigs per pen and 8 replicate pens per diet in a randomized complete block design. On the last day of the experiment, 1 pig from each pen was euthanized and the right femur and intestine and kidney samples were collected. Results indicated that ADG and G:F started to decline (linear and quadratic, < 0.05) at 0.54 and 0.50% STTD Ca, respectively. In contrast, bone ash increased (quadratic, < 0.05) as dietary Ca increased and reached a plateau indicating that the requirement for STTD Ca to maximize bone ash was 0.48%. Bone ash, but not ADG or G:F, increased (linear, < 0.01) as STTD increased in the diets. The mRNA expression of genes related to transcellular Ca transport decreased (linear, < 0.01) in the jejunum and in kidneys (linear and quadratic, < 0.01) as dietary Ca increased. In Exp. 2, 80 pigs (13.12 ± 1.79 kg initial BW) were placed in metabolism crates and randomly allotted to the 8 diets with 10 replicate pigs per diet in a randomized complete block design. Fecal and urine samples were collected using the marker-to-marker approach. Results indicated that the requirement for STTD Ca to maximize Ca and P retention (g/d) was 0.60 and 0.49%, respectively. In conclusion, the STTD Ca requirement by 11- to 25-kg pigs to maximize bone ash was 0.48%; however, ADG and G:F declined if more than 0.54 or 0.50% STTD Ca, respectively, was fed, and the minimum concentration of Ca needed to maximize ADG and G:F could not be determined under the conditions of this experiment. Increasing dietary Ca decreased the mRNA expression of several genes related to transcellular Ca transport in the jejunum and the kidneys.

Clinical and Virological Outcome of European Patients Infected With HIV

ClinicalTrials.gov

2018-04-26

HIV; Hepatitis B; Hepatitis C; AIDS; Coinfection; Cardiovascular Diseases; Diabetes Mellitus; Acidosis, Lactic; Renal Insufficiency; Fractures, Bone; End Stage Liver Disease; Kidney Failure, Chronic; Proteinuria

End-stage kidney disease

MedlinePlus

... Sleep problems Swelling of the feet and hands ( edema ) Vomiting , often in the morning ... legs syndrome Stroke , seizures , and dementia Swelling and edema Weakening of the bones and fractures related to ...

Tenofovir alafenamide (TAF) treatment of HBV, what are the unanswered questions?

PubMed

Viganò, Mauro; Loglio, Alessandro; Grossi, Glenda; Lampertico, Pietro

2018-02-01

Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir (TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients. However, reduced kidney function and loss of bone mineral density have been reported in some CHB patients treated with TDF. Consequent to these safety issues, tenofovir alafenamide (TAF) [Vemlidy®], a phosphonate prodrug of TFV, was developed for the treatment of CHB patients. Areas covered: The favourable pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day) thus reducing systemic exposure to tenofovir and improving the bone and renal safety, keeping however the same virological efficacy, compared to TDF 300 mg/day. In two ongoing 96-week phase III trials in mainly treatment-naive HBeAg-positive or -negative patients, TAF showed similar viral suppression but was associated with significantly higher alanine aminotransferase normalization rates and more favourable renal and bone safety compared to TDF. In a 48-week TAF switch study enrolling patients treated with TDF for 96 weeks, glomerular, tubular and bone safety parameters rapidly improved while virological suppression was maintained. Expert commentary: Waiting long-term large scale clinical practice studies aimed to confirm these advantages, TAF represents an helpful treatment option for both naïve and TDF-exposed CHB patients.

Persistent Low Level of Osterix Accelerates Interleukin-6 Production and Impairs Regeneration after Tissue Injury

PubMed Central

Baek, Wook-Young; Park, Seung-Yoon; Kim, Yeo Hyang; Lee, Min-A; Kwon, Tae-Hwan; Park, Kwon-Moo; de Crombrugghe, Benoit; Kim, Jung-Eun

2013-01-01

Osterix (Osx) is an essential transcription factor for osteoblast differentiation and bone formation. Osx knockout show a complete absence of bone formation, whereas Osx conditional knockout in osteoblasts produce an osteopenic phenotype after birth. Here, we questioned whether Osx has a potential role in regulating physiological homeostasis. In Osx heterozygotes expressing low levels of Osx in bones, the expression levels of pro-inflammatory cytokines were significantly elevated, indicating that reduced Osx expression may reflect an inflammatory-prone state. In particular, the expression of interleukin-6, a key mediator of chronic inflammation, was increased in Osx heterozygotes and decreased in Osx overexpressing osteoblasts, and transcriptionally down-regulated by Osx. Although no significant differences were revealed in renal morphology and function between Osx heterozygotes and wild-type under normoxic conditions, recovery of kidneys after ischemic damage was remarkably delayed in Osx heterozygotes, as indicated by elevated blood urea nitrogen and creatinine levels, and by morphological alterations consistent with acute tubular necrosis. Eventually, protracted low Osx expression level caused an inflammatory-prone state in the body, resulting in the enhanced susceptibility to renal injury and the delayed renal repair after ischemia/reperfusion. This study suggests that the maintenance of Osx expression in bone is important in terms of preventing the onset of an inflammatory-prone state. PMID:23922826

Outcome Measures Used to Report Kidney Function in Studies Investigating Surgical Management of Kidney Tumours: A Systematic Review.

PubMed

Ellis, Robert J; Cho, Yeoungjee; Del Vecchio, Sharon J; McStea, Megan; Morais, Christudas; Coombes, Jeff S; Wood, Simon T; Gobe, Glenda C; Francis, Ross S

2018-05-01

Most practice decisions relevant to preserving kidney function in patients managed surgically for kidney tumours are driven by observational studies. A wide range of outcome measures are used in these studies, which reduces comparability and increases the risk of reporting bias. To comprehensively and succinctly describe the outcomes used to evaluate kidney function in studies evaluating surgical management of kidney tumours. Electronic search of the PubMed database was conducted to identify studies with at least one measure of kidney function in patients managed surgically for kidney tumours, published between January 2000 and September 2017. Abstracts were initially screened for eligibility. Full texts of articles were then evaluated in more detail for inclusion. A narrative synthesis of the evidence was conducted. A total of 312 studies, involving 127905 participants, were included in this review. Most were retrospective (n=274) studies and conducted in a single centre (n=264). Overall, 78 unique outcome measures were identified, which were grouped into six outcome categories. Absolute postoperative kidney function (n=187), relative kidney function (n=181), and postoperative chronic kidney disease (n=131) were most frequently reported. Kidney function was predominantly quantified using estimated glomerular filtration rate or creatinine clearance (n=255), most using the modification of diet in renal disease equation (n=182). Only 70 studies provided rationale for specific outcome measures used. There is significant variability in the reporting and quantification of kidney function in studies evaluating patients managed surgically for kidney tumours. A standardised approach to measuring and reporting kidney function will increase the effectiveness of outcomes reported and improve relevance of research findings within a clinical context. Although we know that the removal of a kidney can reduce kidney function, clinical significance of various approaches is a matter of debate. This article demonstrates significant variability in the way kidney function was reported across all studies of patients with kidney cancer undergoing surgery, indicating a need for standardisation. Copyright © 2018 European Association of Urology. All rights reserved.

Systemic candidiasis and mesenteric mast cell tumor with multiple metastases in a dog.

PubMed

Matsuda, Kazuya; Sakaguchi, Kanako; Kobayashi, Shintaro; Tominaga, Makiko; Hirayama, Kazuko; Kadosawa, Tsuyoshi; Taniyama, Hiroyuki

2009-02-01

A 5-year-old female miniature dachshund presenting with persistent vomiting and diarrhea had two concurrent rare pathological conditions: systemic candidiasis and mesenteric mast cell tumor with multiorgan metastases. Neoplastic mast cells formed mass in the mesentery of the cecal-colonic region and were also found in the liver, spleen, kidneys, lungs, adrenal grands, ovaries, bone marrow and other tissues. The cells had intracytoplasmic granules with metachromasia and were immunohistochemically positive for c-kit and histamine. Granulomatous lesions with fungal organisms were present in the heart, lungs, kidneys, pancreas, subserosal and surrounding adipose tissue of the duodenum, thyroid glands and mesenteric mass, and phagocytosed organisms were detected in the liver and bone marrow. Bacteriologically and immunohistochemically, the fungi were consistent with Candida albicans.

The effects of low environmental cadmium exposure on bone density

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

Trzcinka-Ochocka, M., E-mail: ochocka@imp.lodz.pl; Jakubowski, M.; Szymczak, W.

2010-04-15

Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9;more » 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction ({beta}{sub 2}M-U RBP, NAG), glomerular dysfunction (Alb-U and {beta}{sub 2}M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone density.« less

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease.

PubMed

Molina, Pablo; Carrero, Juan J; Bover, Jordi; Chauveau, Philippe; Mazzaferro, Sandro; Torres, Pablo Ureña

2017-10-01

The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non-genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25-hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Magnesium and cardiovascular complications of chronic kidney disease.

PubMed

Massy, Ziad A; Drüeke, Tilman B

2015-07-01

Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Abundant experimental evidence suggests a physiological role of magnesium in cardiovascular function, and clinical evidence suggests a role of the cation in cardiovascular disease in the general population. The role of magnesium in CKD-mineral and bone disorder, and in particular its impact on cardiovascular morbidity and mortality in patients with CKD, is however not well understood. Experimental studies have shown that magnesium inhibits vascular calcification, both by direct effects on the vessel wall and by indirect, systemic effects. Moreover, an increasing number of epidemiologic studies in patients with CKD have shown associations of serum magnesium levels with intermediate and hard outcomes, including vascular calcification, cardiovascular events and mortality. Intervention trials in these patients conducted to date have had small sample sizes and have been limited to the study of surrogate parameters, such as arterial stiffness, vascular calcification and atherosclerosis. Randomized controlled trials are clearly needed to determine the effects of magnesium supplementation on hard outcomes in patients with CKD.

Xp11.2 translocation renal cell carcinoma with multiple bone metastases: A case report

PubMed Central

LIU, JIAJU; SU, ZHENGMING; LI, YIFAN; CHEN, DUQUN; NI, LIANGCHAO; MAO, XIANGMING; YANG, SHANGQI; LAI, YONGQING

2016-01-01

Xp11.2 translocation/transcription factor enhancer 3 (TFE3) fusion gene associated with renal cell carcinoma (Xp11.2 translocation RCC) is rare and occurs predominantly in children and adolescents. The current study reports the case of a 14-year-old male with Xp11.2 translocation RCC, who presented with chest pain that had persisted for 1 month. A solid neoplasm was located in the left kidney of the patient. Contrast-enhanced computed tomography revealed the presence of a solid mass in the kidney, with uneven enhancement. Destruction of multiple bones was also observed. The patient was treated with a radical nephrectomy. The pathological examination of the tumor revealed that the tumor cells contained an eosinophilic cytoplasm in the renal interstitial tissue. Immunohistochemistry revealed that the tumor cells expressed P504S, cluster of differentiation 10, pan-cytokeratin, vimentin and TFE3. In conclusion, Xp11.2 translocation RCC is a rare type of kidney cancer. Diagnosing this disease prior to surgery is challenging, and providing a definite diagnosis requires histopathological and immunohistochemical examination, while genetic analysis may also be required. PMID:26998154

Xp11.2 translocation renal cell carcinoma with multiple bone metastases: A case report.

PubMed

Liu, Jiaju; Su, Zhengming; Li, Yifan; Chen, Duqun; Ni, Liangchao; Mao, Xiangming; Yang, Shangqi; Lai, Yongqing

2016-03-01

Xp11.2 translocation/transcription factor enhancer 3 (TFE3) fusion gene associated with renal cell carcinoma (Xp11.2 translocation RCC) is rare and occurs predominantly in children and adolescents. The current study reports the case of a 14-year-old male with Xp11.2 translocation RCC, who presented with chest pain that had persisted for 1 month. A solid neoplasm was located in the left kidney of the patient. Contrast-enhanced computed tomography revealed the presence of a solid mass in the kidney, with uneven enhancement. Destruction of multiple bones was also observed. The patient was treated with a radical nephrectomy. The pathological examination of the tumor revealed that the tumor cells contained an eosinophilic cytoplasm in the renal interstitial tissue. Immunohistochemistry revealed that the tumor cells expressed P504S, cluster of differentiation 10, pan-cytokeratin, vimentin and TFE3. In conclusion, Xp11.2 translocation RCC is a rare type of kidney cancer. Diagnosing this disease prior to surgery is challenging, and providing a definite diagnosis requires histopathological and immunohistochemical examination, while genetic analysis may also be required.

[Mineral and bone disorders in renal transplantation].

PubMed

Bacchetta, Justine; Lafage-Proust, Marie-Hélène; Chapurlat, Roland

2013-12-01

The deregulation of bone and mineral metabolism during chronic kidney disease (CKD) is a daily challenge for physicians, its management aiming at decreasing the risk of both fractures and vascular calcifications. Renal transplantation in the context of CKD, with pre-existing renal osteodystrophy as well as nutritional impairment, chronic inflammation, hypogonadism and corticosteroids exposure, represents a major risk factor for bone impairment in the post-transplant period. The aim of this review is therefore to provide an update on the pathophysiology of mineral and bone disorders after renal transplantation. Copyright © 2013 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Protein electrophoresis - serum

MedlinePlus

... digestive tract to absorb proteins ( protein-losing enteropathy ) Malnutrition Kidney disorder called nephrotic syndrome Scarring of the ... may indicate: Abnormally low level of LDL cholesterol Malnutrition Increased gamma globulin proteins may indicate: Bone marrow ...

Evaluation of a vaccination regimen and care in relation to follow-up and treatment of patients with inflammatory bowel disease.

PubMed

Yamamoto-Furusho, J K; Sarmiento-Aguilar, A; Parra-Holguín, N N; Bozada-Gutiérrez, K E

2018-03-28

During the clinical course of inflammatory bowel disease, different causes can compromise kidney, liver, and bone marrow function and increase the risk for osteoporosis, infections, and neoplasias. The aim of the present study was to describe the follow-up of Mexican patients with inflammatory bowel disease in relation to their vaccination regimen, treatment-associated risks, and cancer screening. A retrospective cross-sectional study was conducted within the time frame of February and June 2017. One hundred patients that had a histopathologic diagnosis of inflammatory bowel disease were surveyed about their follow-up vaccination regimen, treatment-associated risks, and cancer screening. SPSS v24 software was employed for the statistical analysis. One hundred patients with inflammatory bowel disease were studied (90% with ulcerative colitis and 10% with Crohn's disease; 60% women, 40% men): 75% stated that they had no vaccination regimen. A total of 71.4% of the women had at least one Pap smear in their lives and 28.6% did not have them done annually. Twenty-four percent of the patients wore sun block daily. A total of 18.2% of the patients with more than a 10-year progression of ulcerative colitis had an annual colonoscopy. Yearly kidney function was registered in 57.1% of the patients, 92.9% had a yearly complete blood count, and 78.6% had yearly liver function tests. A total of 34.8% of patients had no bone densitometry in their case records. These results are a red flag suggesting the need to reinforce the role of the primary healthcare providers in relation to vaccination follow-up and the need to improve the education of the patient in relation to inflammatory bowel disease. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Perianal streptococcal cellulitis

MedlinePlus

... usually occurs in children, often during or after strep throat , nasopharyngitis, or streptococcal skin infection ( impetigo ). Children ... fistula , or abscess Bleeding, discharge Bloodstream or other streptococcal infections (including heart, joint, and bone) Kidney disease (acute ...

Calcium isotope signature: new proxy for net change in bone volume for chronic kidney disease and diabetic rats.

PubMed

Tanaka, Yu-Ki; Yajima, Nobuyuki; Higuchi, Yusuke; Yamato, Hideyuki; Hirata, Takafumi

2017-12-01

Herein, we measure the Ca isotope ratios ( 44 Ca/ 42 Ca and 43 Ca/ 42 Ca) in serum and bone samples collected from rats with chronic kidney disease (CKD) or diabetes mellitus (DM). For the serum samples, the isotope ratios are lower for the CKD (δ 44 Ca/ 42 Ca serum = 0.16 ± 0.11‰; 2SD, n = 6) and the DM (δ 44 Ca/ 42 Ca serum = -0.11 ± 0.25‰; 2SD, n = 7) rats than that for the control rats (δ 44 Ca/ 42 Ca serum = 0.25 ± 0.04‰; 2SD, n = 7). Bone samples from two distinct positions of 20 rats in total, namely, the center and proximal parts of the tibial diaphysis, are subject to Ca isotope analysis. The resulting δ 44 Ca/ 42 Ca values for the bone of the proximal part are about 0.3‰ lower than that for the serum samples from the same rats. The larger isotope fractionations between the serum and bone are consistent with previously reported data for vertebrate animals (e.g., Skulan and DePaolo, 1999), which suggests the preferential incorporation of lighter Ca isotopes through bone formation. For the bones from the control and CKD rats, there were no differences in the δ 44 Ca/ 42 Ca values between the positions of the bone. In contrast, the δ 44 Ca/ 42 Ca values of the bone for the DM rats were different between the positions of the bone. Due to the lower bone turnover rate for the DM rats, the δ 44 Ca/ 42 Ca for the middle of the diaphysis can reflect the Ca isotopes in the bone formed prior to the progression of DM states. Thus, the resulting δ 44 Ca/ 42 Ca values show a clear correlation with bone mineral density (BMD). This can be due to the release of isotopically lighter Ca from the bone to the serum. In the present study, our data demonstrate that the δ 44 Ca/ 42 Ca value for serum can be used as a new biomarker for evaluating changes in bone turnover rate, followed by changes in bone volume.

Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery.

PubMed

Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N

2009-10-01

The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.

Opportunities for improving management of advanced chronic kidney disease.

PubMed

Patwardhan, Meenal B; Matchar, David B; Samsa, Gregory P; Haley, William E

2008-01-01

Evidence suggests that management of advanced chronic kidney disease affects patient outcomes. To identify clinical areas that demand attention from a quality improvement perspective, we sought to examine the extent of conformance to an advanced chronic kidney disease guideline in a range of practices. A total of 237 patient medical records were abstracted from 4 primary care providers and 4 nephrology private practices across the country. In the practices studied, management of advanced chronic kidney disease patients was suboptimal for patients managed by primary care providers as well as those managed by nephrologists (overall conformance 27% and 42%, respectively), specifically for anemia, bone disease, and timing for renal replacement therapy. The current exercise (in conjunction with a literature search and focused and individual interviews with providers and patients) offered valuable information that was used to develop a toolkit for optimizing management of advanced chronic kidney disease.

Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer

ClinicalTrials.gov

2013-06-20

Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Head and Neck Cancer; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Retinoblastoma; Sarcoma; Testicular Germ Cell Tumor

FGF23 Neutralizing Antibody Ameliorates Hypophosphatemia and Impaired FGF Receptor Signaling in Kidneys of HMWFGF2 Transgenic Mice.

PubMed

Du, E; Xiao, L; Hurley, M M

2017-03-01

High molecular weight FGF2 transgenic mice (HMWTg) phenocopy the Hyp mouse, homolog of human X-linked hypophosphatemic rickets with phosphate wasting and abnormal fibroblast growth factor (FGF23), fibroblast growth factor receptor (FGFR), Klotho and mitogen activated protein kinases (MAPK) signaling in kidney. In this study, we assessed whether short-term (24 h) in vivo administration of FGF23 neutralizing antibody (FGF23Ab) could rescue hypophosphatemia and impaired FGFR signaling in kidneys of HMWTg male mice. Bone mineral density and bone mineral content in 1-month-old HMWTg mice were significantly reduced compared with Control/VectorTg mice. Serum FGF23 was significantly increased in HMWTg compared with VectorTg. Serum phosphate was significantly reduced in HMWTg and was rescued by FGF23Ab. Serum parathyroid hormone (PTH) was significantly increased in HMWTg but was not reduced by FGF23Ab. 1, 25(OH) 2 D was inappropriately normal in serum of HMWTg and was significantly increased in both Vector and HMWTg by FGF23Ab. Analysis of HMWTg kidneys revealed significantly increased mRNA expression of the FGF23 co-receptor Klotho, transcription factor mRNAs for early growth response-1 transcription factor (Egr-1), and c-fos were all significantly decreased by FGF23Ab. A significant reduction in the phosphate transporter Npt2a mRNA was also observed in HMWTg kidneys, which was increased by FGF23Ab. FGF23Ab reduced p-FGFR1, p-FGFR3, KLOTHO, p-ERK1/2, C-FOS, and increased NPT2A protein in HMWTg kidneys. We conclude that FGF23 blockade rescued hypophosphatemia by regulating FGF23/FGFR downstream signaling in HMWTg kidneys. Furthermore, HMWFGF2 isoforms regulate PTH expression independent of FGF23/FGFR signaling. J. Cell. Physiol. 232: 610-616, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The biodistribution and dosimetry of {sup 117m}Sn DTPA with special emphasis on active marrow absorbed doses

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

Stubbs, J.; Atkins, H.

1999-01-01

{sup 117m}Sn(4+) DTPA is a new radiopharmaceutical for the palliation of pain associated with metastatic bone cancer. Recently, the Phase 2 clinical trials involving 47 patients were completed. These patients received administered activities in the range 6.7--10.6 MBq/kg of body mass. Frequent collections of urine were acquired over the first several hours postadministration and daily cumulative collections were obtained for the next 4--10 days. Anterior/posterior gamma camera images were obtained frequently over the initial 10 days. Radiation dose estimates were calculated for 8 of these patients. Each patient`s biodistribution data were mathematically simulated using a multicompartmental model. The model consistedmore » of the following compartments: central, bone, kidney, other tissues, and cumulative urine. The measured cumulative urine data were used as references for the cumulative urine excretion compartment. The total-body compartment (sum of the bone surfaces, central, kidney, and other tissues compartments) was reference to all activity not excreted in the urine.« less

Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

PubMed Central

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

2014-01-01

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

Melorheostosis and somatic mosaicism

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

Fryns, J.P.

1995-08-28

Melorheostosis is a rare congenital disorder of the bone and mesenchymal tissue. The longitudinal, cortical hyperostosis in the long bones has the appearance of wax flowing down the side of a candle. The short bones appear to manifest endosteal bone deposition. Usually only one limb is affected, but bilateral involvement is possible. Also, the skull, vertebrae, pelvis, and ribs can be affected. In 1980 we reported on a 3-year-old girl with clinical and radiological findings of melorheostosis, with manifest involvement of the left lower limb and scleroderma of the overlying soft tissues. Subsequently, at age 17 years, she was admittedmore » to the Orthopedic Department for an Ilizarov operation comprising lengthening and axis correction of the left tibia. Arterial hypertension (220/130 mm Hg) was noted, and biochemical studies documented high plasma renin activity and high aldosterone concentrations. Renal studies showed a small left kidney, and angiography showed several intrarenal high-grade stenoses of the left renal artery with poor opacification, and spotted nephrogram of the middle part and upper pole. Partial nephrectomy with removal of the upper and middle poles of the left kidney was performed. Pathological examination of the small and large blood vessels showed marked intimal proliferation and splitting of the elastica. 3 refs.« less

In vivo genotoxicity assessment of acrylamide and glycidyl methacrylate.

PubMed

Dobrovolsky, Vasily N; Pacheco-Martinez, M Monserrat; McDaniel, L Patrice; Pearce, Mason G; Ding, Wei

2016-01-01

Acrylamide (ACR) and glycidyl methacrylate (GMA) are structurally related compounds used for making polymers with various properties. Both chemicals can be present in food either as a byproduct of processing or a constituent of packaging. We performed a comprehensive evaluation of ACR and GMA genotoxicity in Fisher 344 rats using repeated gavage administrations. Clastogenicity was measured by scoring micronucleated (MN) erythrocytes from peripheral blood, DNA damage in liver, bone marrow and kidneys was measured using the Comet assay, and gene mutation was measured using the red blood cell (RBC) and reticulocyte Pig-a assay. A limited histopathology evaluation was performed in order to determine levels of cytotoxicity. Doses of up to 20 mg/kg/day of ACR and up to 250 mg/kg/day of GMA were used. ACR treatment resulted in DNA damage in the liver, but not in the bone marrow. While ACR was not a clastogen, it was a weak (equivocal) mutagen in the cells of bone marrow. GMA caused DNA damage in the cells of bone marrow, liver and kidney, and induced MN reticulocytes and Pig-a mutant RBCs in a dose-dependent manner. Collectively, our data suggest that both compounds are in vivo genotoxins, but the genotoxicity of ACR is tissue specific. Published by Elsevier Ltd.

Acute toxicity study of zerumbone-loaded nanostructured lipid carrier on BALB/c mice model.

PubMed

Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Yeap, Swee Keong; Abdul Samad, Nozlena; Andas, Reena Joys; Muhammad Nadzri, Nabilah; Anasamy, Theebaa; Ng, Kuan Beng; How, Chee Wun

2014-01-01

Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

Space medicine considerations: Skeletal and calcium homeostasis

NASA Technical Reports Server (NTRS)

Schneider, Victor B.

1989-01-01

Based on the information obtained from space missions, particularly Skylab and the longer Salyut missions, it is clear that bone and mineral metabolism is substantially altered during space flight. Calcium balance becomes increasingly more negative throughout the flight, and the bone mineral content of the os calcis declines. The major health hazards associated with skeletal changes include the signs and symptoms of hypercalcemia with rapid bone turnover, the risk of kidney stones because of hypercalciuria, the lengthy recovery of lost bone mass after flight, the possibility of irreversible bone loss (particularly the trabecular bone), the possible effects of metastated calcification in the soft tissues, and the possible increase in fracture potential. For these reasons, major efforts need to be directed toward elucidating the fundamental mechanisms by which bone is lost in space and developing more effective countermeasures to prevent both short-term and long-term complications.

The Biology of Bone Metastasis.

PubMed

Esposito, Mark; Guise, Theresa; Kang, Yibin

2018-06-01

Bone metastasis, or the development of secondary tumors within the bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of bone metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous bone stromal elements to grow into pathological osteolytic or osteoblastic lesions. This colonization process can be separated into three key steps: seeding, dormancy, and outgrowth. Targeting the processes of dormancy and initial outgrowth offers the most therapeutic promise. Here, we discuss the concepts of the bone metastasis niche, from controlling tumor-cell survival to growth into clinically detectable disease. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice.

PubMed

Wood, Su; Petty, Duncan; Glidewell, Liz; Raynor, Dk Theo

2018-05-01

Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft-Gault) gives a more accurate estimate of kidney function. To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft-Gault) was calculated using actual body weight and estimated ideal body weight. Kidney function was too low for recommended prescribing in 4-40% of people aged ≥65 years, and in 24-80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft-Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced. © British Journal of General Practice 2018.

CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors.

PubMed

Barbas, Andrew S; Li, Yanhong; Zair, Murtuza; Van, Julie A; Famure, Olusegun; Dib, Martin J; Laurence, Jerome M; Kim, S Joseph; Ghanekar, Anand

2016-09-01

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.

PubMed

Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y

2010-04-01

The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.

Protein-restricted diets plus keto/amino acids--a valid therapeutic approach for chronic kidney disease patients.

PubMed

Aparicio, Michel; Bellizzi, Vincenzo; Chauveau, Philippe; Cupisti, Adamasco; Ecder, Tevfik; Fouque, Denis; Garneata, Liliana; Lin, Shanyan; Mitch, William E; Teplan, Vladimír; Zakar, Gábor; Yu, Xueqing

2012-03-01

Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Depletion of CD8 Memory T Cells for Induction of Tolerance of a Previously Transplanted Kidney Allograft

PubMed Central

Koyama, I.; Nadazdin, O.; Boskovic, S.; Ochiai, T.; Smith, R. N.; Sykes, M.; Sogawa, H.; Murakami, T.; Strom, T. B.; Colvin, R. B.; Sachs, D. H.; Benichou, G.; Cosimi, A. B.; Kawai, T.

