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Sample records for kidney function bone

  1. [Chronic Kidney Disease and Bone].

    PubMed

    James, Junichiro

    2016-08-01

    Both bone and kidney are members of the physiological network sharing a purpose of systemic mineral metabolism. In patients with chronic kidney disease whose kidney function is lost, the organ functions of other mineral metabolism network member including bone fail into uncontrollable due to dysregulated feedback system. This is the concept of Chronic Kidney Disease(related)- Mineral and Bone Disorder(CKD-MBD). However, the bone metabolic abnormalities in patients with chronic kidney disease cannot be explained merely by the framework of this mineral metabolism network. Although dialysis patients show several times higher hip fracture risk than general population, the main pathogenesis seems not to be their disordered mineral metabolism. We need to consider "uremic osteoporosis" characterized by deteriorated bone material properties due to uremic condition.

  2. Effects of Dietary Calcium Supplementation on Bone Metabolism, Kidney Mineral Concentrations, and Kidney Function in Rats Fed a High-Phosphorus Diet.

    PubMed

    Katsumata, Shinichi; Matsuzaki, Hiroshi; Uehara, Mariko; Suzuki, Kazuharu

    2015-01-01

    We investigated the effects of dietary calcium (Ca) supplementation on bone metabolism, kidney mineral concentrations, and kidney function in rats fed a high-phosphorus (P) diet. Wistar strain rats were randomly divided into 4 dietary groups and fed their respective diets for 21 d: a diet containing 0.3% P and 0.5% Ca (C), a diet containing 1.5% P and 0.5% Ca (HP), a diet containing 0.3% P and 1.0% Ca (HCa), or a diet containing 1.5% P and 1.0% Ca (HPCa). Compared to the C group, the high-P diet increased serum parathyroid hormone concentration, markers of bone turnover, receptor activator of NF-κB ligand mRNA expression of the femur, kidney Ca and P concentrations, urinary N-acetyl-β-D-glucosaminidase activity, and urinary β2-microglobulin excretion, and decreased bone mineral content and bone mineral density of the femur and tibia. Dietary Ca supplementation improved the parameters of bone metabolism and kidney function in rats fed the high-P diet, while there were no significant differences in kidney Ca or P concentrations between the HP and HPCa groups. These results suggest that dietary Ca supplementation prevented the bone loss and decline in kidney function induced by a high-P diet, whereas dietary Ca supplementation did not affect kidney mineral concentrations in rats fed the high-P diet.

  3. Bone Disease after Kidney Transplantation

    PubMed Central

    Bouquegneau, Antoine; Salam, Syrazah; Delanaye, Pierre; Eastell, Richard

    2016-01-01

    Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high– or low–turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients. PMID:26912549

  4. Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.

    PubMed

    Yang, Chao; Kwak, Lucia; Ballew, Shoshana H; Garimella, Pranav S; Jaar, Bernard G; Folsom, Aaron R; Heiss, Gerardo; Selvin, Elizabeth; Lutsey, Pamela L; Coresh, Josef; Matsushita, Kunihiro

    2017-09-22

    Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m(2)). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD. Copyright © 2017

  5. Bone marrow Ly6Chigh monocytes are selectively recruited to injured kidney and differentiate into functionally distinct populations.

    PubMed

    Lin, Shuei Liong; Castaño, Ana P; Nowlin, Brian T; Lupher, Mark L; Duffield, Jeremy S

    2009-11-15

    Roles for monocyte/macrophages (Mphi) in directing the development of tissue fibrosis are increasingly recognized. Macrophages form a heterogeneous group of inflammatory leukocytes, and the mechanisms by which they acquire heterogeneity and its functional significance are unclear. We used the unilateral ureteral obstruction model of progressive kidney fibrosis to explore macrophage heterogeneity and function further. Unilateral ureteral obstruction kidney Mphis form three distinct subpopulations defined by the marker Ly6C, all of which are derived from a single Ly6C(high) bone marrow monocyte population selectively recruited to the kidney. Conditional ablation of these Mphis in vivo in CD11b-DTR mice is potently antifibrotic. The mRNA transcription profile of these populations is consistent with differential functional roles for each subpopulation, with Ly6C(low) macrophages transcribing genes consistent with selective profibrotic or M2-type function. Furthermore, bone marrow chimerism studies indicate that although resident kidney macrophages proliferate markedly to comprise up to 40% of the inflammatory macrophage population, they do not contribute to fibrosis. Our data identify Ly6C as a marker of functionally discrete tissue macrophage subsets and support a model of selective recruitment of Ly6C(high) bone marrow monocytes to the kidney that differentiate into three populations of kidney macrophages, including a profibrotic Ly6C(low) population.

  6. Diffuse renal parenchyma uptake with bone scintigraphy in a patient with paroxysmal nocturnal hemoglobinuria and normal kidney function.

    PubMed

    Balink, Hans; Hoogendoorn, Mels; Hemmelder, Marc

    2014-03-01

    A 41-year-old woman with a Harrington spondylodesis presented with lower back pain. Bone scintigraphy showed diffusely increased parenchymal uptake in both kidneys. She reported 2 previous periods of dark, almost black, urine. Additional flow cytometric analysis confirmed the diagnosis of paroxysmal nocturnal hemoglobinuria. The increased renal parenchyma uptake is very probably due to paroxysmal nocturnal hemoglobinuria-related renal hemosiderosis. Remarkably, the patient did not develop any abnormality of renal function.

  7. 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, ...

  8. Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease

    PubMed Central

    Iwasaki, Yoshiko; Kazama, Junichiro James

    2017-01-01

    Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis. There are many uremia-associated factors that contribute to bone fragility, including severe secondary hyperparathyroidism, skeletal resistance to parathyroid hormone, and bone mineralization disorders. Uremia also aggravates bone volume loss, disarranges microarchitecture, and increases the deterioration of material properties of bone through abnormal bone cells or excess oxidative stress. In this review, we outline the prevalence of fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and discuss possible factors that exacerbate the mechanical properties of bone. PMID:28421193

  9. [Bone turnover and mineralization in patients with kidney failure].

    PubMed

    James, Junichiro

    2016-09-01

    Bone remodeling is a device to accomplish "the buffering of the extracellular fluid mineral", which is one of the two major physiological functions of bone. Bone turnover is a term to express the frequency of bone remodeling, and its last step is calcification. When remodeling is induced, at first a large amount of mineral is released from bone to extracellular fluid transiently, and thereafter mineral is slowly and steadily drawn into bone. The extracellular minerals, especially calcium, are maintained by this repetition. When kidney is injured, bone turnover takes a wide spectrum from remarkably high cases to low cases. Primary calcification also shows marked individual differences. The classic renal bone diseases 5 classification clearly categorizes these disease condition, which is synonymous with renal osteodystrophy today.

  10. Effect of kidney transplantation on bone.

    PubMed

    Kodras, K; Haas, M

    2006-08-01

    A broad range of different factors aggravates renal osteodystrophy, which is present in virtually all patients with chronic kidney disease and after successful kidney transplantation. Altered hormonal status, including sex hormones and parathyroid hormone (PTH), a deficit of 1,25(OH)(2) vitamin D(3) (calcitriol), immunosuppressive therapy and post-operative immobilization contribute to a progressive loss of bone density and structure. The decrease of bone mass is particularly prominent during the first 6 months after kidney transplantation and is associated with an increased number of fractures, both compared with the normal population as well as with dialysis patients. At particular risk are patients with a history of diabetes, long duration of haemodialysis and post-menopausal women. To prevent post-transplant bone loss prescription of steroids should be minimized and withdrawn as early as possible. Additional intake of alpha-calcidol [25(OH) vitamin D(3)] or calcitriol, despite normal serum levels, reduces persistent hyperparathyroidism after kidney transplantation, improves intestinal calcium absorption and activates osteoblasts. Inhibition of osteoclasts by biphosphonate therapy seems to effectively reverse bone loss during the early and late course of kidney transplantation. However, as the majority of transplant recipients have a low-turnover bone disease, inhibition of osteoclasts, through which bone turnover is impaired, might further reduce osteoblast activity and promote osteoid synthesis. Most investigations were small-scale studies with 10-100 participants and a follow up of only 12 months. This makes conclusions on the effect of any intervention on the fracture rate impossible. Larger, randomized multicentre studies investigating bone-sparing therapy on hard end points are therefore advocated.

  11. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    PubMed

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  12. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder

    PubMed Central

    Seifert, Michael E.; Hruska, Keith A.

    2015-01-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well, as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This Overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy. PMID:26356179

  13. 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

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

    2013-08-15

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. 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

    SciTech Connect

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

    2013-08-15

    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. -- 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.

  15. Ear length and kidney function decline after kidney donation.

    PubMed

    Katavetin, Pisut; Watanatorn, Salin; Townamchai, Natavudh; Avihingsanon, Yingyos; Praditpornsilpa, Kearkiat

    2016-11-01

    The preservation of kidney function after kidney donation depends on the kidney reserve - the potential of the remaining kidney to boost their function after loss of the other kidney. In Traditional Chinese Medicine, size and shape of the external ears are examined to evaluate the person's kidney health. We hypothesized that ear size might be a practical yet overlooked marker of kidney reserve. Fifty kidney transplantation donors were participated in this study. The length and width of both ears of all participants were measured during one of the post-donation visits. Pre-donation serum creatinine and post-donation serum creatinine as well as other relevant parameters (age, sex, weight, height, etc.) of the participants were extracted from medical records. The estimated GFR was calculated from serum creatinine, age and sex using the CKD-EPI equation. Ear length negatively associated with %GFR decline after kidney donation. For every 1 cm increase in ear length, it was associated with 5.7% less GFR decline after kidney donation (95% Confidence Interval 0.2 to 11.3, P = 0.04). Ear width, as well as age, sex, body weight, height, body mass index, and pre-donation eGFR did not significantly associate with the GFR decline. Our findings support the notion of Traditional Chinese Medicine that ear morphology may be associated with kidney health and suggest that ear length might be a useful predictor of kidney function decline after kidney donation.