2013-01-01

Heterologous immunologic memory has been considered a potent barrier to tolerance induction in primates. Induction of such tolerance for a previously transplanted organ may be more difficult, because specific memory cells can be induced and activated by a transplanted organ. In the current study, we attempted to induce tolerance to a previously transplanted kidney allograft in nonhuman primates. The conditioning regimen consisted of low dose total body irradiation, thymic irradiation, antithymocyte globulin, and anti- CD154 antibody followed by a brief course of a calcineurin inhibitor. This regimen had been shown to induce mixed chimerism and allograft tolerance when kidney transplantation (KTx) and donor bone marrow transplantation (DBMT) were simultaneously performed. However, the same regimen failed to induce mixed chimerism when delayed DBMT was performed after KTx. We found that significant levels of memory T cells remained after conditioning, despite effective depletion of naïve T cells. By adding humanized anti-CD8 monoclonal antibody (cM-T807), CD8 memory T cells were effectively depleted and these recipients successfully achieved mixed chimerism and tolerance. The current studies provide ‘proof of principle’ that the mixed chimerism approach can induce renal allograft tolerance, even late after organ transplantation if memory T-cell function is adequately controlled. PMID:17286617

H+, Water and Urea Transport in the Inner Medullary Collecting Duct and Their Role in the Prevention and Pathogenesis of Renal Stone Disease

NASA Astrophysics Data System (ADS)

Wall, Susan M.; Klein, Janet D.

2008-09-01

The inner medullary collecting duct (IMCD) is the final site within the kidney for the reabsorption of urea, water and electrolytes and for the secretion of H+ before the luminal fluid becomes the final urine. Transporters expressed in the IMCD contribute to the generation of the large ion gradients that exist between the interstitium and the collecting duct lumen. Thus, the luminal fluid within the human IMCD can reach an osmolality of 1200 mOsm/kg H2O and a pH of 4. This ability of the human nephron to concentrate and acidify the urine might predispose to stone formation. However, under treatment conditions that predispose to stone formation, such as during hypercalciuria, the kidney mitigates stone formation by reducing solute concentration by reducing H2O reabsorption. Moreover, the kidney attenuates stone formation by tightly controlling acid-base balance, which prevents the bone loss, hypocitraturia and hypercalciuria observed during metabolic acidosis by augmenting net H+ excretion by tightly regulating H+ transporter function and through luminal buffering, particularly with NH3. This article will review the ion transporters present in the mammalian IMCD and their role in the prevention and in the pathogenesis of renal stone formation.

Calcium source (image)

MedlinePlus

Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has ... as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also effects the ...

Evaluation of intraperitoneal vincristine in malignant peritoneal effusion.

PubMed

Bairy, K L; Sanath, S; Jagetia, G C; Somayaji, S N; Vidyasagar, M S; Baliga, M S

2003-07-01

The efficacy and safety of intraperitoneal administration of vincristine sulphate was determined in mice bearing Ehrlich ascitic carcinoma. The tumor bearing animals were administered with 0.5 mg/kg body weight (b.wt) of freshly prepared vincristine sulphate intraperitoneally on day 6 after tumor transplantation followed by drug administration once daily 5 days a week consecutively. The observations regarding the survival, alteration in the volume of peritoneal fluid, increase in life span and pathological changes in the liver, kidney, gastrointestinal tract and bone tissues were made. The vincristine sulphate treatment reduced the malignant cell population significantly and there were no significant changes in the histological picture of liver, kidney, bone, except the intestine, where atropy of villi demonstrating nests and cords of uniform small round cells were observed. Our experimental data suggests that intraperitoneal administration of vincristine is beneficial in malignant peritoneal effusion.

[Calciotropic actions of parathyroid hormone and vitamin D-endocrine system].

PubMed

Avila, Euclides; Barrera, David; Díaz, Lorenza

2007-01-01

Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25-(OH)zD] participate in systemic regulation of calcium homeostasis through endocrine effects mediated via the specific receptors PTHR1 and VDR, expressed in bone, kidney, intestine and parathyroid glands. In bone, both hormones PTH and 1,25-(OH)2D promote calcium release into the circulation; however, they also have anabolic effects in this tissue. In kidney, PTH controls 1,25-(OH)2D synthesis, and together both hormones stimulate calcium reabsorption. The most important calciotropic action of 1,25-(OH)2D is stimulation of intestinal calcium absorption. In the parathyroid glands, 1,25-(OH)2D regulates PTH synthesis through a negative feedback mechanism, while modulating the gland growth. Finally, a general overview of the maternal adaptations regarding calcium homeostasis during pregnancy and lactation is presented.

Inactivation of AMMECR1 is associated with growth, bone, and heart alterations.

PubMed

Moysés-Oliveira, Mariana; Giannuzzi, Giuliana; Fish, Richard J; Rosenfeld, Jill A; Petit, Florence; Soares, Maria de Fatima; Kulikowski, Leslie Domenici; Di-Battista, Adriana; Zamariolli, Malú; Xia, Fan; Liehr, Thomas; Kosyakova, Nadezda; Carvalheira, Gianna; Parker, Michael; Seaby, Eleanor G; Ennis, Sarah; Gilbert, Rodney D; Hagelstrom, R Tanner; Cremona, Maria L; Li, Wenhui L; Malhotra, Alka; Chandrasekhar, Anjana; Perry, Denise L; Taft, Ryan J; McCarrier, Julie; Basel, Donald G; Andrieux, Joris; Stumpp, Taiza; Antunes, Fernanda; Pereira, Gustavo José; Neerman-Arbez, Marguerite; Meloni, Vera Ayres; Drummond-Borg, Margaret; Melaragno, Maria Isabel; Reymond, Alexandre

2018-02-01

We report five individuals with loss-of-function of the X-linked AMMECR1: a girl with a balanced X-autosome translocation and inactivation of the normal X-chromosome; two boys with maternally inherited and de novo nonsense variants; and two half-brothers with maternally inherited microdeletion variants. They present with short stature, cardiac and skeletal abnormalities, and hearing loss. Variants of unknown significance in AMMECR1 in four male patients from two families with partially overlapping phenotypes were previously reported. AMMECR1 is coexpressed with genes implicated in cell cycle regulation, five of which were previously associated with growth and bone alterations. Our knockdown of the zebrafish orthologous gene resulted in phenotypes reminiscent of patients' features. The increased transcript and encoded protein levels of AMMECR1L, an AMMECR1 paralog, in the t(X;9) patient's cells indicate a possible partial compensatory mechanism. AMMECR1 and AMMECR1L proteins dimerize and localize to the nucleus as suggested by their nucleic acid-binding RAGNYA folds. Our results suggest that AMMECR1 is potentially involved in cell cycle control and linked to a new syndrome with growth, bone, heart, and kidney alterations with or without elliptocytosis. © 2017 Wiley Periodicals, Inc.

MANAGEMENT OF BILATERAL FEMORAL NECK FRACTURE IN A NONAGENARIAN PATIENT--CASE REPORT.

PubMed

Popescu, D; Trandabaţ, C; Puha, B; Veliceasa, B; Alexa, O

2016-01-01

Simultaneous bilateral femoral neck fracture is rare injury. Cases with this type of fracture have been reported in the literature since the 1950s, following the introduction of electroconvulsive therapy which generates violent hip muscle contractions. In young patients' simultaneous bilateral femoral neck fracture results from high energy trauma (car accident or fall from height) in a normal bone. Pathological changes in bone structure occurring in chronic kidney disease, vitamin D deficiency, osteomalacia, osteoporosis, metabolic imbalances and administration of corticosteroids explain the occurrence of this particular type of fracture following low-energy trauma. We present the case of a 90-year-old female patient who suffered a simple fall from her own height resulting in a Garden IV bilateral femoral neck fracture. Our therapeutic option in this patient was bilateral uncemented bipolar hemiarthroplasty in a single session using a single tray of sterile surgical instruments and two sterile drapes. Postoperative outcome was very good, allowing the initiation of functional recovery on the first postoperative day. Uncemented hemiarthroplasty proved to be a good choice in such a patient in the associated diseases may trigger the risk of cardiovascular disturbances specific to bone cement implantation syndrome.

Differentiation of Mesenchymal Stem Cells Towards Nephrogenic Lineage and Their Enhanced Resistance to Oxygen Peroxide-induced Oxidative Stress.

PubMed

Tayyeb, Asima; Shahzad, Naveed; Ali, Gibran

2017-07-01

Mesenchymal stem cells (MSCs) have been publicized to ameliorate kidney injury both in vitro and in vivo. However, very less is known if MSCs can be differentiated towards renal lineages and their further application potential in kidney injuries. The present study developed a conditioning system of growth factors fibroblast growth factor 2, transforming growth factor-β2, and leukemia inhibitory factor for in vitro differentiation of MSCs isolated from different sources towards nephrogenic lineage. Less invasively isolated adipose-derived MSCs were also compared to bone marrow-derived MSCs for their differentiation potential to induce renal cell. Differentiated MSCs were further evaluated for their resistance to oxidative stress induced by oxygen peroxide. A combination of growth factors successfully induced differentiation of MSCs. Both types of differentiated cells showed significant expression of pronephrogenic markers (Wnt4, Wt1, and Pax2) and renal epithelial markers (Ecad and ZO1). In contrast, expression of mesenchymal stem cells marker Oct4 and Vim were downregulated. Furthermore, differentiated adipose-derived MSCs and bone marrow-derived MSCs showed enhanced and comparable resistance to oxygen peroxide-induced oxidative stress. Adipose-derived MSC provides a promising alternative to bone marrow-derived MSC as a source of autologous stem cells in human kidney injuries. In addition, differentiated MSCs with further in vivo investigations may serve as a cell source for tissue engineering or cell therapy in different renal ailments.

The consequences of pediatric renal transplantation on bone metabolism and growth.

PubMed

Bacchetta, Justine; Ranchin, Bruno; Demède, Delphine; Allard, Lise

2013-10-01

During childhood, growth retardation, decreased final height and renal osteodystrophy are common complications of chronic kidney disease (CKD). These problems remain present in patients undergoing renal transplantation, even though steroid-sparing strategies are more widely used. In this context, achieving normal height and growth in children after transplantation is a crucial issue for both quality of life and self-esteem. The aim of this review is to provide an overview of pathophysiology of CKD-mineral bone disorder (MBD) in children undergoing renal transplantation and to propose keypoints for its daily management. In adults, calcimimetics are effective for posttransplant hyperparathyroidism, but data are missing in the pediatric population. Fibroblast growth factor 23 levels are associated with increased risk of rejection, but the underlying mechanisms remain unclear. A recent meta-analysis also demonstrated the effectiveness of rhGH therapy in short transplanted children. In 2013, the daily clinical management of CKD-MBD in transplanted children should still focus on simple objectives: to optimize renal function, to develop and promote steroid-sparing strategies, to provide optimal nutritional support to maximize final height and avoid bone deformations, to equilibrate calcium/phosphate metabolism so as to provide acceptable bone quality and cardiovascular status, to correct all metabolic and clinical abnormalities that can worsen both bone and growth (mainly metabolic acidosis, anemia and malnutrition), promote good lifestyle habits (adequate calcium intake, regular physical activity, no sodas consumption, no tobacco exposure) and eventually to correct native vitamin D deficiency (target of 25-vitamin D >75 nmol/l).

The science of Stewardship: due diligence for kidney donors and kidney function in living kidney donation--evaluation, determinants, and implications for outcomes.

PubMed

Poggio, Emilio D; Braun, William E; Davis, Connie

2009-10-01

Living kidney donor transplantation is now a common treatment for ESRD because it provides excellent outcomes to transplant recipients and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of this procedure. Whereas the initial experiences with living kidney donors mostly included the healthiest, the increase in the need for organs and the changing demographic characteristics of the general population have subtly reshaped the suitability for donation. Kidney function assessment is a critical component of the evaluation of prospective donors; therefore, special emphasis is usually placed on this aspect of the evaluation. At the same time, consideration of kidney function after donation is important because it assists with the determination of renal health in donors. This review summarizes the process of predonation kidney function assessment, determinants of pre- and postdonation renal function, and, importantly, the potential implications of kidney function to the long-term outcomes of kidney donors.

[Decline in renal function in old age : Part of physiological aging versus age-related disease].

PubMed

Braun, F; Brinkkötter, P T

2016-08-01

The incidence and prevalence of chronic renal disease (CKD) in elderly patients are continuously increasing worldwide. Loss of renal function is not only considered to be part of the aging process itself but also reflects the multimorbidity of many geriatric patients. Calculating the glomerular filtration rate using specific algorithms validated for the elderly population and measuring the amount of proteinuria allow an estimation of renal function in elderly patients with high accuracy. Chronic renal failure has many clinical consequences and not only results in a delayed excretion of toxins cleared by the kidneys but also affects hematogenesis, water and electrolyte balance as well as mineral bone metabolism. Furthermore, CKD directly leads to and aggravates geriatric syndromes and in particular the onset of frailty. Therapeutic strategies to halt progression of CKD not only comprise treatment of the underlying disease but also efficient blood pressure and diabetic control and the avoidance of nephrotoxic medications.

Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial.

PubMed

Garg, Amit X; Devereaux, P J; Yusuf, Salim; Cuerden, Meaghan S; Parikh, Chirag R; Coca, Steven G; Walsh, Michael; Novick, Richard; Cook, Richard J; Jain, Anil R; Pan, Xiangbin; Noiseux, Nicolas; Vik, Karel; Stolf, Noedir A; Ritchie, Andrew; Favaloro, Roberto R; Parvathaneni, Sirish; Whitlock, Richard P; Ou, Yongning; Lawrence, Mitzi; Lamy, Andre

2014-06-04

Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration, which may persist for several days. Such acute kidney injury is associated with lower long-term kidney function. However, it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function. To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later. The Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites in 19 countries. Patients were randomized to receive CABG surgery either with a beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year. The last 1-year serum creatinine concentration was recorded on January 18, 2013. Acute kidney injury within 30 days of surgery (≥50% increase in serum creatinine concentration from prerandomization concentration) and loss of kidney function at 1 year (≥20% loss in estimated glomerular filtration rate from prerandomization level). Off-pump (n = 1472) vs on-pump (n = 1460) CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%, respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there was no significant difference between the 2 groups in the loss of kidney function at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29], P = .23). Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss, and in the subgroup with baseline chronic kidney disease. Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year. In this setting, an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function. clinicaltrials.gov Identifier: NCT00463294.

TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6.

PubMed

van Goor, Mark K C; Hoenderop, Joost G J; van der Wijst, Jenny

2017-06-01

Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture. While this field is still in its infancy, it has increased our understanding of molecular channel regulation and holds great promise for future structure-function studies of these ion channels. This review will summarize the mechanisms that control the systemic calcium balance, as well as extrapolate structural views to the molecular functioning of TRPV5/6 channels in epithelial calcium transport. Copyright © 2016. Published by Elsevier B.V.

Nocturnal Hypoxia and Loss of Kidney Function

PubMed Central

Ahmed, Sofia B.; Ronksley, Paul E.; Hemmelgarn, Brenda R.; Tsai, Willis H.; Manns, Braden J.; Tonelli, Marcello; Klarenbach, Scott W.; Chin, Rick; Clement, Fiona M.; Hanly, Patrick J.

2011-01-01

Background Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year. Results 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67). Conclusion Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function. PMID:21559506

Anemia in patient with primary hyperoxaluria and bone marrow involvement by oxalate crystals.

PubMed

Mykytiv, Vitaliy; Campoy Garcia, Fiz

2018-06-01

We present a rare case of anaemia secondary to bone marrow infiltration by oxalate crystals and renal failure in a patient diagnosed with primary hyperoxaluria. In our case, the anaemia was recovered after the double liver and kidney transplantation, the latter was performed on two occasions after the failure of the first graft. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

A brief review on experimental fluorosis.

PubMed

Perumal, Ekambaram; Paul, Vanaja; Govindarajan, Vimal; Panneerselvam, Lakshmikanthan

2013-11-25

Fluoride (F) is a naturally occurring contaminant in the water. F is essential for normal maintenance of teeth and bones. However, prolonged exposure to high concentration of F is found to be deleterious to teeth, bones and other organs. Besides drinking water, F can enter the body through food, dental products, drugs and industrial emission. People living in areas where F contamination is much higher than the expected level, are found to suffer from not only teeth and bone problem but also other systems, including brain and its functions. Since animals respond to the toxic effects of F like human beings, the deleterious effects of F have been produced experimentally in animals in order to determine the mechanism involved in the action of F. The reports indicating the chronic harmful effects of F in teeth, bones, heart, liver, kidneys, gastrointestinal tract, lungs, brain, blood, hormones and biochemical parameters of experimental animals and in in vitro studies have been reviewed in this article. The neurotoxic action of F that produces chiefly learning and memory impairment has also been included. The review also points out the harmful effects of F on reproduction, its teratogenic action and in inducing premature ageing. Finally, the reports indicating a reversal of certain toxicities of F in experimental animals after withdrawal of its exposure has been included. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Requirement for Class II Phosphoinositide 3-Kinase C2α in Maintenance of Glomerular Structure and Function▿

PubMed Central

Harris, David P.; Vogel, Peter; Wims, Marie; Moberg, Karen; Humphries, Juliane; Jhaver, Kanchan G.; DaCosta, Christopher M.; Shadoan, Melanie K.; Xu, Nianhua; Hansen, Gwenn M.; Balakrishnan, Sanjeevi; Domin, Jan; Powell, David R.; Oravecz, Tamas

2011-01-01

An early lesion in many kidney diseases is damage to podocytes, which are critical components of the glomerular filtration barrier. A number of proteins are essential for podocyte filtration function, but the signaling events contributing to development of nephrotic syndrome are not well defined. Here we show that class II phosphoinositide 3-kinase C2α (PI3KC2α) is expressed in podocytes and plays a critical role in maintaining normal renal homeostasis. PI3KC2α-deficient mice developed chronic renal failure and exhibited a range of kidney lesions, including glomerular crescent formation and renal tubule defects in early disease, which progressed to diffuse mesangial sclerosis, with reduced podocytes, widespread effacement of foot processes, and modest proteinuria. These findings were associated with altered expression of nephrin, synaptopodin, WT-1, and desmin, indicating that PI3KC2α deficiency specifically impacts podocyte morphology and function. Deposition of glomerular IgA was observed in knockout mice; importantly, however, the development of severe glomerulonephropathy preceded IgA production, indicating that nephropathy was not directly IgA mediated. PI3KC2α deficiency did not affect immune responses, and bone marrow transplantation studies also indicated that the glomerulonephropathy was not the direct consequence of an immune-mediated disease. Thus, PI3KC2α is critical for maintenance of normal glomerular structure and function by supporting normal podocyte function. PMID:20974805

Creatinine clearance test

MedlinePlus

Serum creatinine clearance; Kidney function - creatinine clearance; Renal function - creatinine clearance ... the body entirely by the kidneys. If kidney function is abnormal, creatinine level increases in the blood ...

Secondary contributors to bone loss in osteoporosis related hip fractures.

PubMed

Edwards, B J; Langman, C B; Bunta, A D; Vicuna, M; Favus, M

2008-07-01

Osteoporosis treatment of patients with hip fractures is necessary to prevent subsequent fractures. Secondary causes for bone loss are present in more than 80% of patients with hip fractures, and therefore, assessment of Vitamin D status, disorders in calcium absorption and excretion, monoclonal gammopathies, and renal function should be performed. Identifying and managing these disorders will improve detection and enhance treatment aimed at reducing the risk of recurrent fractures in older adults. The purpose of this study was to determine the prevalence of disorders affecting bone and mineral metabolism in individuals with osteoporotic hip fractures. Community dwelling individuals with hip fractures (HFx) 50 years of age and older. Assessment for vitamin D, renal and parathyroid status, calcium absorption, and plasma cell disorders. Of 157 HFx, mean age 70 +/- 10 years, HFx had higher creatinine (p = 0.002, 95% C.I. -0.09, 0.05); lower 25 OH vitamin D (p = 0.019, 95% C.I. 6.5, 2.7), albumin (p = 0.007, 95% C.I. 0.36, 0.009), and 24-h urine calcium (p = 0.024, 95% CI 51, 21) as compared to controls. More than 80% of HFx had at least one previously undiagnosed condition, with vitamin D insufficiency (61%), chronic kidney disease (16%) (CKD), monoclonal gammopathy (6%), and low calcium absorption (5%) being the most common. One case each of multiple myeloma and solitary plasmocytoma were identified. Osteoporosis treatment of HFx is necessary to prevent subsequent fractures. Secondary causes for bone loss are remarkably common in HFx; therefore, assessment of vitamin D status, disorders in calcium absorption and excretion, protein electrophoresis, and renal function should be performed. Identifying and correcting these disorders will improve detection and enhance treatment aimed at reducing the risk of recurrent fractures in older adults.

Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys

PubMed Central

Lawrence, Melanie L.; Chang, C-Hong; Davies, Jamie A.

2015-01-01

Recent advances in renal tissue engineering have shown that dissociated, early renogenic tissue from the developing embryo can self-assemble into morphologically accurate kidney-like organs arranged around a central collecting duct tree. In order for such self-assembled kidneys to be useful therapeutically or as models for drug screening, it is necessary to demonstrate that they are functional. One of the main functional characteristics of mature kidneys is transport of organic anions and cations into and out of the proximal tubule. Here, we show that the transport function of embryonic kidneys allowed to develop in culture follows a developmental time-course that is comparable to embryonic kidney development in vivo. We also demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels. These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys. PMID:25766625

The Importance of Residual Kidney Function in Haemodialysis Patients.

PubMed

Kong, Jessica; Davies, Matthew; Mount, Peter

2018-06-19

In contrast to peritoneal dialysis, residual kidney function is commonly disregarded for haemodialysis patients, and not regularly monitored or taken into account in routine clinical care. This is despite evidence that higher levels of residual kidney function in haemodialysis patients associate with better outcomes including survival, total solute clearance, nutrition, inflammation, and fluid balance. This review aims to summarise the clinical effects of residual kidney function specifically in haemodialysis patients. Some level of residual kidney function is present in over 80% of patients at the time of dialysis initiation, and while this declines over time, up to 30% of patients on haemodialysis for 5 years still have a measurable level of native kidney function. There is little evidence on how best to preserve residual kidney function in haemodialysis patients, although it has been observed that intensive haemodialysis regimens in incident haemodialysis patients appear to accelerate residual kidney function decline. Residual kidney function is not commonly factored in to haemodialysis prescription and measures of adequacy, despite the fact that some guidelines such as KDOQI and European Best Practice Guidelines suggest that it is reasonable to do. This likely relates, at least in part, to perceived concerns regarding the inconvenience of timed urine collections, and to the complexity and lack of consensus regarding the methods for integrating the intermittent clearance of haemodialysis with the continuous clearance of native renal function. Further research is required into how best to maintain and maximise the benefits of residual kidney function in haemodialysis patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Methodological aspects related to the determination of the relative renal function using 99mTC MAG3].

PubMed

Ladrón De Guevara Hernández, D; Ham, H; Franken, P; Piepsz, A; Lobo Sotomayor, G

2002-01-01

The aim of the study was to evaluate three different methods for calculating the split renal function in patients with only one functioning kidney, keeping in mind that the split function should be zero on the side of the non-functioning kidney. We retrospectively selected 28 99mTc MAG3 renograms performed in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12 with a non-functioning kidney. A renal and perirenal region of interest (ROI) were delineated around the functioning kidney. The ROIs around the empty kidney were drawn symmetrically to the contralateral side. The split renal function was calculated using three different methods, the integral method, the slope method and the Patlak-Rutland algorithm. For the whole group of 28 kidneys as well as for the three categories of patients, the three methods provided a split function on the side of the non-functioning kidney close to the zero value, regardless of whether the empty kidney was the left or the right one. We recommend the use of the integral method for the whole range of split renal function with 99mTc MAG3. No significant improvement was obtained by means of the more sophisticated Patlak-Rutland method.

Corrective effects of acerola (Malpighia emarginata DC.) juice intake on biochemical and genotoxical parameters in mice fed on a high-fat diet.

PubMed

Leffa, Daniela Dimer; da Silva, Juliana; Daumann, Francine; Dajori, Ana Luiza Formentin; Longaretti, Luiza Martins; Damiani, Adriani Paganini; de Lira, Fabio; Campos, Fernanda; Ferraz, Alexandre de Barros Falcão; Côrrea, Dione Silva; de Andrade, Vanessa Moraes

2014-12-01

Acerola contains high levels of vitamin C and rutin and shows the corresponding antioxidant properties. Oxidative stress on the other hand is an important factor in the development of obesity. In this study, we investigated the biochemical and antigenotoxic effects of acerola juice in different stages of maturity (unripe, ripe and industrial) and its main pharmacologically active components vitamin C and rutin, when given as food supplements to obese mice. Initial HPLC analyses confirmed that all types of acerola juice contained high levels of vitamin C and rutin. DPPH tests quantified the antioxidant properties of these juices and revealed higher antioxidant potentials compared to pure vitamin C and rutin. In an animal test series, groups of male mice were fed on a standard (STA) or a cafeteria (CAF) diet for 13 weeks. The latter consisted of a variety of supermarket products, rich in sugar and fat. This CAF diet increased the feed efficiency, but also induced glucose intolerance and DNA damage, which was established by comet assays and micronucleus tests. Subsequently, CAF mice were given additional diet supplements (acerola juice, vitamin C or rutin) for one month and the effects on bone marrow, peripheral blood, liver, kidney, and brain were examined. The results indicated that food supplementation with ripe or industrial acerola juice led to a partial reversal of the diet-induced DNA damage in the blood, kidney, liver and bone marrow. For unripe acerola juice food supplementation, beneficial effects were observed in blood, kidney and bone marrow. Food supplementation with vitamin C led to decreased DNA damage in kidney and liver, whereas rutin supplementation led to decreased DNA damage in all tissue samples observed. These results suggest that acerola juice helps to reduce oxidative stress and may decrease genotoxicity under obesogenic conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Lymphocyte Infusion in Treating Patients With Relapsed Cancer After Bone Marrow or Peripheral Stem Cell Transplantation

ClinicalTrials.gov

2011-11-28

Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

Light-Emitting Diode Therapy in Preventing Mucositis in Children Receiving Chemotherapy With or Without Radiation Therapy Before Bone Marrow Transplantation

ClinicalTrials.gov

2013-09-19

Chronic Myeloproliferative Disorders; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Oral Complications; Ovarian Cancer; Pain; Sarcoma

Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

ClinicalTrials.gov

2017-05-15

Childhood Acute Lymphoblastic Leukemia; Childhood Rhabdomyosarcoma; Childhood Soft Tissue Sarcoma; Ewing Sarcoma; Ewing Sarcoma of Bone; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Unspecified Childhood Solid Tumor, Protocol Specific; Wilms Tumor and Other Childhood Kidney Tumors

Characterization of renal amyloid derived from the variable region of the lambda light chain subgroup II.

PubMed Central

Picken, M. M.; Gallo, G.; Buxbaum, J.; Frangione, B.

1986-01-01

Amyloid fibrils were extracted from the kidney of a patient (CHE) shown to have tetramers and dimers of a monoclonal lambda light chain in his serum, and whose bone marrow cells in short-term culture synthesized these forms and a smaller lambda fragment of approximately 10,000 to 12,000 daltons. Biochemical and serologic analysis of a fraction of a size (obtained from amyloid fibrils extracted from the kidney) similar to that synthesized by the bone marrow cells revealed a light chain fragment corresponding to the amino terminal end of the variable region of the lambda light chain subgroup II. The presence of similarly sized short fragments of lambda light chain in both the synthesized and deposited protein suggests that aberrant synthesis and/or proteolytic degradation may play a pathogenetic role in the process of amyloidogenesis. Images Figure 1 PMID:3089021

Reducing the Dietary Acid Load: How a More Alkaline Diet Benefits Patients With Chronic Kidney Disease.

PubMed

Passey, Caroline

2017-05-01

It has been proposed that a low-protein diet will slow progression of chronic kidney disease although studies have not always supported this belief. The accepted practice is that 60% to 70% of protein comes from high biological value (HBV) protein, but this limits patient choice and patients struggle to follow the diet. When a diet with only 30% HBV protein was trialed, there was a significant increase in serum bicarbonate, and patients preferred the diet. The dietary advice given in predialysis clinics was changed. HBV protein was restricted to approximately 50% of total protein, bread and cereal foods were allowed freely, and fruits and vegetables (F&V) were encouraged. Patients who followed the diet have seen a slowing of progression and occasionally regression of their renal function. Both observations and scientific literature indicate that this is because of a reduction in the acid content of the diet. When foods are metabolized, most proteins produce acid, and most F&V produce alkali. A typical 21 st -century diet produces 50 to 100 mEq H + per day which the kidney is challenged to excrete. Acid is excreted with phosphate and is limited to about 45 mEq H + per day. With chronic kidney disease, this falls progressively to below 20 mEq H + per day. Historically, ammonium excretion was believed to be excretion of acid (NH 3 +  + H + → NH 4 + ), but it is now understood to be a by-product in the neutralization of acid by glutamine. The remaining acid is neutralized or stored within the body. Bone and muscle are lost in order to neutralize the acid. Acid also accumulates within cells, and serum bicarbonate falls. The author postulates that reducing the acid load through a low-protein diet with greater use of vegetable proteins and increased F&V intake will slow progression or occasionally improve renal function while maintaining the nutritional status of the individual. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model

PubMed Central

Herrero, Esther; Torras, Joan; Ripoll, Elia; Flaquer, Maria; Gomà, Montse; Lloberas, Nuria; Anegon, Ignacio; Cruzado, Josep M.; Grinyó, Josep M.; Herrero-Fresneda, Immaculada

2012-01-01

In solid organ transplantation, mesenchymal stem cell (MSC) therapy is strongly emerging among other cell therapies due to the positive results obtained in vitro and in vivo as an immunomodulatory agent and their potential regenerative role. We aimed at testing whether a single dose of MSCs, injected at 11 weeks after kidney transplantation for the prevention of chronic mechanisms, enhanced regeneration and provided protection against the inflammatory and fibrotic processes that finally lead to the characteristic features of chronic allograft nephropathy (CAN). Either bone marrow mononuclear cells (BMCs) injection or no-therapy (NT) were used as control treatments. A rat kidney transplantation model of CAN with 2.5 h of cold ischemia was used, and functional, histological, and molecular parameters were assessed at 12 and 24 weeks after transplantation. MSC and BMC cell therapy preserves renal function at 24 weeks and abrogates proteinuria, which is typical of this model (NT24w: 68.9±26.5 mg/24 h, MSC24w: 16.6±2.3 mg/24 h, BMC24w: 24.1±5.3 mg/24 h, P<0.03). Only MSC-treated animals showed a reduction in interstitial fibrosis and tubular atrophy (NT24w: 2.3±0.29, MSC24w: 0.4±0.2, P<0.03), less T cells (NT: 39.6±9.5, MSC: 8.1±0.9, P<0.03) and macrophages (NT: 20.9±4.7, MSC: 5.9±1.7, P<0.05) infiltrating the parenchyma and lowered expression of inflammatory cytokines while increasing the expression of anti-inflammatory factors. MSCs appear to serve as a protection from injury development rather than regenerate the damaged tissue, as no differences were observed in Ki67 expression, and kidney injury molecule-1, Clusterin, NGAL, and hepatocyte growth factor expression were only up-regulated in nontreated animals. Considering the results, a single delayed MSC injection is effective for the long-term protection of kidney allografts. PMID:22494435

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

PubMed

Andreu Cayuelas, Jose Manuel; Caro Martínez, Cesar; Flores Blanco, Pedro Jose; Elvira Ruiz, Gines; Albendin Iglesias, Helena; Cerezo Manchado, Juan Jose; Bailen Lorenzo, Jose Luis; Januzzi, James L; García Alberola, Arcadio; Manzano-Fernández, Sergio

2018-06-01

Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Bisphosphonates for prevention of osteopenia in kidney-transplant recipients: a systematic review of randomized controlled trials.

PubMed

Wang, J; Yao, M; Xu, J-h; Shu, B; Wang, Y-j; Cui, X-j

2016-05-01

We conducted a systematic review of randomized controlled trials (RCTs) of bisphosphonates for the prevention of osteopenia in kidney-transplant recipients. Bisphosphonates improved bone mineral density at the lumbar spine and femoral neck after 12 months. However, additional well-designed RCTs are required to determine the optimal treatment strategy. Osteopenic-osteoporotic syndrome is a bone complication of renal transplantation. Bisphosphonates, calcitonin, and vitamin D analogs may be used to prevent or treat osteoporosis or bone loss after renal transplantation. However, there is currently no widely recognized strategy for the prevention of corticosteroid-induced osteoporosis. This study aims to assess the available evidence to guide the targeted use of bisphosphonates for reducing osteoporosis and bone loss in renal-transplant recipients. We searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE for randomized controlled trials of bisphosphonates for osteoporosis or bone loss after renal transplantation. A total of 352 abstracts were identified, of which 55 were considered for evaluation and 9 were included in the final analysis. The primary outcome measure was change in the bone mineral density (BMD) of the lumbar spine and femoral neck after 12 months. Data extraction was performed independently by two investigators. BMD at the lumbar spine was improved after treatment with bisphosphonates [9 trials; 418 patients; weighted mean difference (WMD), 0.61; 95 % confidence interval (CI), 0.16-1.06]. Eight trials (406 patients) that reported changes in BMD at the femoral neck also showed improved outcomes after treatment with bisphosphonates (WMD, 0.06; 95 % CI, 0.03-0.09). Bisphosphonates improve BMD at the lumbar spine and femoral neck after 12 months in renal-transplant recipients.

Combination treatment with whole body vibration and a kidney-tonifying herbal Fufang prevent osteoporosis in ovariectomized rats.

PubMed

Wei, Qiu-shi; Wang, Hai-bin; Wang, Jun-ling; Fang, Bin; Zhou, Guang-quan; Tan, Xin; He, Wei; Deng, Wei-min

2015-02-01

To assess the ability of whole body vibration (WBV) with the kidney-tonifying herbal Fufang (Bushen Zhuanggu Granules, BZG) to prevent osteoporosis in ovariectomized rats. Fifty 6-month-old female Sprague Dawley rats were divided into five groups: sham-operated (SHAM), ovariectomized (OVX), OVX with WBV (OVX + WBV), OVX with BZG (OVX + BZG), OVX with both WBV and BZG (OVX + WBV + BZG). The SHAM group received normal saline. After 12 weeks of treatment, the rats were killed, their serum concentrations of osteopontin (OPN), receptor activator of nuclear factor kappa-B ligand RANKL and bone turnover markers assayed and bone mineral density (BMD), histomorphometry and bone strength evaluated. Concentrations of OPN were significantly lower in the SHAM, OVX + WBV and OVX + WBV + BZG groups at 12 weeks, whereas concentrations of RANKL had decreased significantly in the SHAM, OVX + WBV, OVX + BZG and OVX + WBV + BZG groups. In the OVX + WBV, OVX + BZG and OVX + WBV + BZG groups the amount of bone turnover had been significantly antagonized. Compared with OVX group, BMD, % trabecular area (Tb.Ar), number of trabeculae (Tb.N) and assessed biomechanical variables were higher in OVX+WBV group, whereas and BMD, %Tb.Ar, Tb.N, maximal load and yield load were higher in the OVX + BZG group. All tested indices were significantly lower in the OVX + WBV and OVX + BZG groups than in the OVX + WBV + BZG group. Either WBV or BZG alone prevents OVX-induced bone loss. However, BZG enhances the effect of WBV by further enhancing BMD, bone architecture and strength. © 2015 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney.

PubMed

Nordholm, Anders; Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob; Morevati, Marya; Olgaard, Klaus; Lewin, Ewa

2018-05-01

In a new paradigm of etiology related to chronic kidney disease-mineral and bone disorder (CKD-MBD), kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while activin A might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in the obstructed kidney, untouched contralateral kidney, and vasculature which might be affected by secreted factors from the obstructed kidney, and comparing with unilateral nephrectomized controls (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas plasma Klotho increased in both UUO and UNX rats, indicating an altered metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of Klotho and maintained normal expression of the examined fibrosis-related genes, as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor-β and induction of periostin and activin A in obstructed kidneys without changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after 10 days while no changes were seen in UNX rats, suggesting secretion of activin A from the obstructed kidney with potentially systemic effects on CKD-MBD. As such, increased aortic sclerostin was observed in UUO rats compared with UNX and normal controls. The present results are in line with the new paradigm and show very early vascular effects of unilateral kidney fibrosis, supporting the existence of a new kidney-vasculature axis.

Integral pharmacological management of bone mineral disorders in chronic kidney disease (part I): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification.

PubMed

Bover, J; Ureña-Torres, P; Lloret, M J; Ruiz-García, C; DaSilva, I; Diaz-Encarnacion, M M; Mercado, C; Mateu, S; Fernández, E; Ballarin, J

2016-06-01

Chronic kidney disease-mineral and bone disorders (CKD-MBD), involving a triad of laboratory and bone abnormalities, and tissue calcifications, are associated with dismal hard-outcomes. In two comprehensive articles, we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (this part 1) and hyperparathyroidism (part 2), taking into account CKD-accelerated atheromatosis/atherosclerosis and/or cardiovascular calcification (CVC) processes. Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Individualization of treatment with P-binders and combinations of anti-parathyroid agents may improve biochemical control with lower incidence of undesirable effects. Isolated biochemical parameters do not accurately reflect calcium or P load or bone activity and do not stratify high cardiovascular risk patients with CKD. Initial guidance is provided on reasonable therapeutic strategies which consider the presence of CVC. This part reflects that although there is not an absolute evidence, many studies point to the need to improve P imbalance while trying to, at least, avoid progression of CVC by restriction of Ca-based P-binders if economically feasible. The availability of new drugs (i.e. inhibitors of intestinal transporters), and studies including early CKD should ultimately lead to clearer and more cost/effective clinical targets for CKD-MBD.

The effect of carbon dioxide on the twinkling artifact in ultrasound imaging of kidney stones: A pilot study

PubMed Central

Simon, Julianna C.; Wang, Yak-Nam; Cunitz, Bryan W.; Thiel, Jeffrey; Starr, Frank; Liu, Ziyue; Bailey, Michael R.

2016-01-01

Bone demineralization, dehydration, and stasis put astronauts at an increased risk of forming kidney stones in space. The color-Doppler ultrasound “twinkling artifact”, which highlights kidney stones with color, can make stones readily detectable with ultrasound; however our previous results suggest twinkling is caused by microbubbles on the stone surface which could be affected by the elevated levels of carbon dioxide found on space vehicles. Four pigs were implanted with kidney stones and imaged with ultrasound while the anesthetic carrier gas oscillated between oxygen and air containing 0.8% carbon dioxide. Upon exposing pigs to 0.8% carbon dioxide, twinkling was significantly reduced after 9–25 minutes and recovered when the carrier gas returned to oxygen. These trends repeated when pigs were again exposed to 0.8% carbon dioxide followed by oxygen. The reduction of twinkling from exposure to elevated carbon dioxide may make kidney stone detection with twinkling difficult in current space vehicles. PMID:28190622

Cell metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

NASA Astrophysics Data System (ADS)

Milgram, S.; Carrière, M.; Thiebault, C.; Berger, P.; Khodja, H.; Gouget, B.

2007-07-01

Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se IV and Cu as the most toxic and Ni, Se VI, Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS.

Genome wide identification, phylogeny, and expression of bone morphogenetic protein genes in tetraploidized common carp (Cyprinus carpio).

PubMed

Chen, Lin; Dong, Chuanju; Kong, Shengnan; Zhang, Jiangfan; Li, Xuejun; Xu, Peng

2017-09-05

Bone morphogenetic proteins (Bmps) are a group of signaling molecules known to play important roles during formation and maintenance of various organs, not only bone, but also muscle, blood and so on. Common carp (Cyprinus carpio) is one of the most intensively studied fish due to its economic and environmental importance. Besides, common carp has encountered an additional round of whole genome duplication (WGD) compared with many closely related diploid teleost, which make it one of the most important models for genome evolutionary studies in teleost. Comprehensive genome resources of common carp have been developed recently, which facilitate the thorough characterization of bmp gene family in the tetraploidized common carp genome. We identified a total of 44 bmps from the common carp genome, which are twice as many as that of zebrafish. Phylogenetic analysis revealed that most of bmps are highly conserved. Comparative analysis was performed across six typical vertebrate genomes. It appeared that all the bmp genes in common carp were duplicated. Obviously, the expansion of the bmp gene family in common carp was due to the latest additional round of whole genome duplication and made it more abundant than other diploid teleosts. Expression signatures were assessed in major tissues, including gill, intestine, liver, spleen, skin, heart, gonad, muscle, kidney, head kidney, brain and blood, which demonstrated the comprehensive expression profiles of bmp genes in the tetraploidized genome. Significant gene expression divergences were observed which revealed substantial functional divergences of those duplicated bmp genes post the latest WGD event. The conserved synteny blocks of bmp5s revealed the genome rearrangement of common carp post the 4R WGD. The whole set of bmp gene family in common carp provides insight into gene fate of tetraploidized common carp genome post recent WGD. Copyright © 2017. Published by Elsevier B.V.

Effects of gentamicin and monomer on bone. An in vitro study

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

Pedersen, J.G.; Lund, B.

1988-01-01

Gentamicin-loaded bone cement is used with increasing frequency in primary and revision arthroplasty. Considering the high local concentration and the well-known toxic effect of gentamicin on the kidney, a similar inhibiting effect on bone tissue might be expected. In a series of in vitro studies using paired mouse calvaries cultured for 2 days, the authors found a dose-dependent decrease in the release of previously incorporated calcium-45 (UVCa) or tritiated proline and a decrease in alkaline phosphatase activity. In combination with methylmethacrylate, a small additional reduction in UVCa release and a marked decrease in alkaline phosphatase activity were recorded. These resultsmore » indicate that released gentamicin and monomer from antibiotic-supplemented bone cement depresses bone turnover and might thus play an important part in the pathogenesis of loosening.« less

The Impact of Type 2 Diabetes on Bone Fracture Healing

PubMed Central

Marin, Carlos; Luyten, Frank P.; Van der Schueren, Bart; Kerckhofs, Greet; Vandamme, Katleen

2018-01-01

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease known by the presence of elevated blood glucose levels. Nowadays, it is perceived as a worldwide epidemic, with a very high socioeconomic impact on public health. Many are the complications caused by this chronic disorder, including a negative impact on the cardiovascular system, kidneys, eyes, muscle, blood vessels, and nervous system. Recently, there has been increasing evidence suggesting that T2DM also adversely affects the skeletal system, causing detrimental bone effects such as bone quality deterioration, loss of bone strength, increased fracture risk, and impaired bone healing. Nevertheless, the precise mechanisms by which T2DM causes detrimental effects on bone tissue are still elusive and remain poorly studied. The aim of this review was to synthesize current knowledge on the different factors influencing the impairment of bone fracture healing under T2DM conditions. Here, we discuss new approaches used in recent studies to unveil the mechanisms and fill the existing gaps in the scientific understanding of the relationship between T2DM, bone tissue, and bone fracture healing. PMID:29416527

Regulation of erythropoiesis by hypoxia-inducible factors

PubMed Central

Haase, Volker H.

2012-01-01

A classic physiologic response to systemic hypoxia is the increase in red blood cell production. Hypoxia-inducible factors (HIFs) orchestrate this response by inducing cell-type specific gene expression changes that result in increased erythropoietin (EPO) production in kidney and liver, in enhanced iron uptake and utilization and in adjustments of the bone marrow microenvironment that facilitate erythroid progenitor maturation and proliferation. In particular HIF-2 has emerged as the transcription factor that regulates EPO synthesis in the kidney and liver and plays a critical role in the regulation of intestinal iron uptake. Its key function in the hypoxic regulation of erythropoiesis is underscored by genetic studies in human populations that live at high-altitude and by mutational analysis of patients with familial erythrocytosis. This review provides a perspective on recent insights into HIF-controlled erythropoiesis and iron metabolism, and examines cell types that have EPO-producing capability. Furthermore, the review summarizes clinical syndromes associated with mutations in the O2-sensing pathway and the genetic changes that occur in high altitude natives. The therapeutic potential of pharmacologic HIF activation for the treatment of anemia is discussed. PMID:23291219

Effect of risedronate on bone in renal transplant recipients.

PubMed

Coco, Maria; Pullman, James; Cohen, Hillel W; Lee, Sally; Shapiro, Craig; Solorzano, Clemencia; Greenstein, Stuart; Glicklich, Daniel

2012-08-01

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.

Degradation and silicon excretion of the calcium silicate bioactive ceramics during bone regeneration using rabbit femur defect model.

PubMed

Lin, Kaili; Liu, Yong; Huang, Hai; Chen, Lei; Wang, Zhen; Chang, Jiang

2015-06-01

The investigation of the bone regeneration ability, degradation and excretion of the grafts is critical for development and application of the newly developed biomaterials. Herein, the in vivo bone-regeneration, biodegradation and silicon (Si) excretion of the new type calcium silicate (CaSiO3, CS) bioactive ceramics were investigated using rabbit femur defect model, and the results were compared with the traditional β-tricalcium phosphate [β-Ca3(PO4)2, β-TCP] bioceramics. After implantation of the scaffolds in rabbit femur defects for 4, 8 and 12 weeks, the bone regenerative capacity and degradation were evaluated by histomorphometric analysis. While urine and some organs such as kidney, liver, lung and spleen were resected for chemical analysis to determine the excretion of the ionic products from CS implants. The histomorphometric analysis showed that the bioresorption rate of CS was similar to that of β-TCP in femur defect model, while the CS grafts could significantly stimulate bone formation capacity as compared with β-TCP bioceramics (P < 0.05). The chemical analysis results showed that Si concentration in urinary of the CS group was apparently higher than that in control group of β-TCP. However, no significant increase of the Si excretion was found in the organs including kidney, which suggests that the resorbed Si element is harmlessly excreted in soluble form via the urine. The present studies show that the CS ceramics can be used as safe, bioactive and biodegradable materials for hard tissue repair and tissue engineering applications.

A predictable but life-threatening complication of hydroxyurea in a patient with sickle cell anaemia: an experience learned from a Jehovah's Witness.

PubMed

Tun, Aung Myint; Naing, Ei Ei; Tun, Nay Min; Guevara, Elizabeth

2015-09-30

It is well known that hydroxyurea can cause pancytopaenia secondary to bone marrow suppression, which is reversible with short-term discontinuation of the therapy. However, it is important to note that bone marrow suppressive effects caused by hydroxyurea could be easily potentiated in patients with sickle cell anaemia complicated by chronic kidney disease (CKD). We present a case of a Jehovah's Witness with sickle cell anaemia, who developed severe bone marrow suppression due to the combined effects of hydroxyurea and CKD, resulting in a prolonged recovery period after discontinuation of hydroxyurea. 2015 BMJ Publishing Group Ltd.

Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

PubMed Central

Dabora, Sandra L.; Franz, David Neal; Ashwal, Stephen; Sagalowsky, Arthur; DiMario, Francis J.; Miles, Daniel; Cutler, Drew; Krueger, Darcy; Uppot, Raul N.; Rabenou, Rahmin; Camposano, Susana; Paolini, Jan; Fennessy, Fiona; Lee, Nancy; Woodrum, Chelsey; Manola, Judith; Garber, Judy; Thiele, Elizabeth A.

2011-01-01

Background Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2. Methods We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas. Results 36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1–2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline). Conclusions Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC. Trial Registration Clinicaltrials.gov NCT00126672 PMID:21915260

Kidney function tests

MedlinePlus

Kidney function tests are common lab tests used to evaluate how well the kidneys are working. Such tests include: ... Oh MS, Briefel G. Evaluation of renal function, water, electrolytes ... and Management by Laboratory Methods . 23rd ed. Philadelphia, ...

Cyclosporine and Vancomycin + Amikacin Induced Hot Kidney Appearance in a Young Adult and a Pediatric Patient.

PubMed

Çayır, Derya; Araz, Mine; Filik, Mustafa; Erdoğan, Mehmet

2017-10-03

The appearance of a hot kidney on bone scintigraphy is rare and can be seen due to various factors. In our clinic, we observed hot kidney appearance in two patients to whom technetium-99m methylene diphosphonate (Tc-99m MDP) whole body scan has been performed: a young male adult at the age of 18 who was diagnosed with acute lymphocytic leukemia with a presumptive diagnosis of avascular necrosis, and a 9-year-old girl with cystitis for a pre-diagnosis of osteomyelitis. The first patient had a history of cyclosporine usage and the second patient was being treated with amikacin + vancomycin. To the best of our knowledge, we present the first cases where hot-kidney appearance on Tc-99m MDP whole body scan due to the use of cyclosporin and amikacin + vancomycin is demonstrated.

Breast cancer metastatic to the kidney with renal vein involvement.

PubMed

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

2015-02-01

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

Cystic fibrosis: a clinical view.

PubMed

Castellani, Carlo; Assael, Baroukh M

2017-01-01

Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

Imaging regional renal function parameters using radionuclide tracers

NASA Astrophysics Data System (ADS)

Qiao, Yi

A compartmental model is given for evaluating kidney function accurately and noninvasively. This model is cast into a parallel multi-compartment structure and each pixel region (picture element) of kidneys is considered as a single kidney compartment. The loss of radionuclide tracers from the blood to the kidney and from the kidney to the bladder are modelled in great detail. Both the uptake function and the excretion function of the kidneys can be evaluated pixel by pixel, and regional diagnostic information on renal function is obtained. Gamma Camera image data are required by this model and a screening test based renal function measurement is provided. The regional blood background is subtracted from the kidney region of interest (ROI) and the kidney regional rate constants are estimated analytically using the Kuhn-Pucker multiplier method in convex programming by considering the input/output behavior of the kidney compartments. The detailed physiological model of the peripheral compartments of the system, which is not available for most radionuclide tracers, is not required in the determination of the kidney regional rate constants and the regional blood background factors within the kidney ROI. Moreover, the statistical significance of measurements is considered to assure the improved statistical properties of the estimated kidney rate constants. The relations between various renal function parameters and the kidney rate constants are established. Multiple renal function measurements can be found from the renal compartmental model. The blood radioactivity curve and the regional (or total) radiorenogram determining the regional (or total) summed behavior of the kidneys are obtained analytically with the consideration of the statistical significance of measurements using convex programming methods for a single peripheral compartment system. In addition, a new technique for the determination of 'initial conditions' in both the blood compartment and the kidney compartment is presented. The blood curve and the radiorenogram are analyzed in great detail and a physiological analysis from the radiorenogram is given. Applications of Kuhn-Tucker multiplier methods are illustrated for the renal compartmental model in the field of nuclear medicine. Conventional kinetic data analysis methods, the maximum likehood method, and the weighted integration method are investigated and used for comparisons. Moreover, the effect of the blood background subtraction is shown by using the gamma camera images in man. Several functional images are calculated and the functional imaging technique is applied for evaluating renal function in man quantitatively and visually and compared with comments from a physician.

Contribution of HIF-1alpha or HIF-2alpha to erythropoietin expression: in vivo evidence based on chromatin immunoprecipitation.

PubMed

Yeo, Eun-Jin; Cho, Young-Suk; Kim, Myung-Suk; Park, Jong-Wan

2008-01-01

Circulating erythropoietin (EPO) is mainly produced by the kidneys and mediates erythrogenesis in bone marrow and nonhematopoietic cell survival. EPO is also produced in other tissues where it functions as a paracrine. Moreover, the hypoxic induction of EPO is known to be mediated by HIF-1alpha and HIF-2alpha, but it remains obscure as to which of these two mediators mainly contributes to EPO expression. Thus, we designed in vivo experiments to evaluate the contributions made by HIF-1alpha and HIF-2alpha to EPO expression. In mice exposed to mild whole body hypoxia, HIF-1alpha and HIF-2alpha were both induced in all tissues examined. However, EPO mRNA was expressed in kidney and brain, but not in liver and lung. Likewise, chromatin immunoprecipitation (CHIP) analyses demonstrated that HIF-1alpha or HIF-2alpha binding to the EPO gene increased under hypoxic conditions only in kidney and brain. A comparison of CHIP data and EPO mRNA levels suggested that, during mild hypoxia, renal EPO transcription is induced equally by HIF-1alpha and HIF-2alpha, but that brain EPO is mainly induced during hypoxia by HIF-2alpha. Thus, HIF-1alpha and HIF-2alpha appear to contribute to EPO expression tissue specifically.

Influence of space flight conditions on phenotypes and functionality of nephritic immune cells of fish (Xiphophorus helleri)

NASA Astrophysics Data System (ADS)

Piepenbreier, K.; Renn, J.; Fischer, R.; Goerlich, R.

Microgravity is considered to directly perturb a number of immunological and haematological parameters in mammalians, and therefore is of fundamental importance in space biology. The viviparous teleost Xiphophorus helleri (swordtail) was used as a "lower vertebrate model" in the shuttle missions STS-89 (Small Payload) and STS-90 (NEUROLAB). When developing a regenerative aquatic system (like the Closed Equilibrated Biological Aquatic System - C.E.B.A.S.) to produce food fish on long-term space missions, we have to make sure that microgravity and other space conditions do not endanger the animals' health. Immunological aspects are very important in this field. The major research targets were immunological research of accessory (monocytes) and immunoreactive cells (lymphocytes) of the kidney from X. helleri, which were exposed to microgravity in comparison to ground control animals. Cell cycle analysis of the main haematopoetic organ (kidney), cell behaviour, cell cytochemistry, phagocytic ability and in vitro stimulation of immunoreactive cells from kidney after return to earth were investigated. The results are also important for basic research in immunotoxicology and developmental biology. As there is an interrelation between immune cells and bone metabolism, the investigations are also interesting for space medicine. Acknowledgement: This work was supported by the German Aerospace Center (DLR) (50 WB 9412, 50 WB 9996) and the National Aeronautics and Space Administration (NASA 98HEDS-02-418)

Asymptomatic Kidney Stones in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

PubMed Central

Thomas, Nicole A.; Rai, Shesh N.; Cheon, Kyeongmi; McCammon, Elizabeth; Chesney, Russell; Jones, Deborah; Pui, Ching-Hon; Hudson, Melissa M.

2009-01-01

We hypothesized an association between renal calculi and bone mineral density (BMD) deficits, shown in adults, exists in survivors of childhood ALL. Thus, we analyzed associations between quantitative computed tomography (QCT)-determined renal calcifications and clinical parameters (gender, race, age at diagnosis, age at time of QCT), BMD, treatment exposures, Tanner stage. We investigated associations between stone formation and nutritional intake, serum and urinary calcium and creatinine levels, and urinary calcium/creatinine ratio. Exact Chi-square test was used to compare categorical patient characteristics and Wilcoxon-Mann-Whitney test to compare continuous measurements. Of 424 participants, 218 (51.4%) were male; 371 (87.5%) were non-black. Most (n=270; 63.7%) were ≥ 3.5 years at ALL diagnosis. Mean (SD) and median (range) BMD Z-scores of the entire cohort was -0.4 (1.2) and -0.5 (-3.9 to 5.1), respectively. Nineteen (10 males; 10 Caucasians) had kidney stones (observed prevalence of 4.5 %; 19/424) with significant negative association between stone formation and body habitus (BMI, p=0.003). Stone formation was associated with treatment protocol (p=0.009) and treatment group (0.007). Thus, kidney stones in childhood ALL survivors could herald future deterioration of renal function and development of hypertension. Long-term follow-up imaging may be warranted in these patients to monitor for progressive morbidity. PMID:18830261

HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS

PubMed Central

Rapaport, F. T.; Watanabe, K.; Cannon, F. D.; Mollen, N.; Blumenstock, D.; Ferrebee, J. W.