  16. 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

  17. 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.

  18. CINACALCET IMPROVES BONE DENSITY IN POST KIDNEY TRANSPLANT HYPERPARATHYROIDISM

    PubMed Central

    Cho, ME; Duan, Z; Chamberlain, CE; Reynolds, JC; Ring, MS; Wright, EC; Mannon, RB

    2010-01-01

    The recent availability of cinacalcet has provided a possible alternative to parathyroidectomy in kidney transplant patients with persistent hyperparathyroidism, but its effect on bone mass density (BMD) is unknown. From our database containing 163 kidney transplants performed at our center from 1999-2007, we compared recipients who received cinacalcet for persistent hypercalcemia and hyperparathyroidism following renal tx (n=8; CIN) with up to 2 other post tx patients matched for age, sex, race, and graft function (n=15; CON). The outcome of the study was BMD changes from baseline to 12, 24, and 36 months post renal tx. Repeated Measures Mixed model was used to assess the difference of BMD change between two groups. Cinacalcet therapy was started at a median of 9 months (range; 1, 24 months) post tx with a mean dose 56±29 mg/d (mean duration; 1.6 years, range; 1, 2.1). Cinacalcet therapy was associated with significant reduction of serum calcium compared to control. Cinacalcet therapy was associated with greater BMD increase at the hip over the 36-month post transplant period. Cinacalcet was well tolerated. Our results suggest that cinacalcet may have a small but favorable effect on bone density following kidney transplantation. PMID:21094814

  19. Cinacalcet improves bone density in post-kidney transplant hyperparathyroidism.

    PubMed

    Cho, M E; Duan, Z; Chamberlain, C E; Reynolds, J C; Ring, M S; Mannon, R B

    2010-11-01

    The recent availability of cinacalcet has provided a possible alternative to parathyroidectomy in kidney transplant patients with persistent hyperparathyroidism, but its effect on bone mass density (BMD) is unknown. From our database containing 163 kidney transplants performed at our center from 1999 to 2007, we compared recipients who received cinacalcet for persistent hypercalcemia and hyperparathyroidism following renal transplantation (n = 8) with up to two other posttransplant patients matched for age, sex, race, and graft function (n = 15). The outcome of the study was BMD changes from baseline to 12, 24, and 36 months post-renal transplantation. Repeated-measures mixed model was used to assess the difference of BMD change between two groups. Cinacalcet therapy was started at a median of 9 (range = 1 to 24) months posttransplant with a mean dose 56 ± 29 mg/d (mean duration = 1.6; range = 1 to 2.1 years). Cinacalcet therapy was associated with significant reduction of serum calcium compared to control. Cinacalcet therapy was associated with greater BMD increase at the hip over the 36-month posttransplant period. Cinacalcet was well tolerated. Our results suggest that cinacalcet may have a small but favorable effect on bone density following kidney transplantation.

  20. Lipophilic index, kidney function, and kidney function decline.

    PubMed

    Xu, H; Ärnlöv, J; Sandhagen, B; Risérus, U; Lindholm, B; Lind, L; Carrero, J J

    2016-12-01

    Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended re-examination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction ≥30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m(2) 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m(2), p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). A high LI was associated with lower kidney function, kidney function decline, and CKD progression. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by

  1. Musculoskeletal Health, Kidney and Liver Function in Retired Jockeys.

    PubMed

    Cullen, S; Donohoe, A; McGoldrick, A; McCaffrey, N; Davenport, C; Byrne, B; Donaghy, C; Tormey, W; Smith, D; Warrington, G

    2015-11-01

    The long-term implications of making-weight daily on musculoskeletal health and functioning of the kidney and liver remain unknown. This study aimed to investigate musculoskeletal health and kidney and liver function in a group of retired jockeys. 28 retired male jockeys (age 50-70 years) provided fasting blood samples for markers of bone metabolism and kidney and liver function. A dual-energy x-ray absorptiometry (DXA) scan was performed for the assessment of bone mineral density (BMD). Established reference ranges were used for interpretation of results. Comparisons were made between retired jockeys based on the professional racing licence held: Flat, National Hunt or Dual. Mean whole-body osteopenia was reported, with no differences between groups. Bone markers, micronutrients, electrolytes and associated hormones, and markers for kidney and liver function were within clinical normative ranges. No differences existed between groups. Results indicate the retired jockeys in this study do not demonstrate compromised bone health or kidney and liver function. However, the retired jockeys may not have undergone chronic weight cycling in the extreme manner evident in present-day jockeys, indicating the next generation of jockeys may face more of a problem. Jockeys should be tracked longitudinally throughout their racing career and beyond.

  2. Lumbar Herniation of Kidney following Iliac Crest Bone Harvest

    PubMed Central

    2016-01-01

    The iliac crest is a popular source for autogenous bone harvesting, but the process is rife with complications. This case report presents a patient that experienced incisional lumbar herniation of her kidney following an iliac crest bone harvesting procedure. A discussion is included on the underappreciated complications of this procedure and recommendations for improving outcomes with more thorough evaluation and documentation. PMID:28042490

  3. 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

  4. [Mineral-bone disorder with chronic kidney disease].

    PubMed

    Sobotová, D; Zharfbin, A; Neobálková, M; Svojanovský, J; Soucek, M

    2007-01-01

    Mineral-bone disorder in chronic kidney disease is a clinical syndrome provoked by the combination of three factors: abnormal laboratory results, bone morphology disorder and extra-bone calcification. Its onset in adult age is linked with a decrease in glomerular filtration (GF < 1 ml/s). Fully developed forms occur in the course of regular dialysis treatment. The use of the traditional denomination "renal osteodystrophy" is currently restricted to the bone morphology finding. As there are two threshold types of bone turnover (low and high) and two degrees of mineralisation (low and normal), there is a total of four basic variants of mineral-bone disorder. The high turnover variants--secondary hyperparathyreosis and a combined disorder--are still the most frequent and are diagnosed in 70 to 80% of cases. Low turnover disorders include osteomalatia (OM) and adynamic bone disease (ABD). While OM is becoming increasingly rare, the occurrence of ABD is on the rise. The main reason for this may be the steady growth in the age of dialised patients and a number of risk factors, as well as treatment with inadequately high doses of vitamin D. Progressive chronic kidney disease may be linked with D-hormone deficit, negative calcium balance and with positive phosphate balance. Phosphates become a key factor in the development and progression of secondary hyperparathyreosis and extra-bone calcification in the case of D-hormone substitution. Therefore, maintaining a good phosphate balance by restricting their intake or by reducing their intestinal resorption through the use of phosphate binders is the most efficient therapeutic procedure. In patients with chronic kidney failure, adequate dialysis treatment is necessary. Hyperphosphatemia and extra-bone calcification are new independent risk factors of cardiovascular morbidity and mortality.

  5. Role of Bone Biopsy in Stages 3 to 4 Chronic Kidney Disease

    PubMed Central

    Gal-Moscovici, Anca; Sprague, Stuart M.

    2008-01-01

    Secondary hyperparathyroidism develops relatively early in chronic kidney disease as a consequence of impaired phosphate, calcium, and vitamin D homeostasis. The disease state in chronic kidney disease, which includes the histologic features of bone disease, defined as renal osteodystrophy, and the hormonal and biochemical disturbances, have recently been redefined as a disease syndrome and is referred to as “chronic kidney disease–mineral and bone disorder.” As chronic kidney disease progresses, specific histologic disturbances in the bone develop, which may or may not be predictable from the biochemical and hormonal changes that are associated with chronic kidney disease. In addition, patients may have had underlying bone disease before developing kidney failure or may have been treated with agents that will alter the classical pathologic findings of the bones in chronic kidney disease and their relation to parathyroid hormone. Thus, in stage 5 chronic kidney disease, bone biopsy with quantitative histomorphometric analysis is considered the gold standard in the diagnosis of renal osteodystrophy. In contrast to stage 5 chronic kidney disease, there are very few data on the histologic changes in bone in earlier stages of chronic kidney disease. There also is no adequate information on the etiopathogenesis of bone disease in stages 3 and 4 chronic kidney disease. Thus, because biochemical data cannot predict bone pathology in stages 3 and 4 chronic kidney disease, bone biopsy should be used to define these bone changes and to allow appropriate therapeutic approaches. PMID:18988703

  6. Five-year clinical effects of donor bone marrow cells infusions in kidney allograft recipients: improved graft function and higher graft survival.