1972-01-01

17 Cooperstown beagles of known DL-A genotypes were exposed to supralethal total body irradiation and received a bone marrow allograft from a DL-A-identical donor; 11 littermate and 6 nonlittermate donor-recipient pairs were studied. The recipients are surviving uneventfully for 315, 364, 424, 440, 531, 531, 584, 605, 625, 635, and 649 days in the littermate group and for 211, 279, 280, 368, 479, and 480 days in the nonlittermate group. The radiation chimeras underwent bilateral nephrectomy and received a kidney allograft obtained from their respective marrow donor within 43–120 days after bone marrow transplantation. The renal allografts are surviving for 191, 200, 221, 234, 313, 349, 361, 377, 378, 405, 441, 444, 482, 557, 580, 581, and 586 days, respectively. 12 of 13 skin allografts obtained from the marrow donor are at present surviving in the recipients for 107, 110, 110, 110, 116, 122, 128, 143, 143, 162, 178, and 199 days, respectively; one graft was rejected at 84 days. In contrast, the radiation chimeras rejected 25 skin allografts obtained from DL-A-incompatible donors within 10.5–21 days (MST = 15.2 days). Skin transplants obtained from DL-A-identical siblings of the bone marrow donors were rejected within 20–36 days (MST = 25.8 days) in recipients of bone marrow cells obtained from littermate donors. Recipients of nonlittermate bone marrow transplants accorded such allografts a prolonged survival time of 27–76 days (MST = 56.2 days). Prospective selection of genotypically DL-A-identical donor-recipient pairs results in the regularly reproducible long-term survival of bone marrow allografts. The radiation chimeras produced in this manner have developed a donor-specific state of unresponsiveness to kidney and skin allografts. The results are consistent with the existence in the canine species of at least three closely linked genetic systems relevant to transplantation, including DL-A, MLC, and a possible bone marrow transplantation locus. PMID:4404277

Intra-renal arterial injection of autologous bone marrow mesenchymal stromal cells ameliorates cisplatin-induced acute kidney injury in a rhesus Macaque mulatta monkey model.

PubMed

Moghadasali, Reza; Azarnia, Mahnaz; Hajinasrollah, Mostafa; Arghani, Hassan; Nassiri, Seyed Mahdi; Molazem, Mohammad; Vosough, Ahmad; Mohitmafi, Soroush; Najarasl, Mostafa; Ajdari, Zahra; Yazdi, Reza Salman; Bagheri, Mohsen; Ghanaati, Hossein; Rafiei, Behrooz; Gheisari, Yousof; Baharvand, Hossein; Aghdami, Nasser

2014-06-01

Clinically, acute kidney injury (AKI) is a potentially devastating condition for which no specific therapy improves efficacy of the repair process. Bone marrow mesenchymal stromal cells (BM-MSCs) are proven to be beneficial for the renal repair process after AKI in different experimental rodent models, but their efficacy in large animals and humans remains unknown. This study aims to assess the effect of autologous rhesus Macaque mulatta monkey BM-MSC transplantation in cisplatin-induced AKI. We chose a model of AKI induced by intravenous administration of 5 mg/kg cisplatin. BM-MSCs were transplanted through intra-arterial injection. The animals were followed for survival, biochemistry analysis and pathology. Transplantation of 5 × 10(6) cells/kg ameliorated renal function during the first week, as shown by significantly lower serum creatinine and urea values and higher urine creatinine and urea clearance without hyponatremia, hyperkalemia, proteinuria and polyuria up to 84 d compared with the vehicle and control groups. The superparamagnetic iron oxide nanoparticle-labeled cells were found in both the glomeruli and tubules. BM-MSCs markedly accelerated Foxp3+ T-regulatory cells in response to cisplatin-induced damage, as revealed by higher numbers of Foxp3+ cells within the tubuli of these monkeys compared with cisplatin-treated monkeys in the control and vehicle groups. These data demonstrate that BM-MSCs in this unique large-animal model of cisplatin-induced AKI exhibited recovery and protective properties. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice.

PubMed

Ezquer, Fernando E; Ezquer, Marcelo E; Parrau, Daniela B; Carpio, Daniel; Yañez, Alejandro J; Conget, Paulette A

2008-06-01

Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 diabetes C57BL/6 mice, we tested whether a single intravenous dose of MSCs led to recovery of pancreatic and renal function and structure. When hyperglycemia, glycosuria, massive beta-pancreatic islets destruction, and mild albuminuria were evident (but still without renal histopathologic changes), mice were randomly separated in 2 groups: 1 received 0.5 x 10(6) MSCs that have been ex vivo expanded (and characterized according to their mesenchymal differentiation potential), and the other group received the vehicle. Within a week, only MSC-treated diabetic mice exhibited significant reduction in their blood glucose levels, reaching nearly euglycemic values a month later. Reversion of hyperglycemia and glycosuria remained for 2 months at least. An increase in morphologically normal beta-pancreatic islets was observed only in MSC-treated diabetic mice. Furthermore, in those animals albuminuria was reduced and glomeruli were histologically normal. On the other side, untreated diabetic mice presented glomerular hyalinosis and mesangial expansion. Thus, MSC administration resulted in beta-pancreatic islets regeneration and prevented renal damage in diabetic animals. Our preclinical results suggest bone marrow-derived MSC transplantation as a cell therapy strategy to treat type 1 diabetes and prevent diabetic nephropathy, its main complication.

Pharmacokinetics of Genetically Engineered Antibody Forms Using Positron Emission Tomography

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

Cheung, Nai-Kong V.; Modak, Shakeel; Lin, Yukang

2004-08-31

In the last grant period we have focused on multi-step targeting methodologies (MST), as a method for delivery of high dose to the tumor, with low dose to the bone marrow. We have explored uptake in colorectal, pancreatic and prostate cancer, using an special preparation, developed in collaboration with NeoRex A high tumor/bone marrow ratio is clearly achieved with MST, but with a cost, namely the higher dose to normal kidney. For this reason, we have in particular, (a) looked dosimetry for both tumor and normal organ, and especially renal dosimetry, which appears to be the target organ, for Y-90.more » (b) In parallel with this we have explored the dosimetry of very high dose rate radionuclides, including Holmium-166. (c) In addition, with NaiKong Cheung, we have developed a new MST construct based on the anti-GD2 targeting 5F11; (d) we have successfully completed development of s-factor tables for mice. In summary, renal dosimetry is dominated by about 4-5% of the injected dose being held long-term in the renal cortex, probably in the proximal tubule, due to the universal uptake of small proteins. This appears to be a function of a biotynlated protein binding of the strept-avidin construct, to HSP70. This cortical uptake has caused us to reconsider renal dosimetry as a whole, with the smaller mass of the cortex, rather than the whole kidney, as the target organ. These insights into dosimetry will be of great importance as MST, becomes more common in clinical practice.« less

The construction of a panel of serum amino acids for the identification of early chronic kidney disease patients.

PubMed

Li, Rui; Dai, Jinna; Kang, Hui

2018-03-01

Serum creatinine, urea, and cystatin-c are standardly used for the evaluation of renal function in the clinic. However, some patients have chronic kidney disease but still retain kidney function; a conventional serum index in these patients can be completely normal. Serum amino acid levels can reflect subtle changes in metabolism and are closely related to renal function. Here, we investigated how amino acids change as renal impairment increases. Subjects were divided into three groups by renal function glomerular filtration rate: healthy controls, patients with chronic kidney disease with normal kidney function, and patients with chronic kidney disease with decreased kidney function group. We identified 11 amino acids of interest using LC-MS/MS on MRM (+) mode. Statistical analysis indicated that alanine (ALA), valine (VAL), and tyrosine (TYR) decrease with renal function impairment, whereas phenylalanine (PHE) and citrulline (CIT) increase. We tried to construct a diagnostic model utilizing a combination of amino acids capable of identifying early chronic kidney disease patients. The accuracy, specificity, and sensitivity of the combining predictors were 86.9%, 84.6%, and 90.9%, respectively, which is superior to the reported values for serum creatinine, urea, and cystatin-c. Our data suggest that serum amino acid levels may supply important information for the early detection of chronic kidney disease. We are the first to establish a diagnostic model utilizing serum levels of multiple amino acids for the diagnosis of patients with early-stage chronic kidney disease. © 2017 Wiley Periodicals, Inc.

Radiology of sarcoidosis.

PubMed

James, D G; Timmis, B; Barter, S; Carstairs, S

1989-03-01

This review of the radiology of sarcoidosis encompasses intrathoracic involvement, upper respiratory tract sarcoidosis, pleural disease, and involvement of bone, joint, neurological system, heart, kidney and alimentary tract. Attention is drawn to the value of CT scans, magnetic resonance imaging, gallium, and neutron activation analysis.

Electrophoresis of biological materials

NASA Technical Reports Server (NTRS)

1975-01-01

The selection of biological products was studied for electrophoresis in space. Free flow electrophoresis, isoelectric focusing, and isotachophoresis are described. The candidates discussed include: immunoglobulins and gamma globulins; isolated islet of langerhans from pancreas; bone marrow; tumor cells; kidney cells, cryoprecipitate; and column separated cultures.

DEVELOPING COMPLETE ULTRASONIC MANAGEMENT OF KIDNEY STONES FOR SPACEFLIGHT.

PubMed

Simon, Julianna C; Dunmire, Barbrina; Bailey, Michael R; Sorensen, Mathew D

2016-09-01

Bone demineralization, dehydration, and stasis put astronauts at an increased risk of forming kidney stones in space. The incidence of kidney stones and the potential for a mission-critical event are expected to rise as expeditions become longer and immediate transport to Earth becomes more problematic. At the University of Washington, we are developing an ultrasound-based stone management system to detect stones with S-mode ™ ultrasound imaging, break stones with burst wave lithotripsy (BWL ™ ), and reposition stones with ultrasonic propulsion (UP ™ ) on Earth and in space. This review discusses the development and current state of these technologies, as well as integration on the flexible ultrasound system sponsored by NASA and the National Space Biomedical Research Institute.

Association of pulse wave velocity and pulse pressure with decline in kidney function.

PubMed

Kim, Chang Seong; Kim, Ha Yeon; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2014-05-01

The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) ). ©2014 Wiley Periodicals, Inc.

Calcium and Bone Metabolism Indices.

PubMed

Song, Lu

2017-01-01

Calcium and inorganic phosphate are of critical importance for many body functions, thus the regulations of their plasma concentrations are tightly controlled by the concerted actions of reabsorption/excretion in the kidney, absorption in the intestines, and exchange from bone, the major reservoir for calcium and phosphate in the body. Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) control calcium homeostasis, whereas PTH, 1,25(OH) 2 D, and bone-derived fibroblast growth factor 23 (FGF 23) control phosphate homeostasis. Hypoparathyroidism can cause hypocalcemia and hyperphosphatemia, whereas deficient vitamin D actions can cause osteomalacia in adults and rickets in children. Hyperparathyroidism, alternatively, can cause hypercalcemia and hypophosphatemia. Laboratory tests of calcium, phosphate, PTH, and 25-hydroxyvitamin D are very useful in the diagnosis of abnormalities associated with calcium and/or phosphate metabolisms. Bone is constantly remodeled throughout life in response to mechanical stress and a need for calcium in extracellular fluids. Metabolic bone diseases such as osteoporosis, osteomalacia in adults or rickets in children, and renal osteodystrophy develop when bone resorption exceeds bone formation. Bone turnover markers (BTM) such as serum N-terminal propeptide of type I procollagen (P1NP) and C-terminal collagen cross-link (CTX) may be useful in predicting future fracture risk or monitoring the response to anti-resorptive therapy. There is a need to standardize sample collection protocols because certain BTMs exhibit large circadian variations and tend to be influenced by food intakes. In the United States, a project to standardize BTM sample collection protocols and to establish the reference intervals for serum P1NP and serum CTX is ongoing. We anticipate the outcome of this project to shine lights on the standardization of BTM assays, sample collection protocols, reference intervals in relation to age, sex, and ethnic origins, and clinical utilities of BTMs. This review will briefly discuss the regulations of calcium and phosphate homeostasis, laboratory's role in the diagnosis, and monitoring of bone and calcium metabolism, as well as the usefulness and controversies of the utilities of BTMs in the diagnosis and monitoring of metabolic bone diseases. © 2017 Elsevier Inc. All rights reserved.

Thyroid function, reduced kidney function and incident chronic kidney disease in a community-based population: the Atherosclerosis Risk in Communities study.

PubMed

Schultheiss, Ulla T; Daya, Natalie; Grams, Morgan E; Seufert, Jochen; Steffes, Michael; Coresh, Josef; Selvin, Elizabeth; Köttgen, Anna

2017-11-01

Reduced kidney function is a common public health problem that increases risk for a wide variety of adverse outcomes, making the identification of potentially modifiable factors associated with the development of incident chronic kidney disease (CKD) important. Alterations in the hypothalamic-pituitary-thyroid axis have been linked to reduced kidney function, but the association of thyroid function with the development of incident CKD is largely uncharacterized. Concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3) and thyroid peroxidase antibody (TPOAb) were quantified in 12 785 black and white participants of the ongoing community-based prospective Atherosclerosis Risk in Communities study. Thyroid markers and clinical categories of thyroid dysfunction (euthyroidism, combined subclinical and overt hypothyroidism, combined subclinical and overt hyperthyroidism) were also evaluated for their association with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2) at study baseline and with incident CKD over a median follow-up time of 19.6 years. Higher TSH and FT4 as well as lower T3 concentrations were strongly and independently associated with reduced kidney function at study baseline. The clinical entities hypothyroidism and hyperthyroidism were also associated with higher odds of baseline reduced kidney function, but this was not significant. However, none of the markers of thyroid function nor different clinical categories of thyroid dysfunction (hypothyroidism, hyperthyroidism or TPOAb positivity) were associated with incident CKD in adjusted analyses. Elevated TSH, FT4 and reduced T3 concentrations were associated with reduced kidney function cross-sectionally. The lack of association with the development of incident CKD suggests that altered thyroid function in the general population is not causally related to CKD development, but screening for thyroidal status may be especially relevant in persons with reduced kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Vitamin K status in chronic kidney disease.

PubMed

McCabe, Kristin M; Adams, Michael A; Holden, Rachel M

2013-11-07

The purpose of this review is to summarize the research to date on vitamin K status in chronic kidney disease (CKD). This review includes a summary of the data available on vitamin K status in patients across the spectrum of CKD as well as the link between vitamin K deficiency in CKD and bone dynamics, including mineralization and demineralization, as well as ectopic mineralization. It also describes two current clinical trials that are underway evaluating vitamin K treatment in CKD patients. These data may inform future clinical practice in this population.

Cystatin C is Better than Serum Creatinine for Estimating Glomerular Filtration Rate to Detect Osteopenia in Chronic Kidney Disease Patients.

PubMed

Kwon, Young Eun; Lee, Mi Jung; Park, Kyoung Sook; Han, Seung Hyeok; Yoo, Tae Hyun; Oh, Kook Hwan; Lee, Joongyub; Lee, Kyu Beck; Chung, Wookyung; Kim, Yeong Hoon; Ahn, Curie; Choi, Kyu Hun

2017-03-01

Recent studies have reported that loss of bone mass is associated with renal function decline and increased fracture risks in chronic kidney disease (CKD) patients. The aim of this study was to investigate the best estimated glomerular filtration rate (eGFR) equation to detect osteopenia in CKD patients. This was a cross-sectional study, and 780 patients aged 50 years or above were classified into normal bone mass or osteopenia groups according to the -1.0 of T-scores at total hip and femur neck. Comparisons of area under the receiver operating characteristic (ROC) curves (AUC) were performed to investigate significant differences among three eGFR formulas: Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration (EPI) creatinine, and CKD-EPI cystatin C (CKD-EPI-Cys). The mean age was 61 years old and the proportion of females was 37.3%. The total hip osteopenia group showed lower CKD-EPI-Cys eGFR levels (osteopenia group, 33.3±19.0 mL/min/1.73 m²; normal group, 48.1±26.2 mL/min/1.73 m², p<0.001). In multiple logistic regression analysis, CKD-EPI-Cys eGFR was independently associated with osteopenia at the total hip (per 1 mL/min/1.73 m² increase, odds ratio 0.98, 95% confidence interval 0.97-0.99, p=0.004) after adjusting for confounding variables. ROC curve analyses indicated that CKD-EPI-Cys shows the largest AUC for osteopenia at the total hip (AUC=0.678, all p<0.01) and the femur neck (AUC=0.665, all p<0.05). Decreased renal function assessed by CKD-EPI-Cys equation correlates with osteopenia better than creatinine-based methods in CKD patients, and the CKD-EPI-Cys formula might be a useful tool to assess skeletal-related event risks.

Facial paralysis caused by metastasis of breast carcinoma to the temporal bone.

PubMed

Lan, Ming-Ying; Shiao, An-Suey; Li, Wing-Yin

2004-11-01

Metastatic tumors to the temporal bone are very rare. The most common sites of origin of temporal bone metastases are breast, lung, kidney, gastrointestinal tract, larynx, prostate gland, and thyroid gland. The pathogenesis of spread to the temporal bone is most commonly by the hematogenous route. The common otologic symptoms that manifest with facial nerve paralysis are often thought to be due to a mastoid infection. Here is a report on a case of breast carcinoma presenting with otalgia, otorrhea, and facial paralysis for 2 months. The patient was initially diagnosed as mastoiditis, and later the clinical impression was revised to metastatic breast carcinoma to temporal bone, based on the pathologic findings. Metastatic disease should be considered as a possible etiology in patients with a clinical history of malignant neoplasms presenting with common otologic or vestibular symptoms, especially with facial nerve paralysis.

The role of erythropoiesis stimulating agents and intravenous (IV) iron in the cardio renal anemia syndrome.

PubMed

Silverberg, Donald S

2011-11-01

Anemia is common in Congestive Heart Failure (CHF) and is associated with an increased mortality, morbidity and progressive renal failure. The most common causes of the anemia in CHF are (1) the associated Chronic Kidney Disease (CKD), which causes depression of erythropoietin (EPO) production in the kidney, and (2) excessive cytokine production in CHF, which can cause both depression of erythropoietin production in the kidney and depression of erythropoietin response in the bone marrow. The cytokines can also induce iron deficiency by increasing hepcidin production from the liver, which both reduces gastrointestinal iron absorption and reduces iron release from iron stores located in the macrophages and hepatocytes. It appears that iron deficiency is very common in CHF and is rarely recognized or treated. The iron deficiency can cause a thrombocytosis that might contribute to cardiovascular complications in both CHF and CKD and is reversible with iron treatment. Thus, attempts to control this anemia in CHF will have to take into consideration both the use of both Erythropoiesis Stimulating Agents (ESA) such as EPO and oral and, probably more importantly, intravenous (IV) iron. Many studies of anemia in CHF with ESA and oral or IV iron and even with IV iron without ESA have shown a positive effect on hospitalization, New York Heart Association functional class, cardiac and renal function, quality of life, exercise capacity and reduced Beta Natriuretic Peptide and have not demonstrated an increase in cardiovascular damage related to the therapy. However, adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are still needed and are currently being carried out.

Milan hypertensive rat as a model for studying cation transport abnormality in genetic hypertension

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

Ferrari, P.; Barber, B.R.; Torielli, L.

1987-11-01

Environmental factors, genetic polymorphisms, and different experimental designs have been the main impediments to evaluating a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. We review the results obtained in the Milan hypertensive strain of rats (MHS) and in its appropriate control normotensive strain (MNS) to illustrate our approach to defining the role of cation transport abnormality in a type of genetic hypertension. Before the development of a difference in blood pressure between the two strains, the comparison of kidney and erythrocyte functions showed that MHS had an increased glomerular filtration rate and urinarymore » output, and lower plasma renin and urine osmolality. Kidney cross-transplantation between the strains showed that hypertension is transplanted with the kidney. Proximal tubular cell volume and sodium content were lower in MHS while sodium transport across the brush border membrane vesicles of MHS was faster. Erythrocytes in MHS were smaller and had lower sodium concentration, and Na+-K+ cotransport and passive permeability were faster. The differences in volume, sodium content, and Na+-K+ cotransport between erythrocytes of the two strains persisted after transplantation of bone marrow to irradiated F1 (MHS X MNS) hybrids. Moreover, in normal segregating F2 hybrid populations there was a positive correlation between blood pressure and Na+-K+ cotransport. These results suggest a genetic and functional link in MHS between cell membrane cation transport abnormalities and hypertension. Thus, erythrocyte cell membrane may be used for approaching the problem of defining the genetically determined molecular mechanism underlying the development of a type of essential hypertension. 35 references.« less

[Banff score changes in kidneys from marginal donors].

PubMed

Borda, Bernadett; Szederkényi, Edit; Ottlakán, Aurél; Kemény, Éva; Szabó, Viktor; Hódi, Zoltán; Lázár, György

2016-02-21

Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation. Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys. Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation. Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients.

Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

PubMed

Mazidi, Moshen; Rezaie, Peyman; Covic, Adriac; Malyszko, Jolanta; Rysz, Jacek; Kengne, Andre Pascal; Banach, Maciej

2017-10-06

Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p <0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, p =0.056). The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits.

PubMed

Kozlowski, Piotr; Montgomery, Scott; Befekadu, Rahel; Hahn-Strömberg, Victoria

2017-01-01

Light chain amyloidosis (AL) is a rare deposition disease and is present in 10-15% of patients with myeloma (MM). In contrast to symptomatic AL in MM, presence of bone marrow (BM) amyloid deposits (AD) in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM). We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM)/lambda MM with and without BM-AD. Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively) and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively). Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively). Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD.

What Is Atherosclerosis?

MedlinePlus

... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

(Re)Building a Kidney

PubMed Central

Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

2017-01-01

(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys

NASA Technical Reports Server (NTRS)

Sakhaee, K.; Wabner, C. L.; Zerwekh, J. E.; Copley, J. B.; Pak, L.; Poindexter, J. R.; Pak, C. Y.

1993-01-01

It has been suggested that calcium citrate might enhance aluminum absorption from food, posing a threat of aluminum toxicity even in patients with normal renal function. We therefore measured serum and urinary aluminum before and following calcium citrate therapy in patients with moderate renal failure and in normal subjects maintained on constant metabolic diets with known aluminum content (967-1034 mumol/day, or 26.1-27.9 mg/day, in patients and either 834 or 1579 mumol/day, or 22.5 and 42.6 mg/day, in normal subjects). Seven patients with moderate renal failure (endogenous creatinine clearance of 43 ml/min) took 50 mmol (2 g) calcium/day as effervescent calcium citrate with meals for 17 days. Eight normal women received 25 mmol (1 g) calcium/day as tricalcium dicitrate tablets with meals for 7 days. In patients with moderate renal failure, serum and urinary aluminum were normal before treatment at 489 +/- 293 SD nmol/l (13.2 +/- 7.9 micrograms/l) and 767 +/- 497 nmol/day (20.7 +/- 13.4 micrograms/day), respectively. They remained within normal limits and did not change significantly during calcium citrate treatment (400 +/- 148 nmol/l and 600 +/- 441 nmol/day, respectively). Similarly, no significant change in serum and urinary aluminum was detected in normal women during calcium citrate administration (271 +/- 59 vs 293 +/- 85 nmol/l and 515 +/- 138 vs 615 +/- 170 nmol/day, respectively). In addition, skeletal bone aluminum content did not change significantly in 14 osteoporotic patients (endogenous creatinine clearance of 68.5 ml/min) treated for 24 months with calcium citrate, 10 mmol calcium twice/day separately from meals (29.3 +/- 13.9 ng/mg ash bone to 27.9 +/0- 10.4, P = 0.727). In them, histomorphometric examination did not show any evidence of mineralization defect. Thus, calcium citrate given alone without aluminum-containing drugs does not pose a risk of aluminum toxicity in subjects with normal or functioning kidneys, when it is administered on an empty stomach at a recommended dose of 20 mmol calcium/day.

Fibroblast Growth Factor-23 in Bed Rest and Spaceflight

NASA Technical Reports Server (NTRS)

Bokhari, R.; Zwart, S. R; Fields, E.; Heer, M.; Sibonga, J.; Smith, S. M.

2014-01-01

Many nutritional factors influence bone, from the basics of calcium and vitamin D, to factors which influence bone through acid/base balance, including protein, sodium, and more. Fibroblast growth factor 23 (FGF23) is a recently identified factor, secreted from osteocytes, which is involved in classic (albeit complex) feedback loops controlling phosphorus homeostasis through both vitamin D and parathyroid hormone (PTH) (1, 2). As osteocytes are gravity sensing cells, it is important to determine if there are changes in FGF23 during spaceflight. In extreme cases, such as chronic kidney disease, FGF23 levels are highly elevated. FGF23 imbalances, secondary to dietary influences, may contribute to skeletal demineralization and kidney stone risk during spaceflight. Presented with an imbalanced dietary phosphorus to calcium ratio, increased secretion of FGF23 will inhibit renal phosphorus reabsorption, resulting in increased excretion and reduced circulating phosphorus. Increased intake and excretion of phosphorus is associated with increased kidney stone risk in both the terrestrial and microgravity environments. Highly processed foods and carbonated beverages are associated with higher phosphorus content. Ideally, the dietary calcium to phosphorus ratio should be at minimum 1:1. Nutritional requirements for spaceflight suggest that this ratio not be less than 0.67 (3), while the International Space Station (ISS) menu provides 1020 mg Ca and 1856 mg P, for a ratio of 0.55 (3). Subjects in NASA's bed rest studies, by design, have consumed intake ratios much closer to 1.0 (4). FGF23 also has an inhibitory influence on PTH secretion and 1(alpha)-hydroxylase, both of which are required for activating vitamin D with the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Decreased 1,25-dihydroxyvitamin D will result in decreased intestinal phosphorus absorption, and increased urinary phosphorus excretion (via decreased renal reabsorption). Should a decrease in 1,25- dihydroxyvitamin D be necessary to reduce intestinal phosphorus absorption, calcium absorption will also proportionally be reduced, potentially leading to skeletal demineralization. Demineralization of bone can increase kidney stone risk, a medical issue that could prove detrimental to mission success. Given the interrelationships described above, we sought to determine circulating FGF23 concentrations in spaceflight and ground analog studies to better understand the potential effects of dietary phosphorus on bone and calcium metabolism. We analyzed serum from ISS astronauts participating in studies of bone biochemistry, including the Nutrition SMO and Pro K experiments, and we also evaluated FGF23 during extended-duration bed rest. Serum intact FGF23 levels were determined using an ELISA kit from Kainos laboratories in Japan. While initial evaluation of the data showed no changes over time during flight or bed rest, evaluation continues of FGF23 data in light of dietary factors, PTH, vitamin D status, and other biochemical and endocrine factors.

Space research on organs and tissues

NASA Technical Reports Server (NTRS)

Tischler, Marc E.; Morey-Holton, Emily

1993-01-01

Studies in space on various physiological systems have and will continue to provide valuable information on how they adapt to reduced gravitational conditions, and how living in a 1 g (gravity) environment has guided their development. Muscle and bone are the most notable tissues that respond to unweighting caused by lack of gravity. The function of specific muscles and bones relates directly to mechanical loading, so that removal of 'normal forces' in space, or in bedridden patients, causes dramatic loss of tissue mass. The cardiovascular system is also markedly affected by reduced gravity. Adaptation includes decreased blood flow to the lower extremities, thus decreasing the heart output requirement. Return to 1 g is associated with a period of reconditioning due to the deconditioning that occurs in space. Changes in the cardiovascular system are also related to responses of the kidney and certain endocrine (hormone-producing) organs. Changes in respiratory function may also occur, suggesting an effect on the lungs, though this adaptation is poorly understood. The neurovestibular system, including the brain and organs of the inner ear, must adapt to the disorientation caused by lack of gravity. Preliminary findings have been reported for liver. Additionally, endocrine organs responsible for release of hormones such as insulin, growth hormone, glucocorticoids, and thyroid hormone may respond to spaceflight.

MRI tools for assessment of microstructure and nephron function of the kidney.

PubMed

Xie, Luke; Bennett, Kevin M; Liu, Chunlei; Johnson, G Allan; Zhang, Jeff Lei; Lee, Vivian S

2016-12-01

MRI can provide excellent detail of renal structure and function. Recently, novel MR contrast mechanisms and imaging tools have been developed to evaluate microscopic kidney structures including the tubules and glomeruli. Quantitative MRI can assess local tubular function and is able to determine the concentrating mechanism of the kidney noninvasively in real time. Measuring single nephron function is now a near possibility. In parallel to advancing imaging techniques for kidney microstructure is a need to carefully understand the relationship between the local source of MRI contrast and the underlying physiological change. The development of these imaging markers can impact the accurate diagnosis and treatment of kidney disease. This study reviews the novel tools to examine kidney microstructure and local function and demonstrates the application of these methods in renal pathophysiology. Copyright © 2016 the American Physiological Society.

Kidney Involvement of Patients with Waldenström Macroglobulinemia and Other IgM-Producing B Cell Lymphoproliferative Disorders.

PubMed

Higgins, Larissa; Nasr, Samih H; Said, Samar M; Kapoor, Prashant; Dingli, David; King, Rebecca L; Rajkumar, S Vincent; Kyle, Robert A; Kourelis, Taxiarchis; Gertz, Morie A; Dispenzieri, Angela; Lacy, Martha Q; Buadi, Francis K; Ansell, Stephen M; Gonsalves, Wilson I; Thompson, Carrie A; Fervenza, Fernando C; Zand, Ladan; Hwa, Yi L; Jevremovic, Dragan; Shi, Min; Leung, Nelson

2018-05-30

Kidney involvement in Waldenström macroglobulinemia is less well described compared with kidney manifestations in multiple myeloma. Of the 1363 patients seen with Waldenström macroglobulinemia and other IgM-secreting B cell lymphoproliferative disorders seen at the Mayo Clinic between 1996 and 2015, 57 kidney biopsies were retrospectively studied. The biopsy findings were correlated with clinical, kidney, and hematologic characteristics. Criteria for inclusion were evidence of a monoclonal IgM protein and availability of a kidney and a bone marrow biopsy for review. Glomerular and tubulointerstitial pathologies were categorized according to whether they were related to the monoclonal IgM. Of the 57 patients identified, monoclonal gammopathy-related kidney lesions were identified in 82% (47 of 57 biopsies), whereas nonmonoclonal gammopathy-related kidney lesions were seen in 18% (ten of 57). Monoclonal gammopathy-related kidney lesions included monoclonal Ig-related amyloidosis ( n =19; 33%), nonamyloid glomerulopathy ( n =20, 35%), and tubulointerstitial nephropathies ( n =8; 14%). The most common monoclonal gammopathy-related kidney lesion was monoclonal Ig-related amyloidosis ( n =19; 33%) followed by cryoglobulinemic GN ( n =13; 28%). Lymphoma infiltration was the most common tubulointerstitial lesion ( n =4; 9%). The hematologic diagnosis was Waldenström macroglobulinemia in 74% ( n =42), monoclonal gammopathy of renal significance in 16% ( n =9), and marginal zone lymphoma ( n =2), chronic lymphocytic leukemia ( n =2), and low-grade B cell lymphoma ( n =2) in 4% each. Our study confirms a diverse variety of kidney lesions in patients with monoclonal IgM gammopathy. Copyright © 2018 by the American Society of Nephrology.

Adaptive functional change of the contralateral kidney after partial nephrectomy.

PubMed

Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2017-08-01

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.

Periodontitis associated with chronic kidney disease among Mexican Americans.

PubMed

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2013-01-01

In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean. This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. © 2012 American Association of Public Health Dentistry.

Periodontitis associated with Chronic Kidney Disease among Mexican Americans

PubMed Central

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2012-01-01

Objective In comparison to non-Hispanic whites, a number of healthcare disparities, including poor oral health, have been identified among Hispanics in general and Mexican-Americans in particular. We hypothesized that Mexican-Americans with Chronic Kidney disease (CKD) would have higher prevalence of chronic periodontitis compared to Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. Method We examined this hypothesis using the National Health and Nutrition Examination Survey 1988–1994 (NHANES III) dataset. We followed the American Academy of Periodontology (AAP)/Center for Disease Control and Prevention (CDC) case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology (EPI) equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Results Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (p<0.001). Mexican Americans with reduced kidney function were 2-fold more likely to have periodontitis compared to Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes and socioeconomic status. Multivariate adjusted Odds Ratio for periodontitis significantly increased with 1, 5 and 10 mL/minute eGFR reduction from the mean. Conclusion This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. PMID:22775287

Proton Pump Inhibitors and Kidney Disease - GI Upset for the Nephrologist?

PubMed

Toth-Manikowski, Stephanie; Grams, Morgan E

2017-05-01

Widely regarded as safe and effective, proton pump inhibitors (PPIs) are among the most commonly used medications in the world today. However, a spate of observational studies suggest an association between PPI use and adverse events, including infection, bone fracture, and dementia. This review details evidence linking the use of PPI therapy to the development of kidney disease, including early case reports of acute interstitial nephritis and subsequent large observational studies of acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). The majority of studies showed higher risk of kidney outcomes among persons prescribed PPI medications, with effect sizes that were slightly higher for AKI (∼2-3-fold) compared to CKD and ESRD (1.2-1.8-fold). Although observational pharmaco-epidemiology studies are limited by the possibility of residual confounding and confounding by indication, many of the described studies conducted rigorous sensitivity analyses aimed at minimizing these biases, including new-user design, comparison to similar agents (e.g., histamine 2 receptor antagonists), and evaluation for a dose-response, with robust results. Given the widespread use of PPIs, even a small effect on kidney outcomes could result in large public health burden. Timely cessation of PPI therapy when there is no clear indication for use might reduce the population burden of kidney disease.

Is Kidney Transplantation a Better State of CKD? Impact on Diagnosis and Management.

PubMed

Parajuli, Sandesh; Clark, Dana F; Djamali, Arjang

2016-09-01

Patients with CKD are at increased risk for cardiovascular events, hospitalizations, and mortality. Kidney transplantation (KTx) is the preferred treatment for end-stage kidney disease. Although comorbidities including anemia and bone and mineral disease improve or are even halted after KTx, kidney transplant recipients carry higher cardiovascular mortality risk than the general population, as well as an increased risk of infections, malignancies, fractures, and obesity. When comparing CKD with CKD after transplantation (CKD-T), the rate of decline of estimated glomerular filtration rate (eGFR) is significantly lower in CKD-T. Higher rate of decline of eGFR has been associated with increased risk of mortality. However, due to the significant increased risk of mortality due to cardiovascular events, infections, and malignancies, many kidney transplant recipients may not benefit of decline in the rate of eGFR. Patients with CKD-T are a unique subset of patients with multiple traditional and transplant-specific risk factors. Proper management and appropriate preventive health measures may improve long-term patient and allograft survival in patients with CKD-T. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Elevated Vitamin D Receptor Levels in Genetic Hypercalciuric Stone-Forming Rats Are Associated With Downregulation of Snail

PubMed Central

Bai, Shaochun; Wang, Hongwei; Shen, Jikun; Zhou, Randal; Bushinsky, David A; Favus, Murray J

2010-01-01

Patients with idiopathic hypercalciuria (IH) and genetic hypercalciuric stone-forming (GHS) rats, an animal model of IH, are both characterized by normal serum Ca, hypercalciuria, Ca nephrolithiasis, reduced renal Ca reabsorption, and increased bone resorption. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels are elevated or normal in IH and are normal in GHS rats. In GHS rats, vitamin D receptor (VDR) protein levels are elevated in intestinal, kidney, and bone cells, and in IH, peripheral blood monocyte VDR levels are high. The high VDR is thought to amplify the target-tissue actions of normal circulating 1,25(OH)2D levels to increase Ca transport. The aim of this study was to elucidate the molecular mechanisms whereby Snail may contribute to the high VDR levels in GHS rats. In the study, Snail gene expression and protein levels were lower in GHS rat tissues and inversely correlated with VDR gene expression and protein levels in intestine and kidney cells. In human kidney and colon cell lines, ChIP assays revealed endogenous Snail binding close to specific E-box sequences within the human VDR promoter region, whereas only one E-box specifically bound Snail in the rat promoter. Snail binding to rat VDR promoter E-box regions was reduced in GHS compared with normal control intestine and was accompanied by hyperacetylation of histone H3. These results provide evidence that elevated VDR in GHS rats likely occurs because of derepression resulting from reduced Snail binding to the VDR promoter and hyperacetylation of histone H3. © 2010 American Society for Bone and Mineral Research. PMID:19929616

Molecular modifiers reveal a mechanism of pathological crystal growth inhibition

NASA Astrophysics Data System (ADS)

Chung, Jihae; Granja, Ignacio; Taylor, Michael G.; Mpourmpakis, Giannis; Asplin, John R.; Rimer, Jeffrey D.

2016-08-01

Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization—citrate and hydroxycitrate—exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of calcium oxalate monohydrate nucleation as is citrate. Our findings support exploration of the clinical potential of hydroxycitrate as an alternative treatment to citrate for kidney stones.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Body distribution of trace elements in black-tailed gulls from Rishiri Island, Japan: age-dependent accumulation and transfer to feathers and eggs.

PubMed

Agusa, Tetsuro; Matsumoto, Taro; Ikemoto, Tokutaka; Anan, Yasumi; Kubota, Reiji; Yasunaga, Genta; Kunito, Takashi; Tanabe, Shinsuke; Ogi, Haruo; Shibata, Yasuyuki

2005-09-01

Body distribution and maternal transfer of 18 trace elements (V, Cr, Mn, Co, Cu, Zn, Se, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, Hg, Tl, and Pb) to eggs were examined in black-tailed gulls (Larus crassirostris), which were culled in Rishiri Island, Hokkaido Prefecture, Japan. Manganese, Cu, Rb, Mo, and Cd showed the highest levels in liver and kidney, Ag, Sb, and Hg in feather, and V, Sr, and Pb in bone. Maternal transfer rates of trace elements ranged from 0.8% (Cd) to as much as 65% (Tl) of maternal body burden. Large amounts of Sr, Ba, and Tl were transferred to the eggs, though maternal transfer rates of V, Cd, Hg, and Pb were substantially low. It also was observed that Rb, Sr, Cd, Cs, and Ba hardly were excreted into feathers. Concentrations of Co in liver, Ba in liver and kidney, and Mo in liver increased significantly with age, whereas Se in bone and kidney, Hg in kidney, and Cr in feather decreased with age in the known-aged black-tailed gulls (2-20 years old). It also was suggested that feathers might be useful to estimate contamination status of trace elements in birds, especially for Hg on a population basis, although the utility is limited on an individual basis for the black-tailed gulls. To our knowledge, this is the first report on the maternal transfer rate of multielements and also on the usefulness of feathers to estimate contamination status of Hg in birds on a population basis.

Comparison of the morphometric features of the left and right horse kidneys: a stereological approach.

PubMed

Bolat, D; Bahar, S; Tipirdamaz, S; Selcuk, M L

2013-12-01

The aims of this study were to determine the total volume of the horse kidney and volume fractions of its functional subcomponents (cortex, medulla, renal pelvis) using stereological methods and investigate any possible difference in the functional subcomponents of the right and left kidneys that may arise from differences in shape. The study was carried out on the kidneys of 5 horses of different breed and sex. The weight of the kidneys was measured by a digital scale, and kidney volume was calculated by Archimedes' principle. Total kidney volume and volume fractions of subcomponents of the right and left kidneys were estimated by the Cavalieri's principle. The weights of the right and left kidneys were 550 ± 25 g and 585 ± 23 g, respectively. The volumes of the right and left kidneys estimated using the Cavalieri method were 542 ± 46 ml and 581 ± 29 ml. The relative organ weight of the kidneys was calculated as 1:330. The densities of the right and left kidneys were determined to be 1.01 and 1.00, respectively. The mean volume fractions of the cortex, medulla and renal pelvis were determined as 55.6, 42.7 and 1.7 in both kidneys. No statistically significant difference existed between morphometric data pertaining to the right and left kidneys (P > 0.05). To determine precisely whether differences in shape cause any difference in the functional subcomponents of the right and left kidneys requires further investigation of differences in the number of microscopically functional unit of the kidney such as renal glomeruli and nephrons. © 2013 Blackwell Verlag GmbH.

Effect of Carbon Dioxide on the Twinkling Artifact in Ultrasound Imaging of Kidney Stones: A Pilot Study.

PubMed

Simon, Julianna C; Wang, Yak-Nam; Cunitz, Bryan W; Thiel, Jeffrey; Starr, Frank; Liu, Ziyue; Bailey, Michael R

2017-05-01

Bone demineralization, dehydration and stasis put astronauts at increased risk of forming kidney stones in space. The color-Doppler ultrasound "twinkling artifact," which highlights kidney stones with color, can make stones readily detectable with ultrasound; however, our previous results suggest twinkling is caused by microbubbles on the stone surface which could be affected by the elevated levels of carbon dioxide found on space vehicles. Four pigs were implanted with kidney stones and imaged with ultrasound while the anesthetic carrier gas oscillated between oxygen and air containing 0.8% carbon dioxide. On exposure of the pigs to 0.8% carbon dioxide, twinkling was significantly reduced after 9-25 min and recovered when the carrier gas returned to oxygen. These trends repeated when pigs were again exposed to 0.8% carbon dioxide followed by oxygen. The reduction of twinkling caused by exposure to elevated carbon dioxide may make kidney stone detection with twinkling difficult in current space vehicles. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Influence of thyroid function on glomerular filtration rate and other estimates of kidney function in two pediatric patients.

PubMed

Uemura, Osamu; Iwata, Naoyuki; Nagai, Takuhito; Yamakawa, Satoshi; Hibino, Satoshi; Yamamoto, Masaki; Nakano, Masaru; Tanaka, Kazuki

2018-05-01

To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or β2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or β2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.

Nutritional concerns in osteoporosis

USDA-ARS?s Scientific Manuscript database

Key Points: - Adequate calcium intake, 1,000-1,200 mg per day, supports the preservation of bone mass in older adults. - Higher calcium intake should be avoided because it adds no value and may increase the risk of kidney stones and higher cardiovascular disease, although the evidence is inconsiste...

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2014-05-01

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

Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Hsu, Raymond K; Chai, Boyang; Roy, Jason A; Anderson, Amanda H; Bansal, Nisha; Feldman, Harold I; Go, Alan S; He, Jiang; Horwitz, Edward J; Kusek, John W; Lash, James P; Ojo, Akinlolu; Sondheimer, James H; Townsend, Raymond R; Zhan, Min; Hsu, Chi-Yuan

2016-08-01

It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. Prospective cohort study. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point. All-cause mortality within 1 year after initiating hemodialysis therapy. Multivariable Cox proportional hazards. Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

Symptomatic BK Virus Infection Is Associated with Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

PubMed Central

Abudayyeh, Ala; Hamdi, Amir; Lin, Heather; Abdelrahim, Maen; Rondon, Gabriela; Andersson, Borje S; Afrough, Aimaz; Martinez, Charles S; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P.; Marin, David; Gaber, A. Osama; Salahudeen, Abdulla; Oran, Betul; Chemaly, Roy F.; Olson, Amanda; Jones, Roy; Popat, Uday; Champlin, Richard E; Shpall, Elizabeth J.; Winkelmayer, Wolfgang C.; Rezvani, Katayoun

2017-01-01

Nephropathy due to BK virus infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation. We hypothesized that BKV infection was a marker of Kidney Function Decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic hematopoietic stem cell transplantation at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the CKD-EPI equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline and Fine and Gray’s method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic hematopoietic stem cell transplantation, BK viruria was detected in 25% (n=629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease, chronic graft versus host disease, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (P <0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. Post-allogeneic hematopoietic stem cell transplantation, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. PMID:26608093

Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

PubMed

Dong, Jianghu J; Wang, Liangliang; Gill, Jagbir; Cao, Jiguo

2017-01-01

This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.

Effects of feline hyperthyroidism on kidney function: a review.

PubMed

Vaske, Heather H; Schermerhorn, Thomas; Grauer, Gregory F

2016-02-01

Chronic kidney disease and hyperthyroidism are two commonly diagnosed conditions in the geriatric feline population, and are often seen concurrently. Management of both diseases is recommended; however, the physiologic implications of both diseases must be understood to ensure the most favorable outcome for each patient. This report reviews the complex interplay between hyperthyroidism and kidney function, as well as the effects of hyperthyroid therapy on kidney function. © ISFM and AAFP 2015.

Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Chattopadhyay, N.; Kifor, O.; Butters, R. R. Jr; Sugimoto, T.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

1998-01-01

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone remodeling in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to determine whether such osteoblasts express the CaR. In this study, we used the mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells by Northern analysis using a CaR-specific riboprobe and by reverse transcription-polymerase chain reaction with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+), stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken together, our data strongly suggest that the osteoblastic cell line MC3T3-E1 possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a key role in regulating bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local release of Ca2+o.

B-Receptor Signaling in Cardiomyopathy

ClinicalTrials.gov

2015-11-16

Carcinomas; Amyloidosis; Anal Cancer; Anemia; Cholangiocarcinoma of the Extrahepatic Bile Duct; Transitional Cell Carcinoma of Bladder; Bone Marrow Transplant Failure; Bone Cancer; Cancer of Brain and Nervous System; Breast Cancer; Carcinoma of the Large Intestine; Endocrine Cancer; Esophageal Cancer; Eye Cancer; Gall Bladder Cancer; Gastric (Stomach) Cancer; Gastrooesophageal Cancer; Gastrointestinal Stromal Tumor (GIST); Gynecologic Cancers; Head and Neck Cancers; Hepatobiliary Neoplasm; Kidney (Renal Cell) Cancer; Leukemia; Lung Cancer; Hodgkin Disease; Lymphoma, Non-Hodgkin; Mesothelioma; Multiple Myeloma; Myelodysplastic Syndromes (MDS); Neuroendocrine Tumors; Myeloproliferative Disorders; Pancreatic Cancer; Prostate Cancer; Skin Cancer; Soft Tissue Sarcoma; Testicular Cancer; Thymus Cancer; Thyroid Cancer

Aseptic necrosis of the femoral head after pregnancy: a case report.

PubMed

Nassar, Kawtar; Rachidi, Wafae; Janani, Saadia; Mkinsi, Ouafa

2016-01-01

A documented case of beginning aseptic necrosis of the femoral head associated with pregnancy together with a review of the literature about this rare complication of pregnancy is presented. The known risk factors of osteonecrosis are; steroid use, alcoholism, organ transplantation, especially after kidney transplant or bone marrow transplantation bone, systemic lupus erythematosus, dyslipidemia especially hypertriglyceridemia, dysbaric decompression sickness, drepanocytosis and Gaucher's disease. Among the less established factors, we mention procoagulations abnormalities, HIV infection, chemotherapy. We report a case of osteonecrosis of femoral head after pregnancy.

Delayed Graft Function in Living-Donor Kidney Transplant: A Middle Eastern Perspective.

PubMed

Al Otaibi, Torki; Ahmadpoor, Pedram; Allawi, Ali Abdulmajid Dyab; Habhab, Wael Taher; Khatami, Mohammad Reza; Nafar, Mohsen; Glotz, Denis

2016-02-01

With an increased incidence of living-donor kidney transplants, in response to increasing unmet needs for renal transplant, a clear understanding of determinants of posttransplant outcomes is essential. The importance of delayed graft function in deceased-donor kidney transplant is now part of conventional medical wisdom, due to the large amount of evidence focused on this aspect. However, the same is not true for living-donor kidney transplant, partly due to lack of evidence on this crucial clinical question and partly due to lack of awareness about this issue. The current review aims to highlight the importance of delayed graft function as a crucial determinant of outcomes in living-donor kidney transplant. An exhaustive search of online medical databases was performed with appropriate search criteria to collect evidence about delayed graft function after living-donor kidney transplant, with a special focus on studies from the Middle East. Data on incidence, impact, risk factors, and possible prevention modalities of delayed graft function in patients undergoing living-donor kidney transplant are presented. A key finding of this review is that contemporary incidence rates reported from the Middle East are comparatively higher than those reported from outside the region. Although in absolute terms the incidence is lower than deceased donor kidney transplant, the effects of delayed graft function on graft rejection and graft and patient survival are sufficiently large to warrant the formulation of specific treatment protocols. Key to formulating prevention and treatment strategies is identifying discrete risk factors for delayed graft function. Although this evidence is scant, an overview has been provided. Further studies examining different aspects of delayed graft function incidence after living-donor kidney transplant are urgently needed to address a so far little known clinical question.

Influence of low-level laser radiation on kidney functions

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.

1998-12-01

Most of all renal diseases are accompanied by lowering of kidney functions. That makes the quality of the treatment worse. On an example 69 patients receiving Low-Level Laser Therapy (LLLT), the influence of the laser radiation on a contracting system of blood, on current of an active and inactive tubercular inflammation and on partial functions of kidneys were investigated. Is established, that LLLT does not render influence to a contracting system; promotes stopping of unspecific and moderate peaking of a specific inflammation of kidneys. Is proved, that after a rate of laserotherapy the improving of a blood micricirculation in kidney occurs in 57.9% of patients; a secretion - in 63.1% of the patients; a stimulation of urodynamic is fixed in 79% of cases. Magnification of diuresis, improving filtration and concentration functions of kidneys also is marked.

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

PubMed

Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

2011-10-01

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Donation FAQs (Bone and Tissue Allografts)

MedlinePlus

... about organ, tissue and eye donation in your state, visit www.donatelife.net . Is there a difference between tissue and organ donation? In order for a person to become an organ donor (kidney, heart, liver, lung), blood and oxygen must flow through the organs until the time of recovery ...

Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer

ClinicalTrials.gov

2017-03-28

Childhood Choroid Plexus Tumor; Childhood Medulloblastoma; Childhood Pineoblastoma; Childhood Soft Tissue Sarcoma; Childhood Supratentorial Primitive Neuroectodermal Tumor; Neuroblastoma; Osteosarcoma; Retinoblastoma; Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Uranium in bone: metabolic and autoradiographic studies in the rat.

PubMed

Priest, N D; Howells, G R; Green, D; Haines, J W

1982-03-01

The distribution and retention of intravenously injected hexavalent uranium-233 in the skeleton of the female rat has been investigated using a variety of autoradiographic and radiochemical techniques. These showed that approximately one third of the injected uranium is deposited in the skeleton where it is retained with an initial biological half-time of approximately 40 days. The studies also showed that: 1 Uranium is initially deposited onto all types of bone surface, but preferentially onto those that are accreting. 2 Uranium is deposited in the calcifying zones of skeletal cartilage. 3 Bone accretion results in the burial of surface deposits of uranium. 4 Bone resorption causes the removal of uranium from surfaces. 5 Resorbed uranium is not retained by osteoclasts and macrophages in the bone marrow. 6 Uranium removed from bone surfaces enters the bloodstream where most is either redeposited in bone or excreted via the kidneys. 7 The recycling of resorbed uranium within the skeleton tends to produce a uniform level of uranium contamination throughout mineralized bone. These results are taken to indicate that uranium deposition in bone shares characteristics in common with both the 'volume-seeking radionuclides' typified by the alkaline earth elements and with the 'bone surface-seeking radionuclides' typified by plutonium.

In vivo biocompatibility of new nano-calcium-deficient hydroxyapatite/poly-amino acid complex biomaterials.

PubMed

Dai, Zhenyu; Li, Yue; Lu, Weizhong; Jiang, Dianming; Li, Hong; Yan, Yonggang; Lv, Guoyu; Yang, Aiping

2015-01-01

To evaluate the compatibility of novel nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) complex biomaterials with muscle and bone tissue in an in vivo model. Thirty-two New Zealand white rabbits were used in this study. Biomaterials were surgically implanted into each rabbit in the back erector spinae and in tibia with induced defect. Polyethylene was implanted into rabbits in the control group and n-CDHA/PAA into those of the experimental group. Animals were examined at four different points in time: 2 weeks, 4 weeks, 12 weeks, and 24 weeks after surgery. They were euthanized after embolization. Back erector spinae muscles with the surgical implants were examined after hematoxylin and eosin (HE) staining at these points in time. Tibia bones with the surgical implants were examined by X-ray and scanning electron microscopy (SEM) at these points in time to evaluate the interface of the bone with the implanted biomaterials. Bone tissues were sectioned and subjected to HE, Masson, and toluidine blue staining. HE staining of back erector spinae muscles at 4 weeks, 12 weeks, and 24 weeks after implantation of either n-CDHA/PAA or polyethylene showed disappearance of inflammation and normal arrangement in the peripheral tissue of implant biomaterials; no abnormal staining was observed. At 2 weeks after implantation, X-ray imaging of bone tissue samples in both experimental and control groups showed that the peripheral tissues of the implanted biomaterials were continuous and lacked bone osteolysis, absorption, necrosis, or osteomyelitis. The connection between implanted biomaterials and bone tissue was tight. The results of HE, Masson, toluidine blue staining and SEM confirmed that the implanted biomaterials were closely connected to the bone defect and that no rejection had taken place. The n-CDHA/PAA biomaterials induced differentiation of a large number of chondrocytes. New bone trabecula began to form at 4 weeks after implanting n-CDHA/PAA biomaterials, and lamellar bone gradually formed at 12 weeks and 24 weeks after implantation. Routine blood and kidney function tests showed no significant changes at 2 weeks and 24 weeks after implantation of both biomaterials. n-CDHA/PAA composites showed good compatibility in in vivo model. In this study, n-CDHA/PAA were found to be safe, nontoxic, and biologically active in bone repair.

In vivo biocompatibility of new nano-calcium-deficient hydroxyapatite/poly-amino acid complex biomaterials

PubMed Central

Dai, Zhenyu; Li, Yue; Lu, Weizhong; Jiang, Dianming; Li, Hong; Yan, Yonggang; Lv, Guoyu; Yang, Aiping

2015-01-01

Objective To evaluate the compatibility of novel nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) complex biomaterials with muscle and bone tissue in an in vivo model. Methods Thirty-two New Zealand white rabbits were used in this study. Biomaterials were surgically implanted into each rabbit in the back erector spinae and in tibia with induced defect. Polyethylene was implanted into rabbits in the control group and n-CDHA/PAA into those of the experimental group. Animals were examined at four different points in time: 2 weeks, 4 weeks, 12 weeks, and 24 weeks after surgery. They were euthanized after embolization. Back erector spinae muscles with the surgical implants were examined after hematoxylin and eosin (HE) staining at these points in time. Tibia bones with the surgical implants were examined by X-ray and scanning electron microscopy (SEM) at these points in time to evaluate the interface of the bone with the implanted biomaterials. Bone tissues were sectioned and subjected to HE, Masson, and toluidine blue staining. Results HE staining of back erector spinae muscles at 4 weeks, 12 weeks, and 24 weeks after implantation of either n-CDHA/PAA or polyethylene showed disappearance of inflammation and normal arrangement in the peripheral tissue of implant biomaterials; no abnormal staining was observed. At 2 weeks after implantation, X-ray imaging of bone tissue samples in both experimental and control groups showed that the peripheral tissues of the implanted biomaterials were continuous and lacked bone osteolysis, absorption, necrosis, or osteomyelitis. The connection between implanted biomaterials and bone tissue was tight. The results of HE, Masson, toluidine blue staining and SEM confirmed that the implanted biomaterials were closely connected to the bone defect and that no rejection had taken place. The n-CDHA/PAA biomaterials induced differentiation of a large number of chondrocytes. New bone trabecula began to form at 4 weeks after implanting n-CDHA/PAA biomaterials, and lamellar bone gradually formed at 12 weeks and 24 weeks after implantation. Routine blood and kidney function tests showed no significant changes at 2 weeks and 24 weeks after implantation of both biomaterials. Conclusion n-CDHA/PAA composites showed good compatibility in in vivo model. In this study, n-CDHA/PAA were found to be safe, nontoxic, and biologically active in bone repair. PMID:26504382

Endothelial Progenitor Cells and Kidney Diseases.