    PubMed

    Solgi, Ghasem; Gadi, Vijayakrishna; Paul, Biswajit; Mytilineos, Joannis; Pourmand, Gholamreza; Mehrsai, Abdolrasoul; Ranjbar, Moslem; Mohammadnia, Mousa; Nikbin, Behrouz; Amirzargar, Ali Akbar

    2013-01-01

    Augmentation of microchimerism in solid organ transplant recipients by donor bone marrow cells (DBMC) infusion may promote immune hyporesponsiveness and consequently improve long-term allograft survival. Between March 2005 and July 2007, outcomes for 20 living unrelated donor (LURD) primary kidney recipients with concurrent DBMC infusion (an average of 2.19 ± 1.13 x 10⁹ donor cells consisting of 2.66 ± 1.70 x 10⁷ CD34⁺ cells) were prospectively compared with 20 non-infused control allograft recipients given similar conventional immunosuppressive regimens. With five years of clinical follow up, a total of 11 cases experienced rejection episodes (3 DBMI patients vs. 8 controls, p = 0.15). One DBMC-infused patient experienced chronic rejection vs. two episodes (1 biopsy-confirmed) in the control patients. Actuarial and death-censored 5-y graft survival was significantly higher in infused patients compared with controls (p = 0.01 and p = 0.03, respectively). Long-term graft survival was significantly associated with pre-transplant anti-HLA antibodies (p = 0.01), slightly with peripheral microchimerism (p = 0.09) and CD4⁺CD25⁺FoxP3⁺ T cells (p = 0.09). Immunosuppressant dosing was lower in infused patients than controls, particularly for mycophenolate mofetil (p = 0.001). The current findings as well as our previous reports on these patients indicates clinical improvement in long-term graft survival of renal transplant patients resulting from low-dose DBMC infusion given without induction therapy.

  7. SIRT1 and Kidney Function

    PubMed Central

    Guan, Yi; Hao, Chuan-Ming

    2016-01-01

    Background SIRT1 is a nicotinamide adenine dinucleotide-dependent deacetylase belonging to the class III histone deacetylases. Abundantly expressed in the kidney, especially in the renal medulla, SIRT1 is closely involved in renal physiology and pathology. Summary SIRT1 targets both histone and nonhistone proteins, participates in many important signaling pathways and mediates the regulation of longevity, metabolic homeostasis, acute stress response and DNA integrity. With regard to the kidney, SIRT1 attenuates diabetic albuminuria, reduces blood pressure and related cardiovascular diseases, resists acute kidney injury, delays kidney fibrogenesis, promotes cyst formation and benefits renal ageing. Key Messages This review summarizes the biology of SIRT1 and focuses on the latest studies concerning SIRT1 as a potential therapeutic target for kidney diseases. PMID:27536685

  8. 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

  9. Altered material properties are responsible for bone fragility in rats with chronic kidney injury.

    PubMed

    Iwasaki, Yoshiko; Kazama, Junichiro J; Yamato, Hideyuki; Matsugaki, Aira; Nakano, Takayoshi; Fukagawa, Masafumi

    2015-12-01

    Chronic kidney disease (CKD) is associated with an increased risk of fragility fractures, but the underlying pathophysiological mechanism remains obscure. We performed an in vivo experimental study to examine the roles of uremia and abnormal mineral/parathyroid metabolism in the development of bone metabolic abnormalities in uremic rats. Male Sprague-Dawley rats were divided into four groups, comprising sham operation (high turnover bone control=HTB-Cont), 5/6-nephrectomy (high turnover bone nephrectomized=HTB-Nx), thyroparathyroidectomy (low turnover bone control=LTB-Cont), and thyroparathyroidectomy plus 5/6 nephrectomy (low turnover bone nephrectomized=LTB-Nx), and maintained for 16 weeks. Uremia was successfully created in the LTB-Nx and HTB-Nx groups, while hyperparathyroidism was only found in the HTB-Nx group. Cancellous bone histomorphometry revealed significantly higher bone turnover in the HTB-Nx group than in the LTB-Nx group. Storage modulus at 1 Hz and tan delta in cortical bone of the femur, which represent the viscoelastic mechanical properties, were significantly lower in both Nx groups than in the Cont groups regardless of bone metabolism. Pentosidine-to-matrix ratio was increased and crystallinity was decreased in both Nx groups regardless of bone turnover. Mineral-to-matrix ratio was significantly decreased in the HTB-Nx group, but increased in the LTB-Nx group. Enzymatic collagen crosslinks were decreased in the HTB-Nx group. The degree of orientation of the c-axis in carbonated hydroxyapatite (biological apatite=BAp) crystallites was decreased in both Nx groups regardless of bone metabolism. Stepwise multivariate regression revealed that pentosodine-to-matrix ratio and BAp preferential c-axis orientation were significantly associated with storage modulus and tan delta. In conclusion, bone elastic mechanical properties deteriorated regardless of bone metabolism or bone mass in rats with chronic kidney injury. Various changes in bone mineral

  10. From bone abnormalities to mineral metabolism dysregulation in autosomal dominant polycystic kidney disease.

    PubMed

    Mekahli, Djalila; Bacchetta, Justine

    2013-11-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of kidney failure. It is a systemic disorder, not only affecting the kidneys, but also associated with cyst formation in other organs such as the liver, spleen, pancreas, and seminal vesicles. Other extra-renal symptoms may consist of intracranial arterial aneurysms, cardiac valvular defects, abdominal and inguinal hernias and colonic diverticulosis. Very little is known regarding bone involvement in ADPKD; however, recent evidence has revealed the potential role of fibroblast growth factor 23 (FGF23). FGF23 is an endocrine fibroblast growth factor acting in the kidney as a phosphaturic hormone and a suppressor of active vitamin D with key effects on the bone/kidney/parathyroid axis, and has been shown to increase in patients with ADPKD, even with normal renal function. The aim of this review is to provide an overview of bone and mineral abnormalities found in experimental models and in patients with ADPKD, and to discuss the possible role of FGF23 in this disease.

  11. Allopurinol and kidney function: An update.

    PubMed

    Stamp, Lisa K; Chapman, Peter T; Palmer, Suetonia C

    2016-01-01

    Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing debate about optimal allopurinol dosing in gout patients with chronic kidney disease. Given that gout is common in patients with renal impairment, clinicians need to be aware of the relationships between serum urate and kidney function as well as the effects of allopurinol on kidney function and vice versa. The use of allopurinol in patients on dialysis is an understudied area. Dialysis reduces plasma oxypurinol concentrations, therefore the dose and time of administration in relationship to dialysis need to be carefully considered. Recently, it has been suggested that there may be a role for allopurinol in patients with chronic kidney disease without gout. Observational studies have reported an association between serum urate and chronic kidney disease and end stage renal failure. The effect of urate lowering therapy with allopurinol on progression of kidney disease has been examined in small studies with varying results. Larger clinical trials are currently underway. This review will examine the relationships between allopurinol and kidney function in adults with and without renal disease and address allopurinol dosing in gout patients with impaired kidney function.

  12. Update on Mineral and Bone Disorders in Chronic Kidney Disease.

    PubMed

    Foster, Jonathan D

    2016-11-01

    The inappropriate phosphorus retention observed in chronic kidney disease is central to the pathophysiology of mineral and bone disorders observed in these patients. Subsequent derangements in serum fibroblast growth factor 23, parathyroid hormone, and calcitriol concentrations play contributory roles. Therapeutic intervention involves dietary phosphorus restriction and intestinal phosphate binders in order to correct phosphorus retention and maintain normocalcemia. Additional therapies may be considered to normalize serum fibroblast growth factor 23 and parathyroid hormone. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Vascular calcification, bone and mineral metabolism after kidney transplantation

    PubMed Central

    D’Marco, Luis; Bellasi, Antonio; Mazzaferro, Sandro; Raggi, Paolo

    2015-01-01

    The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article. PMID:26722649

  14. Kidney Function After the First Kidney Stone Event.

    PubMed

    Haley, William E; Enders, Felicity T; Vaughan, Lisa E; Mehta, Ramila A; Thoman, Maxton E; Vrtiska, Terri J; Krambeck, Amy E; Lieske, John C; Rule, Andrew D

    2016-12-01

    To determine whether there is a persistent decline in kidney function after the first kidney stone event. Incident symptomatic stone formers and age- and sex-matched controls underwent 2 study visits 90 days apart to assess kidney function, complete a survey, and have their medical records reviewed. Kidney function was compared between stone formers and controls adjusting for clinical, blood, and urine risk factors. There were 384 stone formers and 457 controls. At visit 1, a median of 104 days after the stone event, stone formers compared with controls had similar serum creatinine (0.86 vs 0.84 mg/dL; P=.23), higher serum cystatin C (0.83 vs 0.72 mg/L; P<.001), higher urine protein (34.2 vs 19.7 mg/24 h; P<.001) levels, and were more likely to have albuminuria (24 h urine albumin >30 mg: 5.4% vs 2.2%; P=.02). Findings were similar after adjustment for risk factors and at visit 2, a median of 92 days after visit 1. In the 173 stone formers with serum creatinine levels from care before study participation, the mean serum creatinine level was 0.84 mg/dL before the stone event, increased to 0.97 mg/dL (P<.001) at the stone event, but returned to 0.85 mg/dL (P=.38) after the stone event (visit 1). Incident symptomatic stone formers have a rise in serum creatinine levels that resolves. However, stone formers have sustained higher cystatin C levels and proteinuria that may affect long-term risk of chronic kidney disease. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  15. Function of osteocytes in bone.

    PubMed

    Aarden, E M; Burger, E H; Nijweide, P J

    1994-07-01

    Although the structural design of cellular bone (i.e., bone containing osteocytes that are regularly spaced throughout the bone matrix) dates back to the first occurrence of bone as a tissue in evolution, and although osteocytes represent the most abundant cell type of bone, we know as yet little about the role of the osteocyte in bone metabolism. Osteocytes descend from osteoblasts. They are formed by the incorporation of osteoblasts into the bone matrix. Osteocytes remain in contact with each other and with cells on the bone surface via gap junction-coupled cell processes passing through the matrix via small channels, the canaliculi, that connect the cell body-containing lacunae with each other and with the outside world. During differentiation from osteoblasts to mature osteocyte the cells lose a large part of their cell organelles. Their cell processes are packed with microfilaments. In this review we discuss the various theories on osteocyte function that have taken in consideration these special features of osteocytes. These are 1) osteocytes are actively involved in bone turnover; 2) the osteocyte network is through its large cell-matrix contact surface involved in ion exchange; and 3) osteocytes are the mechanosensory cells of bone and play a pivotal role in functional adaptation of bone. In our opinion, especially the last theory offers an exciting concept for which some biomechanical, biochemical, and cell biological evidence is already available and which fully warrants further investigations.