PubMed

Ozkok, Abdullah; Yildiz, Alaattin

2018-05-10

Endothelial progenitor cells (EPC) are bone marrow derived or tissue-resident cells that play major roles in the maintenance of vascular integrity and repair of endothelial damage. Although EPCs may be capable of directly engrafting and regenerating the endothelium, the most important effects of EPCs seem to be depended on paracrine effects. In recent studies, specific microvesicles and mRNAs have been found to mediate the pro-angiogenic and regenerative effects of EPCs on endothelium. EPC counts have important prognostic implications in cardiovascular diseases (CVD). Uremia and inflammation are associated with lower EPC counts which probably contribute to increased CVD risks in patients with chronic kidney disease. Beneficial effects of the EPC therapies have been shown in studies performed on different models of CVD and kidney diseases such as acute and chronic kidney diseases and glomerulonephritis. However, lack of a clear definition and specific marker of EPCs is the most important problem causing difficulties in interpretation of the results of the studies investigating EPCs. © 2018 The Author(s). Published by S. Karger AG, Basel.

Effects of uric acid on kidney function decline differ depending on baseline kidney function in type 2 diabetic patients.

PubMed

Hanai, Ko; Tauchi, Eriko; Nishiwaki, Yui; Mori, Tomomi; Yokoyama, Yoichi; Uchigata, Yasuko; Babazono, Tetsuya

2018-05-30

Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.

Prognostic Value of Improved Kidney Function After Transcatheter Aortic Valve Implantation for Aortic Stenosis.

PubMed

Nijenhuis, Vincent Johan; Peper, Joyce; Vorselaars, Veronique M M; Swaans, Martin J; De Kroon, Thom; Van der Heyden, Jan A S; Rensing, Benno J W M; Heijmen, Robin; Bos, Willem-Jan W; Ten Berg, Jurrien M

2018-05-15

Transcatheter aortic valve implantation (TAVI) is associated with acute kidney injury (AKI), but can also improve the kidney function (IKF). We assessed the effects of kidney function changes in relation to baseline kidney function on 2-year clinical outcomes after TAVI. In total, 639 consecutive patients with aortic stenosis who underwent TAVI were stratified into 3 groups according to the ratio of serum creatinine post- to pre-TAVI: IKF (≤0.80; n = 95 [15%]), stable kidney function (0.80 to 1.5; n = 477 [75%]), and AKI (≥1.5; n = 67 [10%]). Different AKI risk scores were compared using receiving-operator characteristics. Median follow-up was 24 (8 to 44) months. At 3 months, the increase in estimated glomerular filtration rate in the IKF group remained, and the decreased estimated glomerular filtration rate in the AKI group recovered. Compared with a stable kidney function, AKI showed a higher 2-year mortality rate (adjusted hazard ratio [HR] 3.69, 95% confidence interval [CI] 2.43 to 5.62) and IKF a lower mortality rate (adjusted hazard ratio 0.53, 95% CI 0.30 to 0.93). AKI also predicted major and life-threatening bleeding (adjusted odds ratio 2.94, 95% CI 1.27 to 6.78). Independent predictors of AKI were chronic kidney disease and pulmonary hypertension. Independent predictors of IKF were female gender, a preserved kidney function, absence of atrial fibrillation, and hemoglobin level. Established AKI risk scores performed moderately and did not differentiate between AKI and IKF. In conclusion, AKI is transient and is independently associated with a higher mortality rate, whereas IKF is sustained and is associated with a lower mortality rate. These effects are independent of baseline kidney function. Further studies are warranted to investigate the role of IKF and generate a dedicated prediction model. Copyright © 2018 Elsevier Inc. All rights reserved.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bone histomorphometry in de novo renal transplant recipients indicates a further decline in bone resorption 1 year posttransplantation.

PubMed

Evenepoel, Pieter; Behets, Geert J; Viaene, Liesbeth; D'Haese, Patrick C

2017-02-01

Renal transplantation is believed to have a major impact on bone health. The present prospective observational bone biopsy study aimed to define the natural history of bone histomorphometry parameters in contemporaneous de novo renal transplant recipients. Paired bone biopsies were performed at the time of transplantation and at one-year posttransplantation in an unselected cohort of 36 patients referred for deceased kidney replacement. Parameters of mineral metabolism and circulating bone turnover markers were monitored as well. Static parameters of bone formation and especially bone resorption being already low-normal in the majority of patients at the time of renal transplantation, further declined during the first posttransplant year. However, interindividual variation was substantial, and significance was reached only for bone resorption parameters. Bone mineralization and trabecular bone volume were within the normal range at the time of transplantation (83.3% and 91.7% of graft recipients, respectively) and showed little change one-year posttransplantation. Changes in osteoclast number were paralleled by changes in circulating tartrate-resistant acid phosphatase 5b levels. Finally, cumulative glucocorticoid dose, but not the posttransplantation parathyroid hormone level, associated with trabecular bone loss. Thus, the impact of renal transplantation on bone histomorphometry is limited with only bone resorption, being already low at the time of transplantation, showing a further decline. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Protecting Space Travelers from Kidney Stones: Renal Stone Risk During Space Flight

NASA Technical Reports Server (NTRS)

Whitson, Peggy; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

2002-01-01

Renal stones, popularly known as kidney or bladder stones, are small rock-like objects formed in the kidneys or urinary tract by deposits of calcium and other minerals. The problem arises when the stones block the drainage of the kidney, resulting in urinary obstruction and pain. Passing these stones can be one of the most painful experiences a person will endure so doctors often prescribe pain relievers to ease the experience. Drinking plenty of fluids, which help flush waste out of the body, and eating a well-balanced diet are the first steps to preventing stones. For individuals at risk, this may not be enough, and a doctor may recommend a special diet and medications. Unfortunately, approximately 60 percent of people who have had a renal stone will experience a recurrence. This is particularly true of men, who are four to five times more likely to develop stones than women. Renal stones do not discriminate based on age; even children are at risk. Astronauts are particularly at risk of developing renal stones because they lose bone and muscle mass; calcium, other minerals, and protein normally used for bone and muscle end up in the bloodstream and then in the kidneys. Without plenty of fluid to wash them away, crystals can form and then grow into stones. This factor compounds the risk for astronauts, since they also perceive that they are less thirsty in space and will drink less than normal during the mission. To minimize all of these factors, doctors must instead treat the stone-forming compounds with medication. This study will use potassium citrate to reduce the risk of stone formation. Renal stones are never convenient, but they are a particular concern for astronauts who have limited access to treatment during flight. Researchers are examining how earthbound preventions for renal stone formation work in flight, ensuring missions are not ended prematurely due to this medical condition. During STS-107, earthbound preventions and treatments become astronauts' gain.

Activation of Bone Morphogenetic Protein 4 Signaling Leads to Glomerulosclerosis That Mimics Diabetic Nephropathy*

PubMed Central

Tominaga, Tatsuya; Abe, Hideharu; Ueda, Otoya; Goto, Chisato; Nakahara, Kunihiko; Murakami, Taichi; Matsubara, Takeshi; Mima, Akira; Nagai, Kojiro; Araoka, Toshikazu; Kishi, Seiji; Fukushima, Naoshi; Jishage, Kou-ichi; Doi, Toshio

2011-01-01

Diabetic nephropathy (DN) is the most common cause of chronic kidney disease. We have previously reported that Smad1 transcriptionally regulates the expression of extracellular matrix (ECM) proteins in DN. However, little is known about the regulatory mechanisms that induce and activate Smad1. Here, bone morphogenetic protein 4 (Bmp4) was found to up-regulate the expression of Smad1 in mesangial cells and subsequently to phosphorylate Smad1 downstream of the advanced glycation end product-receptor for advanced glycation end product signaling pathway. Moreover, Bmp4 utilized Alk3 and affected the activation of Smad1 and Col4 expressions in mesangial cells. In the diabetic mouse, Bmp4 was remarkably activated in the glomeruli, and the mesangial area was expanded. To elucidate the direct function of Bmp4 action in the kidneys, we generated transgenic mice inducible for the expression of Bmp4. Tamoxifen treatment dramatically induced the expression of Bmp4, especially in the glomeruli of the mice. Notably, in the nondiabetic condition, the mice exhibited not only an expansion of the mesangial area and thickening of the basement membrane but also remarkable albuminuria, which are consistent with the distinct glomerular injuries in DN. ECM protein overexpression and activation of Smad1 in the glomeruli were also observed in the mice. The mesangial expansion in the mice was significantly correlated with albuminuria. Furthermore, the heterozygous Bmp4 knock-out mice inhibited the glomerular injuries compared with wild type mice in diabetic conditions. Here, we show that BMP4 may act as an upstream regulatory molecule for the process of ECM accumulation in DN and thereby reveals a new aspect of the molecular mechanisms involved in DN. PMID:21471216

Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney.

PubMed

Drake, Keri A; Adam, Mike; Mahoney, Robert; Potter, S Steven

2018-04-20

Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

Age at Immigration and Kidney Function among Self-Identified Healthy Africans in the United States.

PubMed

Ali, Mana; Mwendwa, Denée T; Sims, Regina; Ricks, Madia; Sumner, Anne E

2016-02-01

Kidney disease disparately affects those of African descent. Age trends have generally been established for kidney function in the overall US population, but the contribution of age at the time of immigration for African immigrants is unknown. To examine the independent and joint effects of age and age at the time of immigration, and kidney function. Estimated glomerular filtration rate (eGFR) was calculated for 93 African immigrants (60 % male; mean age = 33.5). Hierarchical regression and post hoc analyses revealed a significant age × age at the time of immigration interaction after accounting for traditional risk factors among those who immigrated at age ≤21. Younger age at the time of immigration to the US may exacerbate an inverse relationship between age and kidney function in a self-identified healthy African immigrant sample. Investigation of biopsychosocial factors associated with kidney health among African immigrants is warranted.

Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

PubMed

Lang, Joshua; Katz, Ronit; Ix, Joachim H; Gutierrez, Orlando M; Peralta, Carmen A; Parikh, Chirag R; Satterfield, Suzanne; Petrovic, Snezana; Devarajan, Prasad; Bennett, Michael; Fried, Linda F; Cummings, Steven R; Sarnak, Mark J; Shlipak, Michael G

2018-06-01

Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Lower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

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

PubMed

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

2015-11-11

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

Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery

ClinicalTrials.gov

2018-02-27

Bone Cancer; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma

Lead Poisoning: A Need for Education.

ERIC Educational Resources Information Center

Lipnickey, Susan Cross

1981-01-01

Each year approximately 200 children die of lead poisoning. Especially vulnerable to the toxic effects of lead poisoning are the nervous system, kidneys, and the bones. Physiological effects of lead on the school-age child, screening processes, and roles of school personnel in dealing with suspected victims of lead poisoning are discussed. (JN)

Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma

ClinicalTrials.gov

2018-02-09

Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Supratentorial Primitive Neuroectodermal Tumor; Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Extraosseous Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Peripheral Primitive Neuroectodermal Tumor of the Kidney; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Concentrations of heavy metals in American woodcock harvested in Connecticut.

PubMed

Hiller, Brian J; Barclay, John S

2011-01-01

The American woodcock is an important migratory species to both consumptive and nonconsumptive users throughout the species range. Woodcock populations have been declining steadily since surveys began in 1968. Laboratory and field studies have demonstrated several adverse effects associated with metals in other species, which has led to their inclusion as potential contributing factors to the woodcock population decline. We investigated the concentrations of arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb), and selenium (Se) in pectoral muscle (n = 100), livers (n = 108), and kidneys (n = 104) and Pb in wing bones (n = 53) from woodcock harvested in Connecticut. Cd concentrations were elevated in 99% of woodcock livers and kidneys; 30% of kidneys were above 100 μg/g dry weight, a Cd level of reported adverse tissue and reproductive effects in other species. Hg and Cr concentrations were below current biologically significant thresholds. Asc, Pb, and Se in soft tissues were associated with lead shot use in collection. Se in 24% of livers was above 10 μg/g dry weight, the reported threshold for avian health. Wing-bone Pb was elevated above 20 μg/g in 61% of adults and 23% of juveniles examined. Our findings indicate that woodcock are being exposed to potentially damaging levels of at least two metals with known effects in other species.

Cyclosporine use and male gender are independent determinants of avascular necrosis after kidney transplantation: a cohort study.

PubMed

Schachtner, Thomas; Otto, Natalie M; Reinke, Petra

2018-06-03

Kidney transplant recipients (KTRs) are at increased risk of avascular necrosis (AVN) due to bone disorder, steroid use and common comorbidities. However, knowledge on risk factors and outcomes of AVN among KTRs in the modern era of immunosuppression remains scarce. We analysed 765 KTRs between 2001 and 2013 for AVN. Cases of symptomatic AVN were diagnosed by hip X-ray, radioisotope bone scan or magnetic resonance imaging. We evaluated risk factors and clinical characteristics of AVN. KTRs showed a constant incidence rate of AVN of 4.1% at 10 years after transplantation. The use of cyclosporine compared with tacrolimus was identified as an independent risk factor, with a rate of 8.0% compared with 2.7% at 10 years (P < 0.01). In addition, male gender was independently associated with AVN (P = 0.047). Eighty-three per cent of AVN cases were of the femoral head and treated operatively. None of the operated KTRs experienced complications in the long term. Thirty-three per cent of KTRs had bilateral AVN. Ninety-two per cent of KTRs showed AVN at the allograft side. The decreasing incidence of AVN may be attributed to the replacement of cyclosporine by tacrolimus over the last decade. Our data raise the hypothesis of an ischaemic steal syndrome due to the allograft kidney impacting AVN at the allograft side.

Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

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

Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar

2010-10-26

Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstratedmore » that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.« less

Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

NASA Astrophysics Data System (ADS)

Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar; Karmakar, Sougata; Mazumdar, Debasis

2010-10-01

Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstrated that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.

Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

2016-02-01

The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

PubMed Central

Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

2017-01-01

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

Awareness level of kidney functions and diseases among adults in a Nigerian population

PubMed Central

Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

Lower Serum Creatinine Is Associated with Low Bone Mineral Density in Subjects without Overt Nephropathy

PubMed Central

Huh, Ji Hye; Choi, Soo In; Lim, Jung Soo; Chung, Choon Hee; Shin, Jang Yel; Lee, Mi Young

2015-01-01

Background Low skeletal muscle mass is associated with deterioration of bone mineral density. Because serum creatinine can serve as a marker of muscle mass, we evaluated the relationship between serum creatinine and bone mineral density in an older population with normal renal function. Methods Data from a total of 8,648 participants (4,573 men and 4,075 postmenopausal women) aged 45–95 years with an estimated glomerular filtration rate >60 ml/min/1.73 m2 were analyzed from the Fourth Korea National Health and Nutrition Examination Survey (2008–2010). Bone mineral density (BMD) and appendicular muscle mass (ASM) were measured using dual-energy X-ray absorptiometry. Receiver operating characteristic curve analysis revealed that the cut points of serum creatinine for sarcopenia were below 0.88 mg/dl in men and 0.75 mg/dl in women. Subjects were divided into two groups: low creatinine and upper normal creatinine according to the cut point value of serum creatinine for sarcopenia. Results In partial correlation analysis adjusted for age, serum creatinine was positively associated with both BMD and ASM. Subjects with low serum creatinine were at a higher risk for low BMD (T-score ≤ –1.0) at the femur neck, total hip and lumbar spine in men, and at the total hip and lumbar spine in women after adjustment for confounding factors. Each standard deviation increase in serum creatinine was significantly associated with reduction in the likelihood of low BMD at the total hip and lumbar spine in both sexes (men: odds ratio (OR) = 0.84 [95% CI = 0.74−0.96] at the total hip, OR = 0.8 [95% CI = 0.68−0.96] at the lumbar spine; women: OR = 0.83 [95% CI = 0.73–0.95] at the total hip, OR=0.81 [95% CI = 0.67–0.99] at the lumbar spine). Conclusions Serum creatinine reflected muscle mass, and low serum creatinine was independently associated with low bone mineral density in subjects with normal kidney function. PMID:26207750

[Bone metastases pain in the elderly].

PubMed

Chouahnia, K; Luu, M; Baba-Hamed, N; Des Guetz, G

2009-05-20

Every year in Europe and in USA, more than 60% of new cases of cancer are diagnosed at the patient's of more than 65 years with a mortality of more than 70%. Pain, is a major symptom which often accompanies cancer. It is always painful and intolerable, notably when pain is linked to bone metastases to elderly patients often poly pathological. In 1/3 of cases pain is present at the time of diagnosis of cancer and in 2/3 of cases at the advanced diseases. The bone metastases occupy the third place after the pulmonary and liver metastases. They are in order of frequency linked in breast cancer, the kidney and the prostate cancer. Bone metastases are at the origin of the loss of the elderly autonomy, with for consequence an impairment of quality of life. Validated tools are at now available to assess this pain. The different treatments offered in bone metastases pain are: the chemotherapy, the surgery, radiotherapy, bisphosphonates and analgesic treatment.

Association between physical activity and kidney function: National Health and Nutrition Examination Survey.

PubMed

Hawkins, Marquis S; Sevick, Mary Ann; Richardson, Caroline R; Fried, Linda F; Arena, Vincent C; Kriska, Andrea M

2011-08-01

Chronic kidney disease is a condition characterized by the deterioration of the kidney's ability to remove waste products from the body. Although treatments to slow the progression of the disease are available, chronic kidney disease may eventually lead to a complete loss of kidney function. Previous studies have shown that physical activities of moderate intensity may have renal benefits. Few studies have examined the effects of total movement on kidney function. The purpose of this study was to determine the association between time spent at all levels of physical activity intensity and sedentary behavior and kidney function. Data were obtained from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey, a cross-sectional study of a complex, multistage probability sample of the US population. Physical activity was assessed using an accelerometer and questionnaire. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease study formula. To assess linear associations between levels of physical activity and sedentary behavior with log-transformed estimated GFR (eGFR), linear regression was used. In general, physical activity (light and total) was related to log eGFR in females and males. For females, the association between light and total physical activity with log eGFR was consistent regardless of diabetes status. For males, the association between light and total physical activity and log eGFR was only significant in males without diabetes. When examining the association between physical activity, measured objectively with an accelerometer, and kidney function, total and light physical activities were found to be positively associated with kidney function.

[Vitamin K metabolism. Menaquinone-4 (MK-4) formation from ingested VK analogues and its potent relation to bone function].

PubMed

Komai, Michio; Shirakawa, Hitoshi

2007-11-01

Phylloquinone (vitamin K(1) = VK(1)) and the menaquinones (MK-n, or vitamin K(2) = VK(2)) are naturally occurring forms of VK. Most of the menaquinone series are synthesized by microorganisms, but we have reported that MK-4 is usual in being synthesized by the conversion of orally ingested VK(1) or MK-n in the major tissues of germfree rats and mice which lack their intestinal microflora. This result led us to deny 1960's Martius' hypothesis that described the participation of bacterial enzyme of the intestinal flora to this conversion. VK acts as a cofactor in the posttranslational synthesis of gamma-carboxyglutamic acid (Gla) from glutamic acid (Glu) residues in the nascent Gla-protein molecule. Therefore, VK is essential for blood coagulation (various clotting factors) and bone structure (as osteocalcin [OC = BGP] and matrix Gla-protein [MGP] in mammals. In addition to the liver, VK is found in the bone, brain, heart, testis, kidney, pancreas and salivary glands mainly as MK-4, and it has been reported that MK-4 itself has specific biological activities in these tissues beside Gla-protein formation. However, the physiological role of MK-4 in these organs has not been fully understood yet. Recently MK-4 has been attracted the attention of researchers due to its activities such as apoptotic activity on the osteoclast cells and leukemia cells, SXR/PXR ligand, and so on. We further review the potent important physiological role of MK-4 in the bone as well as other major tissues.

Diagnosis of Iron-Deficiency Anemia in Chronic Kidney Disease.

PubMed

Bahrainwala, Jehan; Berns, Jeffrey S

2016-03-01

Anemia is a common and clinically important consequence of chronic kidney disease (CKD). It is most commonly a result of decreased erythropoietin production by the kidneys and/or iron deficiency. Deciding on the appropriate treatment for anemia associated with CKD with iron replacement and erythropoietic-stimulating agents requires an ability to accurately diagnose iron-deficiency anemia. However, the diagnosis of iron-deficiency anemia in CKD patients is complicated by the relatively poor predictive ability of easily obtained routine serum iron indices (eg, ferritin and transferrin saturation) and more invasive gold standard measures of iron deficiency (eg, bone marrow iron stores) or erythropoietic response to supplemental iron. In this review, we discuss the diagnostic utility of currently used serum iron indices and emerging alternative markers of iron stores. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathogenesis of renal failure in multiple myeloma: any role of contrast media?

PubMed

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

PubMed Central

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

Cardio-renal syndromes: a systematic approach for consensus definition and classification.

PubMed

Ronco, Claudio; Ronco, Federico

2012-03-01

The "Cardio-Renal Syndrome" (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded to five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Kidneys: Key Modulators of HDL Levels and Function

PubMed Central

Yang, Haichun; Fogo, Agnes B.; Kon, Valentina

2016-01-01

Purpose of review This review will examine advances in our understanding of the role kidneys play in HDL metabolism and the effect on levels, composition, and function of HDL particles. Recent findings Components of the HDL particles can cross the glomerular filtration barrier. Some of these components, including apolipoproteins and enzymes involved in lipid metabolism, are taken up by the proximal tubule and degraded, modified, salvaged/returned to the circulation, or lost in the urine. Injury of the glomerular capillaries or tubules can affect these intrarenal processes and modify HDL. Changes in the plasma and urine levels of HDL may be novel markers of kidney damage and/or mechanism(s) of kidney disease. Summary The kidneys have a significant role in metabolism of individual HDL components, which in turn modulate HDL levels, composition and functionality of HDL particles. These intrarenal effects may be useful markers of kidney damage and have consequences on kidney-related perturbations in HDL. PMID:27008596

Vitamin D and renal outcome: the fourth outcome of CKD-MBD? Oshima Award Address 2015.

PubMed

Hamano, Takayuki

2018-04-01

Bone fracture, cardiovascular events, and mortality are three outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD), and the umbrella concept originally described for dialysis patients. The reported association of serum phosphorus or fibroblast growth factor 23 (FGF23) levels with renal outcome suggests that the fourth relevant outcome of CKD-MBD in predialysis patients is renal outcome. We found that proteinuria of 2+ or greater with a dipstick test was associated with low vitamin D status due to urinary loss of 25-hydroxyvitamin D (25D). Moreover, active vitamin D or its analogues decrease proteinuria. Given our finding that maxacalcitol does not repress renin, the reduction of proteinuria by this agent is likely due to direct upregulation of the nephrin and podocin in podocytes. Moreover, this agent downregulates the mesenchymal marker desmin in podocytes and blocks transforming growth factor-beta autoinduction, leading to attenuation of renal fibrosis in a unilateral ureteral obstructive (UUO) model. These facts are reminiscent of the suppression of epithelial-mesenchymal transition (EMT) by vitamin D. EMT blockage may explain our finding that vitamin D prescription in renal transplant recipients is associated with a lower incidence of cancer. We also reported that low vitamin D status and high FGF23 levels predict a worse renal outcome. However, administration of massive doses of 25D exacerbates renal fibrosis in UUO kidneys in 1alpha-hydroxylase knockout mice. Moreover, FGF23 inhibits 1alpha-hydroxylase in proximal tubules and monocytes. Taken together, local 1,25(OH) 2 D in the kidney tissue but not 25D seems to protect the kidney.

FGFR Inhibitor Ameliorates Hypophosphatemia and Impaired Engrailed-1/Wnt Signaling in FGF2 High Molecular Weight Isoform Transgenic Mice.

PubMed

Du, Erxia; Xiao, Liping; Hurley, Marja M

2016-09-01

High molecular weight FGF2 transgenic (HMWTg) mouse phenocopies the Hyp mouse, homolog of human X-linked hypophosphatemic rickets with hypophosphatemis, and abnormal FGF23, FGFR, Klotho signaling in kidney. Since abnormal Wnt signaling was reported in Hyp mice we assessed whether Wnt signaling was impaired in HMWTg kidneys and the effect of blocking FGF receptor (FGFR) signaling. Bone mineral density and bone mineral content in female HMWTg mice were significantly reduced. HMWTg mice were gavaged with FGFR inhibitor NVP-BGJ398, or vehicle and were euthanized 24 h post treatment. Serum phosphate was significantly reduced and urine phosphate was significantly increased in HMWTg and was rescued by NVP-BGJ398. Analysis of kidneys revealed a significant reduction in Npt2a mRNA in HMWTg that was significantly increased by NVP-BGJ398. Increased FGFR1, KLOTHO, P-ERK1/2, and decreased NPT2a protein in HMWTg were rescued by NVP-BGJ398. Wnt inhibitor Engrailed-1 mRNA and protein was increased in HMWTg and was decreased by BGJ398. Akt mRNA and protein was decreased in HMWTg and was increased by NVP-BGJ398. The active form of glycogen synthase 3 beta (pGSK3-β) and phosphor-β-catenin were increased in HMWTg and were both decreased by NVP-BGJ398 while decreased active-β-catenin in HMWTg was increased by NVP-BGJ398. We conclude that FGFR blockade rescued hypophosphatemia by regulating FGF and WNT signaling in HMWTg kidneys. J. Cell. Biochem. 117: 1991-2000, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Systemic molecular and cellular changes induced in rats upon inhalation of JP-8 petroleum fuel vapor.

PubMed

Hanas, Jay S; Bruce Briggs, G; Lerner, Megan R; Lightfoot, Stan A; Larabee, Jason L; Karsies, Todd J; Epstein, Robert B; Hanas, Rushie J; Brackett, Daniel J; Hocker, James R

2010-05-01

Limited information is available regarding systemic changes in mammals associated with exposures to petroleum/hydrocarbon fuels. In this study, systemic toxicity of JP-8 jet fuel was observed in a rat inhalation model at different JP-8 fuel vapor concentrations (250, 500, or 1000 mg/m(3), for 91 days). Gel electrophoresis and mass spectrometry sequencing identified the alpha-2 microglobulin protein to be elevated in rat kidney in a JP-8 dose-dependent manner. Western blot analysis of kidney and lung tissue extracts revealed JP-8 dependent elevation of inducible heat shock protein 70 (HSP70). Tissue changes were observed histologically (hematoxylin and eosin staining) in liver, kidney, lung, bone marrow, and heart, and more prevalently at medium or high JP-8 vapor phase exposures (500-1000 mg/m(3)) than at low vapor phase exposure (250 mg/m(3)) or non-JP-8 controls. JP-8 fuel-induced liver alterations included dilated sinusoids, cytoplasmic clumping, and fat cell deposition. Changes to the kidneys included reduced numbers of nuclei, and cytoplasmic dumping in the lumen of proximal convoluted tubules. JP-8 dependent lung alterations were edema and dilated alveolar capillaries, which allowed clumping of red blood cells (RBCs). Changes in the bone marrow in response to JP-8 included reduction of fat cells and fat globules, and cellular proliferation (RBCs, white blood cells-WBCs, and megakaryocytes). Heart tissue from JP-8 exposed animals contained increased numbers of inflammatory and fibroblast cells, as well as myofibril scarring. cDNA array analysis of heart tissue revealed a JP-8 dependent increase in atrial natriuretic peptide precursor mRNA and a decrease in voltage-gated potassium (K+) ion channel mRNA.

Cardiorenal syndrome: new developments in the understanding and pharmacologic management.

PubMed

House, Andrew A

2013-10-01

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.

Computed Tomography Volumetry in Preoperative Living Kidney Donor Assessment for Prediction of Split Renal Function.

PubMed

Wahba, Roger; Franke, Mareike; Hellmich, Martin; Kleinert, Robert; Cingöz, Tülay; Schmidt, Matthias C; Stippel, Dirk L; Bangard, Christopher

2016-06-01

Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 ± 29.1 cm, 151.2 ± 35.4 and 93.9 ± 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, -7.7% to 8.6%; MELV vs MAG3 0.4%, -8.9% to 9.7%; RCV vs MAG3 0.8%, -9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3-SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF.