  16. Bone imaging and fracture risk assessment in kidney disease.

    PubMed

    Jamal, Sophie A; Nickolas, Thomas L

    2015-06-01

    Fractures are more common and are associated with greater morbidity and morality in patients with kidney disease than in members of the general population. Thus, it is troubling that in chronic kidney disease (CKD) patients there has been a paradoxical increase in fracture rates over the past 20 years compared to the general population. Increased fracture incidence in CKD patients may be driven in part by the lack of screening for fracture risk. In the general population, dual energy X-ray absorptiometry (DXA) is the clinical standard to stratify fracture risk, and its use has contributed to decreases in fracture incidence. In contrast, in CKD, fracture risk screening with DXA has been uncommon due to its unclear efficacy in predicting fracture and its inability to predict type of renal osteodystrophy. Recently, several prospective studies conducted in patients across the spectrum of kidney disease have demonstrated that bone mineral density measured by DXA predicts future fracture risk and that clinically relevant information regarding fracture risk is provided by application of the World Health Organization cutoffs for osteopenia and osteoporosis to DXA measures. Furthermore, novel high-resolution imaging tools, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have been used to elucidate the effects of kidney disease on cortical and trabecular microarchitecture and bone strength and to identify potential targets for strategies that protect against fractures. This review will discuss the updated epidemiology of fractures in CKD, fracture risk screening by DXA, and the utility of state-of-the art imaging methods to uncover the effects of kidney disease on the skeleton.

  17. Biomarkers in chronic kidney disease, from kidney function to kidney damage

    PubMed Central

    Lopez-Giacoman, Salvador; Madero, Magdalena

    2015-01-01

    Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m2. Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD. PMID:25664247

  18. 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

    2017-08-10

    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

  19. Chronic Kidney Disease: Mineral and Bone Disorder in Children

    PubMed Central

    Wesseling-Perry, Katherine; Salusky, Isidro B.

    2014-01-01

    Childhood and adolescence are crucial times for the development of a healthy skeletal and cardiovascular system. Disordered mineral and bone metabolism accompany chronic kidney disease (CKD) and present significant obstacles to optimal bone strength, final adult height, and cardiovascular health. Early increases in bone and plasma fibroblast growth factor 23 (FGF23) are associated with early defects in skeletal mineralization. Later in the course of CKD, secondary hyperparathyroidism—due to a combination of declining calcitriol values and phosphate retention—results in high turnover renal osteodystrophy while elevated levels of both phosphate and FGF23 contribute to cardiovascular disease. Treatment of hyperphosphatemia and secondary hyperparathyroidism improves high turnover bone disease but fails to correct defects in skeletal mineralization. Since overtreatment may result in adynamic bone disease, growth failure, hypercalcemia, and progression of cardiovascular calcifications, therapy must therefore be carefully titrated to maintain optimal serum biochemical parameters according to stage of CKD. Newer therapeutic agents and new treatment paradigms may effectively suppress serum PTH levels while limiting intestinal calcium absorption and skeletal FGF23 stimulation and may provide future therapeutic alternatives for children with CKD. PMID:23465503

  20. Myoglobinuria with acute renal failure and hot kidneys seen on bone imaging

    SciTech Connect

    Sheth, K.J.; Sty, J.R.; Johnson, F.; Tisdale, P.

    1984-09-01

    We report a case of myoglobinuria secondary to prolonged seizures. The child showed ''hot kidneys'' with bone scintigraphy. The disease entity and etiologies of nontraumatic rhabdomyolysis are discussed.

  1. The fate of bone marrow-derived cells carrying a polycystic kidney disease mutation in the genetically normal kidney

    PubMed Central

    2012-01-01

    Background Polycystic Kidney Disease (PKD) is a genetic condition in which dedifferentiated and highly proliferative epithelial cells form renal cysts and is frequently treated by renal transplantation. Studies have reported that bone marrow-derived cells give rise to renal epithelial cells, particularly following renal injury as often occurs during transplantation. This raises the possibility that bone marrow-derived cells from a PKD-afflicted recipient could populate a transplanted kidney and express a disease phenotype. However, for reasons that are not clear the reoccurrence of PKD has not been reported in a genetically normal renal graft. We used a mouse model to examine whether PKD mutant bone marrow-derived cells are capable of expressing a disease phenotype in the kidney. Methods Wild type female mice were transplanted with bone marrow from male mice homozygous for a PKD-causing mutation and subjected to renal injury. Y chromosome positive, bone marrow-derived cells in the kidney were assessed for epithelial markers. Results Mutant bone marrow-derived cells were present in the kidney. Some mutant cells were within the bounds of the tubule or duct, but none demonstrated convincing evidence of an epithelial phenotype. Conclusions Bone marrow-derived cells appear incapable of giving rise to genuine epithelial cells and this is the most likely reason cysts do not reoccur in kidneys transplanted into PKD patients. PMID:22931547

  2. Roles of the kidney in the formation, remodeling and repair of bone.

    PubMed

    Wei, Kai; Yin, Zhiwei; Xie, Yuansheng

    2016-06-01

    The relationship between the kidney and bone is highly complex, and the kidney plays an important role in the regulation of bone development and metabolism. The kidney is the major organ involved in the regulation of calcium and phosphate homeostasis, which is essential for bone mineralization and development. Many substances synthesized by the kidney, such as 1,25(OH)2D3, Klotho, bone morphogenetic protein-7, and erythropoietin, are involved in different stages of bone formation, remodeling and repair. In addition, some cytokines which can be affected by the kidney, such as osteoprotegerin, sclerostin, fibroblast growth factor -23 and parathyroid hormone, also play important roles in bone metabolism. In this paper, we summarize the possible effects of these kidney-related cytokines on bone and their possible mechanisms. Most of these cytokines can interact with one another, constituting an intricate network between the kidney and bone. Therefore, kidney diseases should be considered among patients presenting with osteodystrophy and disturbances in bone and mineral metabolism, and treatment for renal dysfunction may accelerate their recovery.

  3. Pathophysiology of the chronic kidney disease-mineral bone disorder.

    PubMed

    Hruska, Keith A; Seifert, Michael; Sugatani, Toshifumi

    2015-07-01

    The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. The causes of the CKD-MBD are not well known and they will be discussed in this review The discovery of WNT (portmanteau of wingless and int) inhibitors, especially Dickkopf 1, produced during renal repair and participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical, leading to the finding that activin A is a second renal repair factor circulating in increased levels during CKD. Activin A derives from peritubular myofibroblasts of diseased kidneys, where it stimulates fibrosis, and decreases tubular klotho expression. The type 2 activin A receptor, ActRIIA, is decreased by CKD in atherosclerotic aortas, specifically in vascular smooth muscle cells (VSMC). Inhibition of activin signaling by a ligand trap inhibited CKD induced VSMC dedifferentiation, osteogenic transition and atherosclerotic calcification. Inhibition of activin signaling in the kidney decreased renal fibrosis and proteinuria. These studies demonstrate that circulating renal repair factors are causal for the CKD-MBD and CKD associated cardiovascular disease, and identify ActRIIA signaling as a therapeutic target in CKD that links progression of renal disease and vascular disease.

  4. Emerging functions of autophagy in kidney transplantation.

    PubMed

    Pallet, N; Livingston, M; Dong, Z

    2014-01-01

    In response to ischemic, toxic or immunological insults, the more frequent injuries encountered by the kidney, cells must adapt to maintain vital metabolic functions and avoid cell death. Among the adaptive responses activated, autophagy emerges as an important integrator of various extracellular and intracellular triggers (often related to nutrients availability or immunological stimuli), which, as a consequence,may regulate cell viability, and also immune functions,both innate or adaptive. The aim of this review is to make the synthesis of the recent literature on the implications of autophagy in the kidney transplantation field and to discuss the future directions for research.