[Kidney stone formation during space flight and long-term bed rest].

PubMed

Okada, Atsushi; Ichikawa, Jun; Tozawa, Keiichi

2011-10-01

Microgravity environment like space flight or a condition requiring long-term bed-rest increase bone resorption and decrease bone formation, inducing the rapid decrease of bone minerals to osteoporosis. Bone mineral loss increases urinary calcium excretion and the risk of urinary stone formation. To clarify the influence of the conditions on renal stone formation, a 90-day bed rest test was performed to analyze the mechanism of microgravity or bed rest-induced stone formation and prevention by bisphosphonate medication and bed-rest exercise. As the results, renal stone formation was observed in control and exercise groups and no stone was seen in the medication group. In the medication group, urinary calcium excretion and relative supersaturation of calcium oxalate were lower than in the control group throughout the bed-rest and recovery period. Bisphosphonate is useful for the prevention of renal stone formation during space flight and long-term bed-rest.

Renoprotective effects of asialoerythropoietin in diabetic mice against ischaemia-reperfusion-induced acute kidney injury.

PubMed

Nakazawa, Jun; Isshiki, Keiji; Sugimoto, Toshiro; Araki, Shin-Ichi; Kume, Shinji; Yokomaku, Yukiyo; Chin-Kanasaki, Masami; Sakaguchi, Masayoshi; Koya, Daisuke; Haneda, Masakazu; Kashiwagi, Atsunori; Uzu, Takashi

2010-02-01

Diabetic patients are at higher risk of failure to recover after acute kidney injury, however, the mechanism and therapeutic strategies remain unclear. Erythropoietin is cytoprotective in a variety of non-haematopoietic cells. The aim of the present study was to clarify the mechanism of diabetes-related acceleration of renal damage after ischaemia-reperfusion injury and to examine the therapeutic potential of asialoerythropoietin, a non-haematopoietic erythropoietin derivative, against ischaemia-reperfusion-induced acute kidney injury in diabetic mice. C57BL/6J mice with and without streptozotocin-induced diabetes were subjected to 30 min unilateral renal ischaemia-reperfusion injury at 1 week after induction of diabetes. They were divided into four group: (i) non-diabetic plus ischaemia-reperfusion injury; (ii) non-diabetic plus ischaemia-reperfusion injury plus asialoerythropoietin (3000 IU/kg bodyweight); (iii) diabetic plus ischaemia-reperfusion injury; and (iv) diabetic plus ischemia-reperfusion injury plus asialoerythropoietin. Experiments were conducted at the indicated time periods after ischaemia-reperfusion injury. Ischaemia-reperfusion injury of diabetic kidney resulted in significantly low protein expression levels of bcl-2, an anti-apoptotic molecule, and bone morphogenetic protein-7 (BMP-7), an anti-fibrotic and pro-regenerative factor, compared with non-diabetic kidneys. Diabetic kidney subsequently showed severe damage including increased tubular cell apoptosis, tubulointerstitial fibrosis and decreased tubular proliferation, compared with non-diabetic kidney. Treatment with asialoerythropoietin induced bcl-2 and BMP-7 expression in diabetic kidney and decreased tubular cell apoptosis, tubulointerstitial fibrosis and accelerated tubular proliferation. Reduced induction bcl-2 and BMP-7 may play a role in the acceleration of renal damage after ischaemia-reperfusion injury in diabetic kidney. The renoprotective effects of asialoerythropoietin on acute kidney injury may be mediated through the induction of bcl-2 and BMP-7.

When Your Child Needs a Kidney Transplant

MedlinePlus

... Search English Español When Your Child Needs a Kidney Transplant KidsHealth / For Parents / When Your Child Needs ... to monitor their new kidney function. About the Kidneys Kidneys are bean-shaped organs located near the ...

Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney disease.

PubMed

Yadav, Ashok Kumar; Kumar, Vivek; Banerjee, Debasish; Gupta, Krishan Lal; Jha, Vivekanand

2018-06-01

Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤ 20 ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At baseline, serum levels of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml, IQR;140-260 pg/ml and placebo - median;180 pg/ml, IQR; 140-240 pg/ml, p = 0.67). 16 weeks after cholecalciferol supplementation, there was no change in level of sclerostin (mean change;1.10 pg/ml, 95%CI; -27.34 to 29.34 pg/ml, p = 0.25). However, a significant decrease in sclerostin level was noted in the placebo group (mean change; -31.94 pg/ml, 95%CI; -54.76 to -9.13 pg/ml, p = 0.002). Change (Δ) in sclerostin level at 16 weeks correlated negatively with Δ eGFR (r = -0.20, p = 0.03) and positively with Δuric acid (r = 0.37, p < 0.001) but not with Δ25(OH) D (r = 0.06, p = 0.54), Δ iPTH (r = - 0.03, p = 0.78) ΔFGF23 (r = - 0.08, p = 0.38) and Δ125 (OH) 2 D (r = - 0.04, p = 0.65). In conclusion, high dose cholecalciferol supplementation did not change sclerostin levels in non-diabetic stage 3-4 CKD subjects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Increased bone density in mice lacking the proton receptor, OGR1

PubMed Central

Krieger, Nancy S.; Yao, Zhenqiang; Kyker-Snowman, Kelly; Kim, Min Ho; Boyce, Brendan F.; Bushinsky, David A.

2016-01-01

Chronic metabolic acidosis stimulates cell-mediated calcium efflux from bone through osteoblastic prostaglandin E2-induced stimulation of RANKL leading to increased osteoclastic bone resorption. Osteoblasts express the proton-sensing G-protein coupled receptor, OGR1, which activates IP3-mediated intracellular calcium. Proton-induced osteoblastic intracellular calcium signaling requires OGR1, suggesting OGR1 is the sensor activated during acidosis to cause bone resorption. Growing mice produce large amounts of metabolic acids which must be buffered, primarily by bone, prior to excretion by the kidney. Here we tested whether lack of OGR1 inhibits proton-induced bone resorption by measuring bone mineral density by μCT and histomorphometry in 8 week old male OGR1−/− and C57/Bl6 wild type mice. OGR1−/− mice have normal skeletal development with no atypical gross phenotype. Trabecular and cortical bone volume was increased in tibiae and vertebrae from OGR1−/−. There were increased osteoblast numbers on the cortical and trabecular surfaces of tibiae from OGR1−/− mice, increased endocortical and trabecular bone formation rates, and osteoblastic gene expression. Osteoclast numbers and surface were increased in tibiae of OGR1−/− mice. Thus, in rapidly growing mice, lack of OGR1 leads to increased bone mass with increased bone turnover and a greater increase in bone formation than resorption. This supports the important role of the proton receptor, OGR1, in the response of bone to protons. PMID:26880453

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

PubMed

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

2010-06-01

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

[The effects of graphene quantum dots on hematopoietic system in rats].

PubMed

Wang, Ting-jian; Wang, Sha-li

2016-01-01

To study the effects of graphene quantum dots (GQDs) on hematopoietic system in rats. Thirty male SD rats were randomly divided into three groups (n = 10): control group, high dose group (10 mg/kg · d), low dose group (5 mg/kg · d), The rats in experimental group were intravenous injected with GQDs for 28 days and those in control group were injected with normal saline at the same volume. Routine blood and the function of liver and kidney were detected by instrument analysis. The cycle and apoptosis of bone marrow mononuclear cells (BMCs) were detected by FCM. The other three only healthy male SD rat bone marrow mononuclear cells (BMCs) were cultured by joining GQDs for 24 h, 48 h,72 h in vitro, the proliferation was assayed by CCK-8, the content of granulocyte macrophage colony stimulating factor (GM-CSF) from cultural supernatants were detected by ELISA. The amount of red blood cell and concentration of hemoglobin from experimental group were increased significantly compared with those of control groups (P < 0.05), the concentration of triglyceride and high density lipoprotein were decreased. DNA synthesis period was prolonged (P < 0.01), there was no significant difference in apoptosis. BMCs were promoted proliferation clearly after using GQDs for 72 h (P < 0.05). The content of GM-CSF was increased (P < 0.01) . GQDs may promote hematopoietic function in rats.

Evaluation of the antihypertensive properties of yellow passion fruit pulp (Passiflora edulis Sims f. flavicarpa Deg.) in spontaneously hypertensive rats.

PubMed

Konta, Eliziane Mieko; Almeida, Mara Ribeiro; do Amaral, Cátia Lira; Darin, Joana Darc Castania; de Rosso, Veridiana V; Mercadante, Adriana Zerlotti; Antunes, Lusânia Maria Greggi; Bianchi, Maria Lourdes Pires

2014-01-01

Various species of the genus Passiflora have been extensively used in traditional medicine as sedatives, anxiolytics, diuretics and analgesics. In the present study, after the identification and quantification of phytochemical compounds from yellow passion fruit pulp by liquid chromatography-photodiode array-mass spectrometry (HPLC-PDA-MS/MS), its antihypertensive effect was investigated on spontaneously hypertensive rats. Additionally, the renal function, evaluated by kidney/body weight, serum creatinine, proteinuria, urinary flow, reduced glutathione (GSH) levels and thiobarbituric acid-reactive substances (TBARS) and mutagenicity in bone marrow cells were assessed to evaluate the safety of passion fruit consumption. Yellow passion fruit pulp (5, 6 or 8 g/kg b.w.) was administered by gavage once a day for 5 consecutive days. HLPC-PDA-MS/MS analysis revealed that yellow passion fruit pulp contains phenolic compounds, ascorbic acid, carotenoids and flavonoids. The highest dose of passion fruit pulp significantly reduced the systolic blood pressure, increased the GSH levels and decreased TBARS. There were no changes in renal function parameters or the frequency of micronuclei in bone marrow cells. In conclusion, the antihypertensive effect of yellow passion fruit pulp, at least in part, might be due to the enhancement of the antioxidant status. The exact mechanisms responsible by this effect need further investigation. Copyright © 2013 John Wiley & Sons, Ltd.

[How to manage mineral metabolism disorders in renal failure].

PubMed

Jean, Guillaume

2011-11-01

Mineral metabolism abnormalities are frequently observed in patients with chronic kidney disease (CKD). The bone and cardiovascular consequences should lead to the implementation of some adapted strategies for the prevention and treatment on the basis of the physiopathology of the disease and international recommendations. Biological bone markers such as serum parathyroid hormone (PTH) and alkaline phosphatase (ALP) are necessary to classify bone diseases without the need for bone biopsy. Elevated levels of bone markers are detected in cases of secondary hyperparathyroidism (SHPT), whereas decreased levels are observed in cases of adynamic bone disease (ABD). Bone mineral density, however, is not useful for the diagnosis. Vitamin D supplementation and reducing hyperphosphataemia by dietary phosphate-intake restriction, phosphate binders, and dialysis, are the main steps for the prevention of SHPT. Calcitriol analogs and calcimimetics should be used in second line in cases of SHPT. For the treatment of ABD, excess use of calcium salts and calcitriol analogs need to be avoided. Managing these therapies adequately can help maintain the main biological values (i.e. serum PTH, calcium, phosphorus, and ALP) within their recommended ranges. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Association of Kidney Function and Albuminuria With Prevalent and Incident Hypertension: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Huang, Minxuan; Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H.; Astor, Brad C.; Coresh, Josef

2014-01-01

Background Decreased kidney function and kidney damage may predate hypertension, but only a few studies have investigated both types of markers simultaneously, and these studies have obtained conflicting results. Study Design Cross-sectional for prevalent and prospective observational study for incident hypertension. Setting & Participants 9,593 participants from the Atherosclerosis Risk in Communities (ARIC) Study, aged 53-75 years during 1996-1998. Predictors Several markers of kidney function (estimated glomerular filtration rate [eGFR] using serum creatinine and/or cystatin C and two novel markers [β-trace protein and β2-microglobulin]) and one marker of kidney damage (urinary albumin-creatinine ratio [ACR]). Every kidney marker was categorized by its quintiles (top quintile as a reference for eGFRs and bottom quintile for the rest). Outcomes Prevalent and incident hypertension. Measurements Prevalence and HRs of hypertension based on modified Poisson regression and Cox proportional hazards models, respectively. Results There were 4,378 participants (45.6%) with prevalent hypertension at baseline and 2,175 incident hypertension cases during a median follow-up of 9.8 years. While all five kidney function markers were significantly associated with prevalent hypertension, prevalent hypertension was most notably associated with higher ACR (adjusted prevalence ratio, 1.60 [95% CI, 1.50-1.71] for the highest vs lowest ACR quintile). Similarly, ACR was consistently associated with incident hypertension in all models tested (adjusted HR, 1.28 [95% CI, 1.10-1.49] for top quintile), while kidney function markers demonstrated significant associations in some, but not all, models. Even mildly increased ACR (9.14-14.0 mg/g) was significantly associated with incident hypertension. Limitations Self-reported use of antihypertensive medication for defining incident hypertension, single assessment of kidney markers, and relatively narrow age range. Conclusions Although all kidney markers were associated with prevalent hypertension, only elevated albuminuria was consistently associated with incident hypertension, suggesting that kidney damage is more closely related to hypertension than moderate reduction in overall kidney function. PMID:25151408

Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

PubMed

Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Abe, Masami; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-05-26

BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

Integral pharmacological management of bone mineral disorders in chronic kidney disease (part II): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification.

PubMed

Bover, J; Ureña-Torres, P; Lloret, M J; Ruiz, C; DaSilva, I; Diaz-Encarnacion, M M; Mercado, C; Mateu, S; Fernández, E; Ballarin, J

2016-07-01

Chronic kidney disease-mineral and bone disorders (CKD-MBD) are associated with costly complications and dismal hard-outcomes. In two comprehensive articles we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (part 1) and hyperparathyroidism (this part 2), taking into account CKD-accelerated cardiovascular calcification (CVC) processes. Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Here, initial guidance to control hyperparathyroidism is provided, taking into account the presence/absence of CVC. We include also measures for patients at risk of adynamic bone disease or suffering from calciphylaxis. Many epidemiological studies (relating to vitamin D) and thorough analyses of recent randomized clinical trials (of cinacalcet) point towards benefits of attempting to improve biochemical parameters while trying to, at least, avoid progression of CVC by more rational use of intestinal P-binders and low-dose vitamin D derivatives and/or calcimimetics. This approach does not seem to be far away from significantly improving hard-outcomes, at least in the dialysis population. The availability of new drugs and the performance of randomized clinical trials should ultimately lead to define earlier, clearer, and more cost-effective patient stratification and biochemical targets with consequent significant clinical improvements.

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors.

PubMed

Courbebaisse, Marie; Gaillard, François; Tissier, Anne-Marie; Fournier, Catherine; Le Nestour, Alexis; Corréas, Jean-Michel; Slimani-Thevenet, Hind; Martinez, Frank; Léon, Carine; Eladari, Dominique; Timsit, Marc-Olivier; Otal, Philippe; Hignette, Chantal; Friedlander, Gérard; Méjean, Arnaud; Houillier, Pascal; Kamar, Nassim; Legendre, Christophe

2016-08-08

The predictors of long-term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. We conducted a prospective monocentric study including 63 living donors (26 men; 50.3±11.8 years old) who had been evaluated for (51)Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7±0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0±9.4 years old) from another single center during the same time period. For the main cohort, the mean measured GFR was 97.6±13.0 ml/min per 1.73 m(2) before donation and 63.8±9.4 ml/min per 1.73 m(2) at 5 years. Functional gain averaged 16.2±7.2 ml/min per 1.73 m(2) (+35.3%±16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: -0.4 [95% confidence interval (95% CI), -0.5 to -0.1]; body mass index: -0.3 [95% CI, -0.6 to -0.1]; rk-GFR/vol: -55.1 [95% CI, -92.3 to -17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: -0.1 [95% CI, -0.5 to 0.3]; body mass index: -0.9 [95% CI, -1.8 to -0.1]; rk-GFR/vol: -97.6 [95% CI, -137.5 to -57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. For given age and body mass index, the long-term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. Copyright © 2016 by the American Society of Nephrology.

Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

PubMed

George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

2016-01-01

Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).

Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

PubMed

Niu, Yinbo; Li, Chenrui; Pan, Yalei; Li, Yuhua; Kong, Xianghe; Wang, Shuo; Zhai, YuanKun; Wu, Xianglong; Fan, Wutu; Mei, Qibing

2015-01-01

Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. This study investigates the effect of RDE against bone loss induced by simulated microgravity. A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.

PubMed

Sawhney, Simon; Mitchell, Mhairi; Marks, Angharad; Fluck, Nick; Black, Corrinda

2015-01-06

To summarise the evidence from studies of acute kidney injury (AKI) with regard to the effect of pre-AKI renal function and post-AKI renal function recovery on long-term mortality and renal outcomes, and to assess whether these factors should be taken into account in future prognostic studies. A systematic review of observational studies listed in Medline and EMBASE from 1990 to October 2012. All AKI studies in adults with data on baseline kidney function to identify AKI; with outcomes either stratified by pre-AKI and/or post-AKI kidney function, or described by the timing of the outcomes. Long-term mortality and worsening chronic kidney disease (CKD). Of 7385 citations, few studies met inclusion criteria, reported baseline kidney function and stratified by pre-AKI or post-AKI function. For mortality outcomes, three studies compared patients by pre-AKI renal function and six by post-AKI function. For CKD outcomes, two studies compared patients by pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI (compared with AKI alone) was associated with doubling of mortality and a fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function was associated with greater mortality and CKD outcomes in some studies, but findings were inconsistent varying with study design. Two studies also reported that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded by variations in definitions for AKI, CKD and recovery. The long-term prognosis after AKI varies depending on cause and clinical setting, but it may also, in part, be explained by underlying pre-AKI and post-AKI renal function rather than the AKI episode itself. While carefully considered in clinical practice, few studies address these factors and with inconsistent study design. Future AKI studies should report pre-AKI and post-AKI function consistently as additional factors that may modify AKI prognosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Lead in the bone and soft tissues of box turtles caught near smelters

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

Beresford, W.A.; Donovan, M.P.; Henninger, J.M.

1981-09-01

Three box turtles (Terrapene carolina) were caught by small streams in woodland south-east of Glover, MO and one, northeast of Bixby, MO: rural sites of primary lead smelters. Four other turtles were caught in a similar habitat, but distant from industry and main roads. Both groups shared the same food, water, and outside pen in Morgantown, WV. Lead content was assayed by atomic absorption spectrophotometry. Lead concentrations in the liver, kidney, skin, blood, and two long bone shafts were found to be significantly higher in the turtles captured near the smelters.

Systematic review of kidney transplantation functional predictors.

PubMed

Miret Alomar, E; Trilla Herrera, E; Lorente Garcia, D; Regis Placido, L; López Del Campo, R; Cuadras Solé, M; Pont Castellana, T; Moreso Mateos, F; Serón Micas, D; Morote Robles, J

2018-05-01

Kidney transplantation from donors with expanded criteria has increased the pool of kidneys at the cost of a higher risk of short and long-term graft dysfunction. The main issue lies in determining which kidneys will offer acceptable function and survival compared with the risk represented by surgery and subsequent immunosuppression. The objective of our article is to review the current evidence on the tools for predicting the functionality of kidney transplantation from cadaveric donors with expanded criteria and determining the validity for their use in standard practice. We conducted a systematic literature review according to the PRISM criteria, through Medline (http://www.ncbi.nlm.nih.gov) and using the keywords (in isolation or in conjunction) "cadaveric renal transplantation; kidney graft function appraisal, graft function predictors". We selected prospective and retrospective series and review articles. A total of 375 articles were analysed, 39 of which were ultimately selected for review. The predictors of functionality include the following: The donor risk indices; the calculation of the renal functional weight or the assessment of the nephronic mass; the measurement of vascular resistances during perfusion in hypothermia; the measurement of the donor's biomarkers in urine and in the perfusion liquid; the measurement of functional and reperfusion parameters in normothermia; and the measurement of morphological parameters (microscopic and macroscopic) of the target organ. In this article, we present an explanatory summary of each of these parameters, as well as their most recent evidence on this issue. None of the reviewed parameters in isolation could reliably predict renal function and graft survival. There is a significant void in terms of the macroscopic assessment of kidney transplantation. We need to continue developing predictors of renal functionality to accurately define the distribution of each currently available donor kidney. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Hydration Status, Kidney Function, and Kidney Injury in Florida Agricultural Workers.

PubMed

Mix, Jacqueline; Elon, Lisa; Vi Thien Mac, Valerie; Flocks, Joan; Economos, Eugenia; Tovar-Aguilar, Antonio J; Stover Hertzberg, Vicki; McCauley, Linda A

2018-05-01

Recent findings suggest that laboring in hot occupational environments is related to kidney damage in agricultural workers. We examined hydration status and kidney function in 192 Florida agricultural workers. Blood and urine samples were collected over 555 workdays during the summers of 2015 and 2016. Urine-specific gravity (USG), serum creatinine, and other kidney function markers were examined pre- and post-shift on each workday. Multivariable mixed modeling was used to examine the association of risk factors with hydration status and acute kidney injury (AKI). Approximately 53% of workers were dehydrated (USG ≥1.020) pre-shift and 81% post-shift; 33% of participants had AKI on at least one workday. The odds of AKI increased 47% for each 5-degree (°F) increase in heat index. A strikingly high prevalence of dehydration and AKI exists in Florida agricultural workers.

Living with Lowe's Syndrome. A Guide for Families, Friends, and Professionals.

ERIC Educational Resources Information Center

Lowe's Syndrome Association, Inc., West Lafayette, IN.

The document describes Lowe's syndrome, a hereditary condition that affects only males and is typically diagnosed during the first year of life. Effects of Lowe's syndrome on the eyes (cataracts, glaucoma, corneal degeneration, and strabismus) are discussed, as well as related problems with the central nervous system, muscles, kidneys, bones, and…

Impaired Kidney Function and Associated Factors Among Rural Adults With Disabilities in Taiwan.

PubMed

Chen, Chu-Yeh; Chiu, Wen-Nan; Lin, Yu-Chen; Jane, Sui-Hwi; Chiang, Hsin-Hung; Chen, Mei-Yen

2017-04-01

The results of numerous studies indicate that people with disabilities seek more healthcare than those who are not disabled, particularly for conditions such as chronic kidney disease, cardiovascular disease, and obesity. However, little is known about the incidence of impaired kidney function and its associated factors among adults with disabilities in Taiwan. The aim of this study was to explore the prevalence and factors associated with impaired kidney function among adults with disabilities. This descriptive study was nurse led and was conducted as part of a health promotion program for disadvantaged rural adults with disabilities in Chiayi County, Taiwan. Health screening and a health needs survey were conducted between July and December 2013. Kidney function, physiological biomarkers, health-related behaviors, and demographic characteristics were examined. Eight hundred ten rural adults with disabilities were enrolled. The most common disabilities included physical-related disability (33.1%), intellectual-related disability (26.7%), and hearing and vision impairment (18.6%). The prevalence of impaired kidney function in this population was 85%. According to classification for chronic kidney disease, 68.6% were in Stages 1-2, and 16.8% were in Stages 3-4. Univariate analysis showed that impaired kidney function was significantly associated with lower educational level (p < .001), hearing or vision impairment (p < .001), being overweight or obese (p < .05), high systolic blood pressure (p < .01), fasting blood glucose (p < .001), total cholesterol (p < .001), total triglyceride (p < .05), older age (p < .001), smoking (p < .05), chewing betel nuts (p = .001), and low levels of participation in social activities (p < .05). The final logistic regression model showed that residents with disabilities who were older or had less education, high fasting blood glucose, and high total cholesterol tended to have impaired kidney function after adjustment for other potential confounding variables. Most participants showed impaired kidney function. The factors that were found to relate significantly to this impairment include being overweight, having hyperlipidemia, having hypertension, having high fasting blood glucose, and having an unhealthy lifestyle. Because of the lack of symptoms during the early stages of chronic kidney disease, a community-based health promotion program for these factors is an important element in health advocacy for this vulnerable population.

Spacelab

NASA Image and Video Library

1991-06-01

The laboratory module in the cargo bay of the Space Shuttle Orbiter Columbia was photographed during the Spacelab Life Science-1 (SLS-1) mission. SLS-1 was the first Spacelab mission dedicated solely to life sciences. The main purpose of the SLS-1 mission was to study the mechanisms, magnitudes, and time courses of certain physiological changes that occur during space flight, to investigate the consequences of the body's adaptation to microgravity and readjustment to Earth's gravity, and to bring the benefits back home to Earth. The mission was designed to explore the responses of the heart, lungs, blood vessels, kidneys, and hormone-secreting glands to microgravity and related body fluid shifts; examine the causes of space motion sickness; and study changes in the muscles, bones and cells. The five body systems being studied were: The Cardiovascular/Cardiopulmonary System (heart, lungs, and blood vessels), the Renal/Endocrine System (kidney and hormone-secreting organs), the Immune System (white blood cells), the Musculoskeletal System (muscles and bones), and the Neurovestibular System (brain and nerves, eyes, and irner ear). The SLS-1 was launched aboard the Space Shuttle Orbiter Columbia (STS-40) on June 5, 1995.

TRPV5-mediated Ca2+ Reabsorption and Hypercalciuria

NASA Astrophysics Data System (ADS)

Renkema, Kirsten Y.; Hoenderop, Joost G. J.; Bindels, René J. M.

2007-04-01

The concerted action of the intestine, kidney and bone results in the maintenance of a normal Ca2+ balance, a mechanism that is tightly controlled by the calciotropic hormones vitamin D, parathyroid hormone and calcitonin. Disturbances in the Ca2+ balance have been linked to diverse pathophysiological disorders like urolithiasis, hypertension, electroencephalogram abnormalities and rickets. Importantly, the final amount of Ca2+ that is released from the body is determined in the distal part of the nephron, where active Ca2+ reabsorption occurs. Here, Transient Receptor Potential Vanilloid member 5 (TRPV5), a highly Ca2+-selective channel, has been recognized as the gatekeeper of active Ca2+ reabsorption. The in vivo relevance of TRPV5 has been further investigated by the characterization of TRPV5 knockout (TRPV5-/-) mice, which exhibit severe disturbances in renal Ca2+ handling, such as profound hypercalciuria, intestinal Ca2+ hyperabsorption and reduced bone thickness. Hypercalciuria increases the risk of kidney stone formation in these mice. This review highlights our current knowledge about TRPV5-mediated Ca2+ reabsorption and emphasizes the physiological relevance and the clinical implications related to the TRPV5-/- mice model.

Proposed biokinetic model for phosphorus

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

Leggett, Richard Wayne

2014-06-04

This paper reviews data related to the biokinetics of phosphorus in the human body and proposes a biokinetic model for systemic phosphorus for use in updated International Commission on Radiological Protection (ICRP) guidance on occupational intake of radionuclides. Compared with the ICRP s current occupational model for phosphorus (Publication 68, 1994) the proposed model provides a more realistic description of the paths of movement of phosphorus in the body and improved consistency with experimental, medical, and environmental data on the time-dependent distribution and retention of phosphorus following uptake to blood. For acute uptake of 32P to blood, the proposed modelmore » yields roughly a 50% decrease in dose estimates for bone surface and red marrow and a 6-fold increase in estimates for liver and kidney compared with the biokinetic model of Publication 68 (applying Publication 68 dosimetric models in both sets of calculations). For acute uptake of 33P to blood, the proposed model yields roughly a 50% increase in dose estimates for bone surface and red marrow and a 7-fold increase in estimates for liver and kidney compared with the model of Publication 68.« less

[Hypercalciuria].

PubMed

Périmenis, P; Wémeau, J-L; Vantyghem, M-C

2005-12-01

The frequency of hypercalciuria is increasing in western countries with an incidence of nephrolithiasis which can reach 13%. Hypercalciuria appears as an alteration of the calcium transport system (kidney, bowel, bone) which is regulated by calcitriol and parathormone. The aim of this review was to screen etiologies of hypercalciuria taking into account recent genetic advances (calcium epithelial channel and calcium sensing receptor). Hypercalciuria may be favored by nutritional causes (diet rich in calcium, sodium, carbohydrates, proteins, poor in phosphates and potassium). It may also be related to an increase in calcium absorption (vitamin D excess, primary hyperparathyroidism, sarcoidosis, lymphoma, estrogens, and certain genetic causes), an increase in osteoresorption (bone metastasis, myeloma, Paget, hyperthyroidism, immobilization, hypercortisolism and corticosteroid therapy), or a decrease of kidney tubular resorption (diuretics, Cacci and Ricci, acromegally, Bartter, familial dominant hypocalcemia, Fanconi, Dent, familial hypomagnesemia-hypercalciuria syndrome, type 1 distal tubular acidosis, pseudohypoaldosteronism, diabetes). If no cause is identified, persistence of hypercalciuria after instituting a correct diet is defined as idiopathic hypercalciuria. Treatment of the cause is essential in secondary hypercalciuria, in addition to diet (low sodium intake, normocalcic diet, hydration), associated with thiazide diuretics and biphosphonates if necessary.

Bone microarchitecture is more severely affected in patients on hemodialysis than in those receiving peritoneal dialysis.

PubMed

Pelletier, Solenne; Vilayphiou, Nicolas; Boutroy, Stéphanie; Bacchetta, Justine; Sornay-Rendu, Elisabeth; Szulc, Pawel; Arkouche, Walid; Guebre-Egziabher, Fitsum; Fouque, Denis; Chapurlat, Roland

2012-09-01

We used high-resolution quantitative computed tomography to study the microarchitecture of bone in patients with chronic kidney disease on dialysis. We compared bone characteristics in 56 maintenance hemodialysis (21 women, 14 post-menopausal) and 23 peritoneal dialysis patients (9 women, 6 post-menopausal) to 79 healthy men and women from two cohorts matched for age, body mass index, gender, and menopausal status. All underwent dual-energy X-ray absorptiometry of the spine and hip to measure areal bone mineral density, and high-resolution peripheral quantitative computed tomography of the radius and tibia to measure volumetric bone mineral density and microarchitecture. When compared to their matched healthy controls, patients receiving hemodialysis and peritoneal dialysis had a significantly lower areal bone mineral density in the hip. Hemodialysis patients had significantly lower total, cortical, and trabecular volumetric bone mineral density at both sites. Hemodialysis patients had significantly lower trabecular volumetric bone mineral density and microarchitecture at the tibia than the peritoneal dialysis patients. Overall, peritoneal dialysis patients were less affected, their cortical thickness at the distal tibia being the only significant difference versus controls. Thus, we found more severe trabecular damage at the weight-bearing tibia in hemodialysis compared to peritoneal dialysis patients, but this latter finding needs confirmation in larger cohorts.

A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology.

PubMed

Gianfranca, Cabiddu; Donatella, Spotti; Giuseppe, Gernone; Domenico, Santoro; Gabriella, Moroni; Gina, Gregorini; Franca, Giacchino; Rossella, Attini; Monica, Limardo; Linda, Gammaro; Tullia, Todros; Piccoli, Giorgina Barbara

2018-06-14

Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes "normal" or "good" kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1-2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage "non-ideal" situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial "third element".

Cardiorenal Syndrome: New Developments in the Understanding and Pharmacologic Management

PubMed Central

2013-01-01

Summary Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research. PMID:23929925

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

PubMed

Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

Comparison of Recipient Outcomes After Kidney Transplantation: In-House Versus Imported Deceased Donors.

PubMed

Lim, S Y; Gwon, J G; Kim, M G; Jung, C W

2018-05-01

Increased cold ischemia time in cadaveric kidney transplants has been associated with a high rate of delayed graft function (DGF), and even with graft survival. Kidney transplantation using in-house donors reduces cold preservation time. The purpose of this study was to compare the clinical outcomes after transplantation in house and externally. We retrospectively reviewed the medical records of donors and recipients of 135 deceased-donor kidney transplantations performed in our center from March 2009 to March 2016. Among the 135 deceased donors, 88 (65.2%) received the kidneys from in-house donors. Median cold ischemia time of transplantation from in-house donors was shorter than for imported donors (180.00 vs 300.00 min; P < .001). The risks of DGF and slow graft function were increased among the imported versus in-house donors. Imported kidney was independently associated with greater odds of DGF in multivariate regression analysis (odds ratio, 4.165; P = .038). However, the renal function of recipients at 1, 3, 5, and 7 years after transplantation was not significantly different between the 2 groups. Transplantation with in-house donor kidneys was significantly associated with a decreased incidence of DGF, but long-term graft function and survival were similar compared with imported donor kidneys. Copyright © 2018 Elsevier Inc. All rights reserved.

Red Kidney: Kidney Transplant From a Deceased Donor Who Received Massive Blood Transfusion During Cardiopulmonary Bypass.

PubMed

Bell, Richard; Hanif, Faisal; Prasad, Padmini; Ahmad, Niaz

2016-06-01

Here, we present a case of a deceased-donor kidney transplant. The brain-dead donor had received a massive blood transfusion during cardiopulmonary bypass, which lead to hemolysis, hemoglobinuria, acute kidney injury, and renal replacement therapy. The kidney appeared red after in situ flush. Postoperatively, the recipient developed delayed graft function. Protocol biopsy during the postoperative period revealed the widespread deposition of heme pigment in the renal tubules. Massive blood transfusion and cardiopulmonary bypass surgery are associated with hemolysis and heme pigment deposition in the renal tubules, which subsequently lead to acute kidney injury. Kidneys from such donors appear red and, while this does not preclude transplant, are likely to develop delayed graft function.

Stem cells in kidney regeneration.

PubMed

Yokote, Shinya; Yokoo, Takashi

2012-01-01

Currently many efforts are being made to apply regenerative medicine to kidney diseases using several types of stem/progenitor cells, such as mesenchymal stem cells, renal stem/progenitor cells, embryonic stem cells and induced pluripotent stem cells. Stem cells have the ability to repair injured organs and ameliorate damaged function. The strategy for kidney tissue repair is the recruitment of stem cells and soluble reparative factors to the kidney to elicit tissue repair and the induction of dedifferentiation of resident renal cells. On the other hand, where renal structure is totally disrupted, absolute kidney organ regeneration is needed to rebuild a whole functional kidney. In this review, we describe current advances in stem cell research for kidney tissue repair and de novo organ regeneration.

Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

PubMed

Molnar, Amber O; Eddeen, Anan Bader; Ducharme, Robin; Garg, Amit X; Harel, Ziv; McCallum, Megan K; Perl, Jeffrey; Wald, Ron; Zimmerman, Deborah; Sood, Manish M

2017-07-06

Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function. Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF ( P <0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses. Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

An unusual case of acute kidney injury due to vancomycin lessons learnt from reliance on eGFR.

PubMed

Barraclough, Katherine; Harris, Marianne; Montessori, Val; Levin, Adeera

2007-08-01

We present a case of renal impairment in an emaciated HIV-infected male that initially went unrecognized because of reliance on serum creatinine and estimated glomerular filtration rate (eGFR). Inaccurate vancomycin dosing led to toxic drug levels (66 mg/l), associated with acute and severe worsening of kidney function. This occurred in the context of escalating doses of vancomycin given in the presence of changing kidney function, albeit kidney function that always remained well within the normal range (serum creatinine 29 - 42 mumol/l). In the absence of other plausible explanations, a presumptive diagnosis of vancomycin nephrotoxicity was made. Given the rarity of this diagnosis in the current era, we discuss the pathophysiology of vancomycin nephrotoxicity. We also explore the potential reasons for inaccuracy of GFR prediction equations in the HIV population, and discuss the potential pitfalls associated with application of eGFR or even serum creatinine without appropriate understanding of their limitations. We believe our case highlights a number of important teaching points: Vancomycin nephrotoxitiy is rare but can occur in the setting of kidney dysfunction. Current assessment of kidney function using creatinine and eGFR requires awareness of the clinical caveats in which these measures may be misleading. Acute changes in kidney function, irrespective of the test used, should be contextualized to the individual situation. Persons with HIV and low muscle mass constitute a specific subgroup in whom assessment of kidney function may be problematic using creatinine. We support ongoing efforts to develop or refine equations for specific unique and easily identifiable populations.

The Impact of the Nitric Oxide (NO)/Soluble Guanylyl Cyclase (sGC) Signaling Cascade on Kidney Health and Disease: A Preclinical Perspective.

PubMed

Krishnan, Shalini M; Kraehling, Jan R; Eitner, Frank; Bénardeau, Agnès; Sandner, Peter

2018-06-09

Chronic Kidney Disease (CKD) is a highly prevalent disease with a substantial medical need for new and more efficacious treatments. The Nitric Oxide (NO), soluble guanylyl cyclase (sGC), cyclic guanosine monophosphate (cGMP) signaling cascade regulates various kidney functions. cGMP directly influences renal blood flow, renin secretion, glomerular function, and tubular exchange processes. Downregulation of NO/sGC/cGMP signaling results in severe kidney pathologies such as CKD. Therefore, treatment strategies aiming to maintain or increase cGMP might have beneficial effects for the treatment of progressive kidney diseases. Within this article, we review the NO/sGC/cGMP signaling cascade and its major pharmacological intervention sites. We specifically focus on the currently known effects of cGMP on kidney function parameters. Finally, we summarize the preclinical evidence for kidney protective effects of NO-donors, PDE inhibitors, sGC stimulators, and sGC activators.

Kidney Calculi: Pathophysiology and as a Systemic Disorder.

PubMed

Shadman, Arash; Bastani, Bahar

2017-05-01

The pathophysiology of urinary stone formation is complex, involving a combination of metabolic, genetic, and environmental factors. Over the past decades, remarkable advances have been emerged in the understanding of the pathogenesis, diagnosis, and treatment of calcium kidney calculi. For this review, both original and review articles were found via PubMed search on pathophysiology, diagnosis, and management of urinary calculi. These resources were integrated with the authors' knowledge of the field. Nephrolithiasis is suggested to be associated with systemic disorders, including chronic kidney insufficiency, hematologic malignancies, endocrine disorders, autoimmune diseases, inflammatory bowel diseases, bone loss and fractures, hypertension, type 2 diabetes mellitus, metabolic syndrome, and vascular diseases like coronary heart diseases and most recently ischemic strokes. This is changing the perspective of nephrolithiasis from an isolated disorder to a systemic disease that justifies further research in understanding the underlying mechanisms and elaborating diagnostic-therapeutic options.

[Kidney function and liver transplantation].

PubMed

Gámán, György; Gelley, Fanni; Gerlei, Zsuzsa; Dabasi, Eszter; Görög, Dénes; Fehérvári, Imre; Kóbori, László; Lengyel, Gabriella; Zádori, Gergely; Fazakas, János; Doros, Attila; Sárváry, Enikő; Nemes, Balázs

2013-06-30

In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. Retrospective data analysis was performed after primary liver transplantations (n = 319). impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). Selection of personalized immunosuppressive medication has a positive effect on renal function.

Calcium Balance in Chronic Kidney Disease.

PubMed

Hill Gallant, Kathleen M; Spiegel, David M

2017-06-01

The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Does size matter? Kidney transplant donor size determines kidney function among living donors

PubMed Central

Narasimhamurthy, Meenakshi; Smith, Lachlan M.; Machan, Jason T.; Reinert, Steven E.; Gohh, Reginald Y.; Dworkin, Lance D.; Merhi, Basma; Patel, Nikunjkumar; Beland, Michael D.

2017-01-01

Background Kidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined. Methods We examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data. Results Donors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 over a median 24-month follow-up than those with smaller cortical volumes (P <0.001), had a shorter duration of renal recovery (1.3–2.2 versus 32.5 days) and started with a higher eGFR at pre-donation (107–110 versus 91 mL/min/1.73 m2) and immediately post-nephrectomy (∼63 versus 50–51 mL/min/1.73 m2). Similar findings were seen with adjusted total volume and length. Conclusions Larger kidney donors were more likely to achieve an eGFR ≥60 mL/min/1.73 m2 with renal recovery over a shorter duration due to higher pre-donation and initial post-nephrectomy eGFRs. PMID:28638611

Chronic Kidney Disease Epidemiology Collaboration versus Modification of Diet in Renal Disease equations for renal function evaluation in patients undergoing partial nephrectomy.

PubMed

Shikanov, Sergey; Clark, Melanie A; Raman, Jay D; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Huang, William C; Shalhav, Arieh L; Eggener, Scott E

2010-11-01

A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy. We assembled a cohort of 1,158 patients from 5 institutions who underwent partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] × 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations. Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was -12% for both equations (p = 0.2). The proportion of patients with newly developed chronic kidney disease stage III following surgery was 32% and 25%, according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, respectively (p = 0.001). For patients with 2 functioning kidneys undergoing partial nephrectomy the Chronic Kidney Disease Epidemiology Collaboration equation provides slightly higher glomerular filtration rate estimates compared to the Modification of Diet in Renal Disease equation, with 7% fewer patients categorized as having chronic kidney disease stage III or worse. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Primary hyperparathyroidism: recent advances.

PubMed

Walker, Marcella D; Bilezikian, John P

2018-07-01

The purpose of this review is to describe recent advances and changes in the evaluation and management of primary hyperparathyroidism (PHPT). Although it has long been recognized that asymptomatic PHPT is associated with bone loss, particularly at cortical skeletal sites when evaluated with dual-energy X-ray absorptiometry, new imaging techniques suggest that trabecular skeletal deterioration as well as clinically silent vertebral fractures and nephrolithiasis are common. Nonclassical targets of asymptomatic PHPT as well as the effect of vitamin D deficiency and treatment upon PHPT presentation have been the subject of recent intense investigation. Randomized clinical trials are now available regarding the effect of parathyroidectomy (PTX) upon both classical and nonclassical target organs. They have confirmed results from observational studies with regard to the skeletal benefits of PTX but have not consistently shown improvements in nonclassical symptoms. These findings have led to recommendations for more extensive renal and skeletal evaluation and broader criteria for PTX in PHPT. In addition to dual-energy X-ray absorptiometry, vertebral and renal imaging is recommended. When available, trabecular imaging techniques may be helpful. PTX criteria now include subclinical kidney stones, vertebral fractures and hypercalciuria, in addition to those based on age, serum calcium, bone densitometry and renal function.

Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention.

PubMed

Mugwanya, Kenneth K; Baeten, Jared M

2016-01-01

Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP's substantial reduction in the risk of HIV infection.

Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study.

PubMed

Yin, Zhaoxue; Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Song, Aiqin; Feng, Lei; Qiu, Chengxuan

2016-01-12

The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. This cross-sectional study included 1,358 participants (age ≥60 years; 60.5% women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) <60 ml/min/1.73 m(2). Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Cognitive impairment was defined in 197 (14.5%) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was -0.06 (95% confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFRcys <60, 60-89.9, and ≥90 ml/min/1.73 m(2) were -0.15 (-0.28, -0.02), -0.01 (-0.10, 0.08), and 0 (reference) (Ptrend = 0.046), respectively. Diabetes and impaired kidney function showed an interactive effect on cognitive impairment ( interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95% CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

Prevention of Lethal Murine Hypophosphatasia by Neonatal Ex Vivo Gene Therapy Using Lentivirally Transduced Bone Marrow Cells.

PubMed

Iijima, Osamu; Miyake, Koichi; Watanabe, Atsushi; Miyake, Noriko; Igarashi, Tsutomu; Kanokoda, Chizu; Nakamura-Takahashi, Aki; Kinoshita, Hideaki; Noguchi, Taku; Abe, Shinichi; Narisawa, Sonoko; Millán, José Luis; Okada, Takashi; Shimada, Takashi

2015-12-01

Hypophosphatasia (HPP) is an inherited skeletal and dental disease caused by loss-of-function mutations in the gene that encodes tissue-nonspecific alkaline phosphatase (TNALP). The major symptoms of severe forms of the disease are bone defects, respiratory insufficiency, and epileptic seizures. In 2015, enzyme replacement therapy (ERT) using recombinant bone-targeted TNALP with deca-aspartate (D10) motif was approved to treat pediatric HPP patients in Japan, Canada, and Europe. However, the ERT requires repeated subcutaneous administration of the enzyme because of the short half-life in serum. In the present study, we evaluated the feasibility of neonatal ex vivo gene therapy in TNALP knockout (Akp2(-/-)) HPP mice using lentivirally transduced bone marrow cells (BMC) expressing bone-targeted TNALP in which a D10 sequence was linked to the C-terminus of soluble TNALP (TNALP-D10). The Akp2(-/-) mice usually die within 20 days because of growth failure, epileptic seizures, and hypomineralization. However, an intravenous transplantation of BMC expressing TNALP-D10 (ALP-BMC) into neonatal Akp2(-/-) mice prolonged survival of the mice with improved bone mineralization compared with untransduced BMC-transplanted Akp2(-/-) mice. The treated Akp2(-/-) mice were normal in appearance and experienced no seizures during the experimental period. The lentivirally transduced BMC were efficiently engrafted in the recipient mice and supplied TNALP-D10 continuously at a therapeutic level for at least 3 months. Moreover, TNALP-D10 overexpression did not affect multilineage reconstitution in the recipient mice. The plasma ALP activity was sustained at high levels in the treated mice, and tissue ALP activity was selectively detected on bone surfaces, not in the kidneys or other organs. No ectopic calcification was observed in the ALP-BMC-treated mice. These results indicate that lentivirally transduced BMC can serve as a reservoir for stem cell-based ERT to rescue the Akp2(-/-) phenotype. Neonatal ex vivo gene therapy thus appears to be a possible treatment option for treating severe HPP.

Prevention of Lethal Murine Hypophosphatasia by Neonatal Ex Vivo Gene Therapy Using Lentivirally Transduced Bone Marrow Cells

PubMed Central

Iijima, Osamu; Miyake, Koichi; Watanabe, Atsushi; Miyake, Noriko; Igarashi, Tsutomu; Kanokoda, Chizu; Nakamura-Takahashi, Aki; Kinoshita, Hideaki; Noguchi, Taku; Abe, Shinichi; Narisawa, Sonoko; Millán, José Luis; Okada, Takashi; Shimada, Takashi

2015-01-01

Hypophosphatasia (HPP) is an inherited skeletal and dental disease caused by loss-of-function mutations in the gene that encodes tissue-nonspecific alkaline phosphatase (TNALP). The major symptoms of severe forms of the disease are bone defects, respiratory insufficiency, and epileptic seizures. In 2015, enzyme replacement therapy (ERT) using recombinant bone-targeted TNALP with deca-aspartate (D10) motif was approved to treat pediatric HPP patients in Japan, Canada, and Europe. However, the ERT requires repeated subcutaneous administration of the enzyme because of the short half-life in serum. In the present study, we evaluated the feasibility of neonatal ex vivo gene therapy in TNALP knockout (Akp2−/−) HPP mice using lentivirally transduced bone marrow cells (BMC) expressing bone-targeted TNALP in which a D10 sequence was linked to the C-terminus of soluble TNALP (TNALP-D10). The Akp2−/− mice usually die within 20 days because of growth failure, epileptic seizures, and hypomineralization. However, an intravenous transplantation of BMC expressing TNALP-D10 (ALP-BMC) into neonatal Akp2−/− mice prolonged survival of the mice with improved bone mineralization compared with untransduced BMC-transplanted Akp2−/− mice. The treated Akp2−/− mice were normal in appearance and experienced no seizures during the experimental period. The lentivirally transduced BMC were efficiently engrafted in the recipient mice and supplied TNALP-D10 continuously at a therapeutic level for at least 3 months. Moreover, TNALP-D10 overexpression did not affect multilineage reconstitution in the recipient mice. The plasma ALP activity was sustained at high levels in the treated mice, and tissue ALP activity was selectively detected on bone surfaces, not in the kidneys or other organs. No ectopic calcification was observed in the ALP-BMC-treated mice. These results indicate that lentivirally transduced BMC can serve as a reservoir for stem cell-based ERT to rescue the Akp2−/− phenotype. Neonatal ex vivo gene therapy thus appears to be a possible treatment option for treating severe HPP. PMID:26467745

Kidney function endpoints in kidney transplant trials: a struggle for power.

PubMed

Ibrahim, A; Garg, A X; Knoll, G A; Akbari, A; White, C A

2013-03-01

Kidney function endpoints are commonly used in randomized controlled trials (RCTs) in kidney transplantation (KTx). We conducted this study to estimate the proportion of ongoing RCTs with kidney function endpoints in KTx where the proposed sample size is large enough to detect meaningful differences in glomerular filtration rate (GFR) with adequate statistical power. RCTs were retrieved using the key word "kidney transplantation" from the National Institute of Health online clinical trial registry. Included trials had at least one measure of kidney function tracked for at least 1 month after transplant. We determined the proportion of two-arm parallel trials that had sufficient sample sizes to detect a minimum 5, 7.5 and 10 mL/min difference in GFR between arms. Fifty RCTs met inclusion criteria. Only 7% of the trials were above a sample size of 562, the number needed to detect a minimum 5 mL/min difference between the groups should one exist (assumptions: α = 0.05; power = 80%, 10% loss to follow-up, common standard deviation of 20 mL/min). The result increased modestly to 36% of trials when a minimum 10 mL/min difference was considered. Only a minority of ongoing trials have adequate statistical power to detect between-group differences in kidney function using conventional sample size estimating parameters. For this reason, some potentially effective interventions which ultimately could benefit patients may be abandoned from future assessment. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Outcome of organs procured from donors on extracorporeal membrane oxygenation support: an analysis of kidney and liver allograft data.

PubMed

Carter, Timothy; Bodzin, Adam S; Hirose, Hitoshi; West, Sharon; Hasz, Richard; Maley, Warren R; Cavarocchi, Nicholas C

2014-07-01

Extracorporeal membrane oxygenation has become rescue therapy for adults with overwhelming cardiac and/or respiratory failure. Not all patients are saved, creating a new cohort of potential organ donors. This study examines the outcomes of liver and kidney allografts procured from donors on extracorporeal membrane oxygenation (ECMO). A retrospective review was conducted through the local organ procurement organization. Donors on ECMO prior to notification were classified into donation after brain death (DBD) and donation after cardiac death (DCD). We compared short-term outcome data against published standards. Between 1995 and 2012, 97 organs were procured from 41 donors supported on ECMO. There were 68 kidneys donated, 51 were transplanted and 17 discarded. Excluding extended criteria donors, 29 DBD and 13 DCD kidneys were transplanted from donors supported on ECMO. Delayed graft function occurred in 34% of DBD kidneys and 38% of DCD kidneys. Kidney allograft survival at one yr was 93%. Twenty-four livers were procured, nine discarded, and 15 transplanted. Ninety-three percent of liver transplant recipients were alive with graft function at one yr. Donation after brain death kidneys procured from donors on ECMO perform similarly to non-ECMO organs with regard to delayed graft function (DGF), one-yr graft survival and function. Livers from ECMO donors have a higher discard rate than non-ECMO donors, but function similarly at six months and one yr. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Silent ureteral stones: impact on kidney function--can treatment of silent ureteral stones preserve kidney function?

PubMed

Marchini, Giovanni S; Vicentini, Fabio C; Mazzucchi, Eduardo; Brito, Arthur; Ebaid, Gustavo; Srougi, Miguel

2012-02-01

To report our experience with silent ureteral stones and expose their true influence on renal function. We analyzed 506 patients who had undergone ureterolithotripsy from January 2005 to May 2010. Silent ureteral stones were calculi found in the absence of any specific or subjective ureteral stone-related symptoms. Of the 506 patients, 27 (5.3%) met these criteria (global cohort). All patients were assessed postoperatively with dimercaptosuccinic acid scintigraphy (DMSA). A difference in relative kidney function of >10% was considered abnormal. Pre- and postoperative comparative DMSA analyses were electively obtained for 9 patients (kidney function cohort). A t test was used to assess the numeric variables, and the chi-square test or Fisher's exact test was used for categorical variables. Two-tailed P<.05 was considered statistically significant. Stones were diagnosed by radiologic abdominal evaluation for nonurologic diseases in 40% and after previous nephrolithiasis treatment in 33%. The primary therapy was ureterolithotripsy in 88%. The mean follow-up time was 23 months. The overall ureteral stone-free rate after 1 and 2 procedures was 96% and 100%, respectively. In the global cohort, the mean pre- and postoperative serum creatinine levels were similar (P=.39), and the mean postoperative function on DMSA was 31%. In the kidney function cohort, no difference was found between the pre- and postoperative DMSA findings (22%±12.1% vs 20%±11.8%; P=.83) and serum creatinine (0.8±0.13 mg/dL vs 1.0±0.21 mg/dL; P=.45). Silent ureteral stones are associated with decreased kidney function present at the diagnosis. Hydronephrosis tends to diminish after stone removal, and kidney function remains unaltered. Copyright © 2012 Elsevier Inc. All rights reserved.

Long-term Effects of Off-Pump Coronary Bypass Versus Conventional Coronary Bypass Grafting on Renal Function.

PubMed

Hynes, Conor F; Colo, Sanchez; Amdur, Richard L; Chawla, Lakhmir S; Greenberg, Michael D; Trachiotis, Gregory D

2016-01-01

This study aimed to evaluate the short- and long-term effects of conventional on-pump coronary bypass grafting (cCABG) compared with off-pump coronary artery bypass (OPCAB) on renal function. A retrospective review of patients undergoing coronary bypass grafting from 2004 through 2013 at a single center was conducted. Preoperative renal function, perioperative acute kidney injury, and long-term glomerular filtration were evaluated. Multivariable analyses were used to determine factors contributing to short- and long-term renal impairment. A total of 234 patients underwent cCABG, and 582 underwent OPCAB. Patients undergoing OPCAB were significantly older, had greater preoperative renal dysfunction, had greater functional dependence, and took more hypertension medications. Multivariable analyses found that 30-day acute kidney injury was an independent risk factor for a 10% decline in glomerular filtration rate at 1 and 5 years (P < 0.0001 and 0.002, respectively). However, the use of cardiopulmonary bypass was not found to influence long-term renal function (P = 0.78 at 1 year, P = 0.76 at 5 years). The percentage of patients experiencing a 10% drop in renal function from baseline at 1 year (33% OPCAB, 35% cCABG; P = 0.73) and 5 years (16% OPCAB, 16% cCABG; P = 0.93) were not significantly different. Independent predictors of acute kidney injury included baseline kidney function (P = 0.04) and age (P < 0.0001), whereas cardiopulmonary bypass did not affect the incidence (P = 0.17). A propensity-matched analysis confirmed these findings. Acute kidney injury is a risk factor for long-term renal dysfunction after either bypass method and was not greater after cCABG compared with OPCAB. Patients undergoing OPCAB did not experience greater decrease in long-term kidney function despite having worse baseline kidney function.

Calcium as a cardiovascular toxin in CKD-MBD.

PubMed

Moe, Sharon M

2017-07-01

Disordered calcium balance and homeostasis are common in patients with chronic kidney disease. Such alterations are commonly associated with abnormal bone remodeling, directly and indirectly. Similarly, positive calcium balance may also be a factor in the pathogenesis of extra skeletal soft tissue and arterial calcification. Calcium may directly affect cardiac structure and function through direct effects to alter cell signaling due to abnormal intracellular calcium homeostasis 2) extra-skeletal deposition of calcium and phosphate in the myocardium and small cardiac arterioles, 3) inducing cardiomyocyte hypertrophy through calcium and hormone activation of NFAT signaling mechanisms, and 4) increased aorta calcification resulting in chronic increased afterload leading to hypertrophy. Similarly, calcium may alter vascular smooth muscle cell function and affect cell signaling which may predispose to a proliferative phenotype important in arteriosclerosis and arterial calcification. Thus, disorders of calcium balance and homeostasis due to CKD-MBD may play a role in the high cardiovascular burden observed in patients with CKD. Published by Elsevier Inc.