  5. Bone and mineral metabolism and fibroblast growth factor 23 levels after kidney donation.

    PubMed

    Young, Ann; Hodsman, Anthony B; Boudville, Neil; Geddes, Colin; Gill, John; Goltzman, David; Jassal, Sarbjit Vanita; Klarenbach, Scott; Knoll, Gregory; Muirhead, Norman; Prasad, G V Ramesh; Treleaven, Darin; Garg, Amit X

    2012-06-01

    Living kidney donation offers a unique setting to study changes in phosphate and vitamin D homeostasis attributable to mild isolated decreases in estimated glomerular filtration rate (eGFR). Cross-sectional study. 198 living kidney donors and 98 nondonor controls from 9 transplant centers across 3 countries. For donors, median time after donation was 5.3 years. At assessment, donors had a lower eGFR than controls (73 vs 98 mL/min/1.73 m(2)). Living kidney donation (mildly decreased eGFR). Biochemical markers of chronic kidney disease-mineral and bone disorder. Serum creatinine, total serum calcium, serum and urine inorganic phosphate, plasma intact parathyroid hormone, serum calcidiol and calcitriol, renal fractional excretion of inorganic phosphate, and intact serum fibroblast growth factor 23 (FGF-23). Serum FGF-23 levels were significantly higher in donors (38.1 vs 29.7 pg/mL; P < 0.001). For every 10-mL/min/1.73 m(2) decrease in eGFR, FGF-23 level was higher by 3.2 (95% CI, 2.0-4.4) pg/mL. Compared with controls, donors showed higher renal tubular fractional excretion of inorganic phosphate (17.8% vs 12.3%; P < 0.001), lower serum phosphate (0.97 vs 1.02 mmol/L; P = 0.03), and lower serum calcitriol values (63 vs 77 pmol/L; P < 0.001). Serum calcium levels were not significantly different between the 2 groups. Plasma intact parathyroid hormone levels were significantly higher in donors (5.7 vs 5.0 pmol/L; P = 0.03), but were not correlated with FGF-23 or calcitriol levels. Enrollment of a small proportion of past donors at participating centers; assessment of only postdonation values; unable to assess seasonal variation or other temporal patterns in biochemical markers; assessment of kidney function was based on eGFR, not measured GFR. The FGF-23 pathway may be activated in living kidney donors who show early biochemical changes compatible with chronic kidney disease-mineral and bone disorder. Whether these changes influence bone mineral density and fracture

  6. Differential response of bone and kidney to ACEI in db/db mice: A potential effect of captopril on accelerating bone loss.

    PubMed

    Zhang, Yan; Li, Xiao-Li; Sha, Nan-Nan; Shu, Bing; Zhao, Yong-Jian; Wang, Xin-Luan; Xiao, Hui-Hui; Shi, Qi; Wong, Man-Sau; Wang, Yong-Jun

    2017-04-01

    The components of renin-angiotensin system (RAS) are expressed in the kidney and bone. Kidney disease and bone injury are common complications associated with diabetes. This study aimed to investigate the effects of an angiotensin-converting enzyme inhibitor, captopril, on the kidney and bone of db/db mice. The db/db mice were orally administered by gavage with captopril for 8weeks with db/+ mice as the non-diabetic control. Serum and urine biochemistries were determined by standard colorimetric methods or ELISA. Histological measurements were performed on the kidney by periodic acid-schiff staining and on the tibial proximal metaphysis by safranin O and masson-trichrome staining. Trabecular bone mass and bone quality were analyzed by microcomputed tomography. Quantitative polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. Captopril significantly improved albuminuria and glomerulosclerosis in db/db mice, and these effects might be attributed to the down-regulation of angiotensin II expression and the expression of its down-stream profibrotic factors in the kidney, like connective tissue growth factor and vascular endothelial growth factor. Urinary excretion of calcium and phosphorus markedly increased in db/db mice in response to captopril. Treatment with captopril induced a decrease in bone mineral density and deterioration of trabecular bone at proximal metaphysis of tibia in db/db mice, as shown in the histological and reconstructed 3-dimensional images. Even though captopril effectively reversed the diabetes-induced changes in calcium-binding protein 28-k and vitamin D receptor expression in the kidney as well as the expression of RAS components and bradykinin receptor-2 in bone tissue, treatment with captopril increased the osteoclast-covered bone surface, reduced the osteoblast-covered bone surface, down-regulated the expression of type 1 collagen and transcription factor runt-related transcription

  7. [Kidney function and renal cancer surgery].

    PubMed

    Izzedine, Hassan; Méjean, Arnaud; Escudier, Bernard

    2014-02-01

    Although radical nephrectomy is still practiced in many patients with large renal tumors, oncology and nephrology arguments for kidney-sparing approach for small renal masses has taken over this first. Indeed, partial nephrectomy provides equivalent oncologic results while preserving renal function and thereby limit morbidity and cardiovascular mortality related to chronic kidney disease. In addition, patients who develop kidney cancer often have medical comorbidities that may affect renal function, such as diabetes and hypertension. Histological examination of renal tissue adjacent to the tumor showed significant pathological changes in the majority of patients. For elderly patients or patients with comorbidities, active surveillance allows kidney-sparing approach with extremely low rates of progression and metastasis of cancer disease. Despite these significant advances in understanding for the treatment of small renal masses, partial nephrectomy remains underused. Better management must take into account the preservation of renal function in order to increase overall survival. A strategy for the systematic evaluation of renal function in patients with CR, with multidisciplinary staff (nephrologist urologist and oncologist), is therefore highly desirable.

  8. Leptin in chronic kidney disease: a link between hematopoiesis, bone metabolism, and nutrition.

    PubMed

    Zhang, Jingjing; Wang, Ningning

    2014-06-01

    Anemia, dyslipidemia, malnutrition, together with mineral and bone disorders are common complications in patients with chronic kidney disease (CKD). All are associated with increased risk of mortality. Leptin is a small peptide hormone that is mainly but not exclusively produced in adipose tissue. It is also secreted by normal human osteoblasts, subchondral osteoblasts, placental syncytiotrophoblasts, and the gastric epithelium. Leptin binds to its receptors in the hypothalamus to regulate bone metabolism and food intake. Leptin also has several other important metabolic effects on peripheral tissues, including the liver, skeletal muscle, and bone marrow. Leptin is cleared principally by the kidney. Not surprisingly, serum leptin appears to increase concurrently with declines in the glomerular filtration rate in patients with CKD. A growing body of evidence suggests that leptin might be closely related to hematopoiesis, nutrition, and bone metabolism in CKD patients. Results are conflicting regarding leptin in patients with CKD, in whom both beneficial and detrimental effects on uremia outcome are found. This review elucidates the discovery of leptin and its receptors, changes in serum or plasma leptin levels, the functions of leptin, relationships between leptin and the complications mentioned above, and pharmaceutical interventions in serum leptin levels in patients with CKD.

  9. Measurement of renal function in patients with chronic kidney disease.

    PubMed

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J

    2013-10-01

    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease.

  10. Measurement of renal function in patients with chronic kidney disease

    PubMed Central

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J

    2013-01-01

    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease. PMID:23802624

  11. Hereditary hypophosphatemias: new genes in the bone-kidney axis.

    PubMed

    Negri, Armando L

    2007-08-01

    Hypophosphatemia due to isolated renal phosphate wasting is a genetically heterogeneous disease. Two new genes linked to two different forms of hereditary hypophosphatemias have recently been described. Autosomal recessive form of hypophosphatemic rickets was mapped to chromosome 4q21 and identified homozygous mutations in dentin matrix protein 1 (DMP1) gene, which encodes a non-collagenous bone matrix protein. Intact plasma levels of the phosphaturic protein FGF23 (fibroblast growth factor 23) were clearly elevated in some of the affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels, and suggesting that DMP1 may regulate FGF23 expression. Hereditary hypophosphatemic rickets with hypercalciuria is another rare disorder of autosomal recessive inheritance. Affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption. The disease was mapped to a 1.6 Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaPi-IIc. This was the first demonstration that NaPi-IIc has a key role in the regulation of phosphate homeostasis. Thus, DMP1 and NaPi-IIc add two new members to the bone-kidney axis proposed since it was discovered that the first phosphatonin, FGF23, was of osteoblastic/osteocyte origin. This provides a mechanism for the skeleton to communicate with the kidney to coordinate the mineralization of extracelular matrix and the renal handling of phosphate.

  12. Chromatin dynamics in kidney development and function.

    PubMed

    Bechtel-Walz, Wibke; Huber, Tobias B

    2014-06-01

    Epigenetic mechanisms are fundamental key features of developing cells connecting developmental regulatory factors to chromatin modification. Changes in the environment during renal development can have long-lasting effects on the permanent tissue structure and the level of expression of important functional genes. These changes are believed to contribute to kidney disease occurrence and progression. Although the mechanisms of early patterning and cell fate have been well described for renal development, little is known about associated epigenetic modifications and their impact on how genes interact to specify the renal epithelial cells of nephrons and how this specification is relevant to maintaining normal renal function. A better understanding of the renal cell-specific epigenetic modifications and the interaction of different cell types to form this highly complex organ will not only help to better understand developmental defects and early loss of kidney function in children, but also help to understand and improve chronic disease progression, cell regeneration and renal aging.

  13. Sexual function in chronic kidney disease.

    PubMed

    Anantharaman, Priya; Schmidt, Rebecca J

    2007-04-01

    Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.

  14. Aquaporins in avian kidneys: function and perspectives.

    PubMed

    Nishimura, Hiroko; Yang, Yimu

    2013-12-01

    For terrestrial vertebrates, water economy is a prerequisite for survival, and the kidney is their major osmoregulatory organ. Birds are the only vertebrates other than mammals that can concentrate urine in adaptation to terrestrial environments. Aquaporin (AQP) and glyceroporin (GLP) are phylogenetically old molecules and have been found in plants, microbial organisms, invertebrates, and vertebrates. Currently, 13 AQPs/aquaGLPs and isoforms are known to be present in mammals. AQPs 1, 2, 3, 4, 6, 7, 8, and 11 are expressed in the kidney; of these, AQPs 1, 2, 3, 4, and 7 are shown to be involved in fluid homeostasis. In avian kidneys, AQPs 1, 2, 3, and 4 have been identified and characterized. Also, gene and/or amino acid sequences of AQP5, AQP7, AQP8, AQP9, AQP11, and AQP12 have been reported in birds. AQPs 2 and 3 are expressed along cortical and medullary collecting ducts (CDs) and are responsible, respectively, for the water inflow and outflow of CD epithelial cells. While AQP4 plays an important role in water exit in the CD of mammalian kidneys, it is unlikely to participate in water outflow in avian CDs. This review summarizes current knowledge on structure and function of avian AQPs and compares them to those in mammalian and nonmammalian vertebrates. Also, we aim to provide input into, and perspectives on, the role of renal AQPs in body water homeostasis during ontogenic and phylogenetic advancement.

  15. Functional changes in the aging kidney.

    PubMed

    Esposito, Ciro; Dal Canton, Antonio

    2010-01-01

    The aging process results in remarkable changes in the kidney. These changes are both anatomical and functional and have been considered the cause of the increased propensity of the elderly to acute or chronic renal failure. However, the majority of the early studies on aging enrolled institutionalized elderly patients with several comorbidities such as hypertension and heart disease which could by themselves induce renal alterations. Recently the selection of subjects lacking renal disease or processes known to affect renal function has demonstrated that aging changes are less pronounced in healthy aged subjects. Nonetheless, understanding aging-induced renal changes may help to prevent life-threatening kidney disease. This review will focus on glomerular hemodynamics, and on renal sodium and potassium handling and diluting and concentrating ability.

  16. [New Developments in CKD-MBD. Bone quality and fracture in patients with chronic kidney disease].

    PubMed

    Iwasaki, Yoshiko; Yamato, Hideyuki

    2014-12-01

    Chronic kidney disease (CKD) patients have an extremely increased risk of fragility fractures, but the underling pathophysiological mechanisms remain obscure. Recently, the progresses of analysis technology have revealed the changes of bone quality in CKD condition. In particular, we can observe the characteristic changes of bone microarchitecture and bone chemical compositions in both human bone biopsy samples and experimental animal bones. Here, I will provide a short review on these bone quality factors and discuss on the relationship between bone quality and fracture in CKD patients.

  17. Bone mineral density predicts fractures in chronic kidney disease.

    PubMed

    West, Sarah L; Lok, Charmaine E; Langsetmo, Lisa; Cheung, Angela M; Szabo, Eva; Pearce, Dawn; Fusaro, Maria; Wald, Ron; Weinstein, Jordan; Jamal, Sophie A

    2015-05-01

    Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and/or high-resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm3 (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD.

  18. Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications.

    PubMed

    Salanova Villanueva, Laura; Sánchez González, Carmen; Sánchez Tomero, José Antonio; Aguilera, Abelardo; Ortega Junco, Esther

    2016-01-01

    Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

  19. Serendipitous finding of transitional cell carcinoma of the kidney on bone and gallium imaging

    SciTech Connect

    Moreno, A.J.; Toney, M.A.; Griffith, J.C.; Rodriguez, A.A.; Turnbull, G.L. )

    1991-03-01

    A 50-year-old woman presented with low back pain. Bone scintigraphy showed a focus of increased activity in the upper pole of the left kidney. Subsequent Ga-67 citrate scintigraphy demonstrated this same abnormal focus as a region of increased activity. Ultrasonography showed a renal mass in the upper pole of the left kidney. At surgery a transitional cell carcinoma of the upper pole of the left kidney was found.

  20. [Renal transplantation without maintenance immunosuppression. Identical twins and kidney transplantation following a successful bone marrow graft].

    PubMed

    Hadi, Riad Abdel; Thomé, Gustavo Gomes; Ribeiro, Adriana Reginato; Manfro, Roberto Ceratti

    2015-01-01

    Renal transplantation without maintenance immunosuppression has been sporadically reported in the literature. The cases include non-adherent patients who discontinued their immunosuppressive medications, transplantation between identical twins, kidney transplantation after a successful bone marrow graft from the same donor and simultaneous bone marrow and kidney transplantation for the treatment of multiple myeloma with associated renal failure. There are also ongoing clinical trials designed to induce donor specific transplant tolerance with infusion of hematopoietic cells from the same kidney donor. Here we describe two cases of renal transplantation without immunosuppression as examples of situations described above.

  1. Delayed Graft Function 5 Months After Living Donor Kidney Transplantation

    PubMed Central

    Schulz, Tim; Pries, Alexandra; Kapischke, Matthias

    2016-01-01

    Patient: Female, 59 Final Diagnosis: Delayed kidney graft function Symptoms: — Medication: — Clinical Procedure: Living donor kidney transplantation Specialty: Transplantology Objective: Unusual clinical course Background: Delayed graft function is a clinical term to describe the failure of the transplanted kidney to function immediately after transplantation. Case Report: A 59-year-old woman suffered from a rare case of delayed graft function lasting 148 days after unrelated living donor kidney transplantation. Until now, 15 years after transplantation, organ function is still good, with serum creatinine levels about 1.4 to 2.0 mg/dl. Conclusions: Even after prolonged graft dysfunction, good graft function can be achieved. PMID:26915643

  2. [Chronic kidney disease (CKD) and bone. From renal osteodystrophy to CKD-MBD: new disease entity].

    PubMed

    Tsukamoto, Yusuke

    2009-04-01

    New disease entity "CKD-MBD" was created by the KDIGO (Kidney Disease: Improving Global Outcome) at the controversy conference in 2005. This entity accurately reflects a diversity in mineral and bone disorder associated with CKD. According to this new definition, renal osteodystrophy should be used to express only bone lesion associated with CKD.

  3. 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.

  4. The relationship between calcium kidney stones, arterial stiffness and bone density: unraveling the stone-bone-vessel liaison.

    PubMed

    Fabris, Antonia; Ferraro, Pietro Manuel; Comellato, Gabriele; Caletti, Chiara; Fantin, Francesco; Zaza, Gianluigi; Zamboni, Mauro; Lupo, Antonio; Gambaro, Giovanni

    2015-10-01

    Kidney stone disease is associated with a higher incidence of cardio-vascular (CV) events for still unclear reasons. Reduced bone density is also a frequent finding in calcium kidney stones. The association of reduced bone density with increased vascular stiffness and calcification has been discovered in a number of conditions. We investigated the hypothesis that patients with calcium kidney stones have increased arterial stiffness, which would be associated with reduced bone density and higher CV risk. We compared measures of arterial stiffness [carotid-radial pulse-wave velocity (CR-PWV), carotid-femoral pulse-wave velocity (CF-PWV) and augmentation index (AI)] and of bone density (T-scores determined at lumbar spine, neck and hip) among 42 idiopathic calcium stone formers compared with 42 age- and sex-matched healthy volunteers. Stone formers had higher values of CR-PWV, CF-PWV and AI, and lower values of all T-scores. Furthermore, the prevalence of abnormal arterial stiffness and reduced bone density was significantly higher among stone formers. Statistical adjustment for age, sex, body mass index and other covariates did not change the results. Our study confirms that stone formers have increased arterial stiffness and reduced bone density. Abnormal arterial stiffness appears to be independent of reduced bone density and may explain the higher CV risk observed in stone formers.

  5. Volumetric bone mineral density and bone structure in childhood chronic kidney disease.

    PubMed

    Wetzsteon, Rachel J; Kalkwarf, Heidi J; Shults, Justine; Zemel, Babette S; Foster, Bethany J; Griffin, Lindsay; Strife, C Frederic; Foerster, Debbie L; Jean-Pierre, Darlene K; Leonard, Mary B

    2011-09-01

    Chronic kidney disease (CKD) is associated with increased fracture risk and skeletal deformities. The impact of CKD on volumetric bone mineral density (vBMD) and cortical dimensions during growth is unknown. Tibia quantitative computed tomographic scans were obtained in 156 children with CKD [69 stages 2 to 3, 51 stages 4 to 5, and 36 stage 5D (dialysis)] and 831 healthy participants aged 5 to 21 years. Sex-, race-, and age- or tibia length-specific Z-scores were generated for trabecular BMD (TrabBMD), cortical BMD (CortBMD), cortical area (CortArea) and endosteal circumference (EndoC). Greater CKD severity was associated with a higher TrabBMD Z-score in younger participants (p < .001) compared with healthy children; this association was attenuated in older participants (interaction p < .001). Mean CortArea Z-score was lower (p < .01) in CKD 4-5 [-0.49, 95% confidence interval (CI) -0.80, -0.18)] and CKD 5D (-0.49, 95% CI -0.83, -0.15) compared with healthy children. Among CKD participants, parathyroid hormone (PTH) levels were positively associated with TrabBMD Z-score (p < .01), and this association was significantly attenuated in older participants (interaction p < .05). Higher levels of PTH and biomarkers of bone formation (bone-specific alkaline phosphatase) and resorption (serum C-terminal telopeptide of type 1 collagen) were associated with lower CortBMD and CortArea Z-scores and greater EndoC Z-score (r = 0.18-0.36, all p ≤ .02). CortBMD Z-score was significantly lower in CKD participants with PTH levels above versus below the upper limit of the Kidney Disease Outcome Quality Initiative (KDOQI) CKD stage-specific target range: -0.46 ± 1.29 versus 0.12 ± 1.14 (p < .01). In summary, childhood CKD and secondary hyperparathyroidism were associated with significant reductions in cortical area and CortBMD and greater TrabBMD in younger children. Future studies are needed to establish the fracture implications of these

  6. 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

  7. Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

    PubMed

    Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

    2014-09-05

    Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0

  8. Nephrolithiasis and loss of kidney function

    PubMed Central

    Keddis, Mira T.; Rule, Andrew D.

    2014-01-01

    Purpose of review The prevalence of nephrolithiasis has been on the rise over recent decades. There have also been extensive efforts to identify risk factors for chronic kidney disease (CKD). The purpose of this review is to highlight recent evidence on the association of nephrolithiasis with the development of CKD and end-stage renal disease (ESRD). Recent findings Several epidemiologic studies over the past decade assessed the relationship between history of nephrolithiasis and CKD. Across several studies, patients with nephrolithiasis had about a two-fold higher risk for decreased renal function or need for renal replacement therapy. This risk appears to be independent of risk factors for CKD that are common in stone formers such as hypertension and diabetes mellitus. Specific risk factors for CKD in stone formers include recurrent urinary tract infections, struvite and possibly uric acid stone composition, symptomatic stones, solitary kidney, ileal conduit, neurogenic bladder, and hydronephrosis. Summary Recent evidence has shown a consistent relationship between nephrolithiasis history and an increased risk of CKD and ESRD. Understanding the characteristics that predispose to CKD may better inform how to optimally manage patients with nephrolithiasis and prevent this complication. PMID:23736840

  9. Effects of Reduced Kidney Function Because of Living Kidney Donation on Left Ventricular Mass.

    PubMed

    Altmann, Ursula; Böger, Carsten A; Farkas, Stefan; Mack, Matthias; Luchner, Andreas; Hamer, Okka W; Zeman, Florian; Debl, Kurt; Fellner, Claudia; Jungbauer, Carsten; Banas, Bernhard; Buchner, Stefan

    2017-02-01

    Living kidney donation is associated with a small but significant increase in cardiovascular mortality. In addition, mildly decreased kidney function is associated with an increase of left ventricular mass and with cardiovascular disease in patients with chronic kidney disease. To investigate this association, we evaluated the impact of mildly decreased kidney function after living kidney donation on subclinical cardiac structural and functional changes. In this prospective cohort study, cardiac and renal magnetic resonance imaging and laboratory analyses were performed in 23 living kidney donors (mean age 54±10 years, 52% male) before donation and at 4 and 12 months after nephrectomy. Mean estimated glomerular filtration rate was 102±15 mL min(-1) 1.73 m(-2) before donation and 70±13 mL min(-1) 1.73 m(-2) at 12 months (P<0.001). Left ventricular mass increased from 112±22 to 115±23 g (P<0.001). In addition, heart rate was significantly increased (65±7 to 74±14; P=0.04). Concurrently, kidney and adrenal gland volume increased from 163±33 to 195±34 mL (P<0.001) and from 7.6±2.2 to 8.4±2.4 mL (P=0.032), respectively, as did procollagen type III (Δ0.11 ng/mL, P<0.001) and not N-terminal probrain natriuretic peptide (Δ14 pg/mL, P=0.25). The mild decrease in kidney function after living kidney donation leads to a significant but clinically negligible increase in left ventricular mass 12 months after living kidney donation. This study of a longitudinal analysis of living kidney donors provides direct evidence of a kidney-heart link.

  10. Kidney Function and Prevalent and Incident Frailty

    PubMed Central

    Katz, Ronit; Rifkin, Dena E.; Siscovick, David; Newman, Anne B.; Fried, Linda F.; Sarnak, Mark J.; Odden, Michelle C.; Shlipak, Michael G.

    2013-01-01

    Summary Background and objectives Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants. Design, setting, participants, & measurements CHS enrolled community-dwelling adults age ≥65 years between 1989–1990 and 1992–1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFRcys). Secondary analyses examined eGFR using serum creatinine (eGFRSCr). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity. Results The mean age was 75 years and the median eGFRcys was 73 ml/min per 1.73 m2. Among participants with an eGFRcys <45 ml/min per 1.73 m2, 24% had prevalent frailty. In multivariable analysis and compared with eGFRcys ≥90 ml/min per 1.73 m2, eGFRcys categories of 45–59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15–44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60–75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFRcys categories of 60–75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15–44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45–59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFRSCr were not associated with higher risk of prevalent or incident frailty. Conclusions In

  11. Battleground: chronic kidney disorders mineral and bone disease--calcium obsession, vitamin d, and binder confusion.

    PubMed

    Kovesdy, Csaba P; Mehrotra, Rajnish; Kalantar-Zadeh, Kamyar

    2008-01-01

    Renal osteodystrophy is a significant complication in chronic kidney disease. This condition is referred to as mineral and bone disorders in chronic kidney disease, mainly because of its wider ranging impact, including an association with increased mortality and non-bone-related morbidity. Because most of the abnormalities that characterize mineral and bone disorders in chronic kidney disease (e.g., hyperphosphatemia, secondary hyperparathyroidism) are amenable to therapeutic interventions, this field has also been in the cross-hairs of many pharmaceutical companies. The advent of a number of new therapeutic options for mineral and bone disorders in chronic kidney disease has broadened our armamentarium but has also resulted in an intense marketing battle between pharmaceutical companies. The paucity of randomized, controlled trials in this field has allowed the various companies to promote unilaterally data that fit their needs and to attempt to discredit data that support their competitors' products. Although this attitude is expected and regarded as acceptable in a consumer society, on a scientific level, it has resulted in a polarized and often confused audience: The practicing nephrologists. This article provides a historical overview of how the field of mineral and bone disorders in chronic kidney disease has evolved from a pharmaceutical standpoint, with a critical emphasis of the key moments that resulted in the current acrimonious climate. Also assessed is what the key unanswered questions are in this field, and practical solutions to the discussed issues are provided.

  12. Change in bone mineral density at one year following glucocorticoid withdrawal in kidney transplant recipients.

    PubMed

    Ing, Steven W; Sinnott, Loraine T; Donepudi, Sirisha; Davies, Elizabeth A; Pelletier, Ronald P; Lane, Nancy E

    2011-01-01

    Glucocorticoid (GC) therapy induces deleterious effects on the skeleton in kidney transplantation but studies of GC discontinuation in this population are limited. This study evaluated changes in areal bone mineral density (BMD) with GC withdrawal. Subjects were enrolled one yr after renal transplantation and randomized to continue or stop prednisone; all subjects continued cyclosporine and mycophenolate mofetil. BMD measured by dual-energy X-ray absorptiometry was performed at enrollment and repeated at one yr and values were standardized. Mean ± standard deviation of annualized change in standardized BMD between GC withdrawal vs. continuation group at the lumbar spine was +4.7% ± 5.5 vs. +0.9% ± 5.3 (p = 0.0014); total hip +2.4% ± 4.2 vs. -0.4% ± 4.2 (p = 0.013), and femoral neck +2.1% ± 4.6 vs. +1.0% ± 6.0 (p = 0.37). There was no confounding by prednisone dose prior to enrollment, change in creatinine clearance, weight, or use of bone-active medications following study entry. Multivariate analysis determined that the change in BMD was positively associated with baseline alkaline phosphatase and creatinine clearance and negatively associated with baseline BMD. BMD improves with GC withdrawal after renal transplantation, and this gain in BMD is dependent on the baseline bone turnover, renal function, and BMD.

  13. 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.

  14. 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

  15. Optimal management of bone mineral disorders in chronic kidney disease and ESRD

    PubMed Central

    Lundquist, Andrew L.; Nigwekar, Sagar U.

    2016-01-01

    Purpose of review This review summarizes recent studies on chronic kidney disease-mineral bone disorders, with a focus on new developments in disease management. Recent findings The term chronic kidney disease-mineral bone disorder has come to describe an increasingly complex network of alterations in minerals and skeletal disorders that contribute to the significant cardiovascular morbidity and mortality seen in patients with chronic kidney disease and ESRD. Clinical studies continue to suggest associations with clinical outcomes, yet current clinical trials have failed to support causality. Variability in practice exists as current guidelines for management of bone-mineral disorders are often based on weak evidence. Recent studies implicate novel pathways for therapeutic intervention in clinical trials. Summary Mineral-bone disorders in chronic kidney disease arise from alterations in a number of molecules in an increasingly complex physiological network interconnecting bone and the cardiovascular system. Despite extensive associations with improved outcomes in a number of molecules, clinical trials have yet to prove causality and there is an absence of new therapies available to improve patient outcomes. Additional clinical trials that can incorporate the complexity of mineral bone disorders and with the ability to intervene on more than one pathway are needed to advance patient care. PMID:26785065

  16. Optimal management of bone mineral disorders in chronic kidney disease and end stage renal disease.

    PubMed

    Lundquist, Andrew L; Nigwekar, Sagar U

    2016-03-01

    The review summarizes recent studies on chronic kidney disease-mineral bone disorders, with a focus on new developments in disease management. The term chronic kidney disease-mineral bone disorder has come to describe an increasingly complex network of alterations in minerals and skeletal disorders that contribute to the significant cardiovascular morbidity and mortality seen in patients with chronic kidney disease and end stage renal disease. Clinical studies continue to suggest associations with clinical outcomes, yet current clinical trials have failed to support causality. Variability in practice exists as current guidelines for management of mineral bone disorders are often based on weak evidence. Recent studies implicate novel pathways for therapeutic intervention in clinical trials. Mineral bone disorders in chronic kidney disease arise from alterations in a number of molecules in an increasingly complex physiological network interconnecting bone and the cardiovascular system. Despite extensive associations with improved outcomes in a number of molecules, clinical trials have yet to prove causality and there is an absence of new therapies available to improve patient outcomes. Additional clinical trials that can incorporate the complexity of mineral bone disorders, and with the ability to intervene on more than one pathway, are needed to advance patient care.

  17. Intrarenal cells, not bone marrow–derived cells, are the major source for regeneration in postischemic kidney

    PubMed Central

    Lin, Fangming; Moran, Ashley; Igarashi, Peter

    2005-01-01

    Ischemic injury to the kidney produces acute tubular necrosis and apoptosis followed by tubular regeneration and recovery of renal function. Although mitotic cells are present in the tubules of postischemic kidneys, the origins of the proliferating cells are not known. Bone marrow cells (BMCs) can differentiate across lineages to repair injured organs, including the kidney. However, the relative contribution of intrarenal cells and extrarenal cells to kidney regeneration is not clear. We produced transgenic mice that expressed enhanced GFP (EGFP) specifically and permanently in mature renal tubular epithelial cells. Following ischemia/reperfusion injury (IRI), EGFP-positive cells showed incorporation of BrdU and expression of vimentin, which provides direct evidence that the cells composing regenerating tubules are derived from renal tubular epithelial cells. In BMC-transplanted mice, 89% of proliferating epithelial cells originated from host cells, and 11% originated from donor BMCs. Twenty-eight days after IRI, the kidneys contained 8% donor-derived cells, of which 8.4% were epithelial cells, 10.6% were glomerular cells, and 81% were interstitial cells. No renal functional improvement was observed in mice that were transplanted with exogenous BMCs. These results show that intrarenal cells are the main source of renal repair, and a single injection of BMCs does not make a significant contribution to renal functional or structural recovery. PMID:16007252

  18. P2Y receptors and kidney function

    PubMed Central

    Stockand, James; Rieg, Timo

    2012-01-01

    Cellular release of nucleotides is of physiological importance to regulate and maintain cell function and integrity. Also in the tubular and collecting duct system of the kidney, nucleotides are released in response to changes in cell volume or luminal flow rate and act in a paracrine and autocrine way on basolateral and luminal P2Y receptors. Recent studies using gene knockout mice assigned a prominent role to G protein-coupled P2Y2 receptors, which are activated by both ATP and UTP. The antidiuretic hormone, arginine-vasopressin (AVP), and possibly an increase in collecting duct cell volume induce ATP release. The subsequent activation of P2Y2 receptors inhibits AVP-induced cAMP formation and water reabsorption, which stabilizes cell volume and facilitates water excretion. An increase in NaCl intake enhances luminal release of ATP and UTP in the aldosterone-sensitive distal nephron which by activating apical P2Y2 receptors and phospholipase C lowers the open probability of the epithelial sodium channel ENaC, thereby facilitating sodium excretion. Thus, the renal ATP/UTP/P2Y2 receptor system not only serves to preserve cell volume and integrity but is also regulated by stimuli that derive from body NaCl homeostasis. The system also inhibits ENaC activity during aldosterone escape, i.e. when sodium reabsorption via ENaC is inappropriately high. The P2Y2 receptor tone inhibits the expression and activity of the Na-K-2Cl cotransporter NKCC2 in the thick ascending limb and mediates vasodilation. While the role of other P2Y receptors in the kidney is less clear, the ATP/UTP/P2Y2 receptor system regulates NaCl and water homeostasis and blood pressure. PMID:23145369

  19. Bone is Not Alone: the Effects of Skeletal Muscle Dysfunction in Chronic Kidney Disease.

    PubMed

    Avin, Keith G; Moorthi, Ranjani N

    2015-06-01

    Chronic kidney disease (CKD) is associated with a decline in muscle mass, strength, and function, collectively called "sarcopenia." Sarcopenia is associated with hospitalizations and mortality in CKD and is therefore important to understand and characterize. While the focus of skeletal health in CKD has traditionally focused on bone and mineral aberrations, it is now recognized that sarcopenia must also play a role in poor musculoskeletal health in this population. In this paper, we present an overview of skeletal muscle changes in CKD, including defects in skeletal muscle catabolism and anabolism in uremic tissue. There are many gaps in knowledge in this field that should be the focus for future research to unravel pathogenesis and therapies for musculoskeletal health in CKD.

  20. [Kidney and bone update : the 5-year history and future of CKD-MBD. Bisphosphonates treatment for chronic kidney disease-mineral and bone disorder].

    PubMed

    Mori, Hiroko; Okada, Yosuke; Tanaka, Yoshiya; Hashimoto, Osamu

    2012-07-01

    Recently, much of the attention given to bone-mineral disorder as the prognostic factor for mortality has focused on their links to chronic-kidney disease. High-frequency severe atherosclerosis/calcinosis is observed in chronic dialysis, which leads to cardiovascular events. Recent progress in basic research has revealed certain similarities between processes of bone calcification and calcifications of vascular tissues which contribute to several cardiovascular diseases. However, the effective treatment for suppressing the progression of vascular calcification has not been established. Here we review the mechanism of vascular calcification and present our findings that a bisphosphonate is useful in prevention of vascular calcification in chronic renal failure.

  1. When, how, and why a bone biopsy should be performed in patients with chronic kidney disease.

    PubMed

    Torres, Pablo Ureña; Bover, Jordi; Mazzaferro, Sandro; de Vernejoul, Marie Christine; Cohen-Solal, Martine

    2014-11-01

    In chronic kidney disease the excessive production of parathyroid hormone increases the bone resorption rate and leads to histologic bone signs of secondary hyperparathyroidism. However, in other situations, the initial increase in parathyroid hormone and bone remodeling may be slowed down excessively by a multitude of factors including age, ethnic origin, sex, and treatments such as vitamin D, calcium salts, calcimimetics, steroids, and so forth, leading to low bone turnover or adynamic bone disease. Both high and low bone turnover diseases actually are observed equally in chronic kidney disease patients treated by dialysis, and all types of renal osteodystrophy are associated with an increased risk of skeletal fractures, reduced quality of life, and poor clinical outcomes. Unfortunately, the diagnosis of these bone abnormalities cannot be obtained correctly by current clinical, biochemical, and imaging methods. Therefore, bone biopsy has been, and still remains, the gold standard analysis for assessing the exact type of renal osteodystrophy. It is also the unique way to assess the mechanisms of action, safety, and efficacy of new bone-targeting therapies. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. [Diabetic Kidney Disease 3rd stage - laboratory markers of mineral bone disorder].

    PubMed

    Klimentová, Adriana; Ságová, Ivana; Prídavková, Dana; Kantárová, Daniela; Makovický, Pavol; Sadloňová, Jurina; Mokáň, Marián

    Diabetes mellitus is the most common cause of end stage kidney disease in the developed countries. Chronic kidney disease-mineral and bone disorder (CKD-MBD) develops with deteriorating of the renal functions. Diabetic patients on hemodialysis are characterized by low bone turnover, higher prevalence of severe and progressive vascular calcification with increased cardiovascular morbidity and mortality. The main factor which causes vascular calcification in patients with diabetic kidney disease (DKD) is poor glycemic control. The recent trial findings describe an inverse correlation between intact parathyroid hormone (iPTH) serum levels and glycemic control in a group of diabetic patients on hemodialysis. The objective of the proposed project is to access the difference of the laboratory markers MBD in the group of patients with 3rd stage DKD depending on glycemic control. We focused on the relationship between the glycemic compensation of diabetes (HbA1c) and iPTH serum level. Ninety one patients with 3rd stage DKD were investigated. There were 46 women (50.5 %) and 45 men (49.5 %), average age of patients was 71.2 ± 7.0 years, with creatinine level 128 ± 30 μmol/l and estimated glomerular filtration (eGF, MDRD) 0.82 ± 0.16 ml/s. There were 60 patients with better glycemic control of diabetes (HbA1c < 7 %) vs 29 patients with poorly controlled diabetes (HbA1c > 7 %). MBD markers were compared in both groups. Patients were further stratified into subgroups based on the serum level of iPTH (iPTH < 35 pg/ml vs iPTH > 35 pg/ml) and MBD markers compared. Statistical analysis was performed using and Mann-Whitney test. We have found the statistical significance in the serum phosphate and proteinuria levels in between groups with HbA1c < 7 % vs patients with HbA1c > 7 %. Diabetics with better glycemic control had significant reduction in serum phosphate level (1.14 ± 0.20 vs 1.23 ± 0.18 mmol/l, p = 0.038) and in 24 hrs proteinuria level (0.56 ± 1.35 vs 1.30 ± 1

  3. [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Effect of vitamin D on kidney and cardiovascular system].

    PubMed

    Fujii, Hideki

    2010-07-01

    Recently, many investigators have reported that treatment with vitamin D improves outcomes of patients with chronic kidney disease. Though the detailed mechanisms have remained unclear, it has been speculated that such a treatment may prevent progression of chronic kidney disease and cardiovascular disease. It has been reported that Vitamin D may attenuate renal injury and ameliorate renal function and proteinuria. In addition, several studies have shown that vitamin D may prevent progression of atherosclerosis, vascular calcification and left ventricular hypertrophy. The emerging experimental and clinical evidence has suggested that vitamin D may protect kidney and cardiovascular system.

  4. Assessment of bone turnover markers to predict mineral and bone disorder in men with pre-dialysis non-diabetic chronic kidney disease.

    PubMed

    Davina, Joseph Jessy; Priyadarssini, M; Rajappa, Medha; Parameswaran, Sreejith; Sahoo, Jayaprakash; Mohan Raj, P S; Revathy, G; Palanivel, C; Marella, Marie Gilbert

    2017-06-01

    Chronic kidney disease (CKD) is commonly associated with disturbances in mineral metabolism and bone disease. Bone biopsy is the gold standard in diagnosing mineral bone disorder. Hence the search for non-invasive assessment of bone health gains importance. We undertook to assess the bone health in men with stage 4 and 5 chronic kidney Disease. We recruited 32 male subjects with Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25-hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline phosphatase were assayed. Bone mineral density (BMD) was estimated using dual-energy X-ray absorptiometry. CKD is associated with significantly higher levels of bone-specific alkaline phosphatase and intact parathyroid hormone and lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to controls. In the multivariate linear regression model, bone-specific alkaline phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator Characteristic analysis for prediction of reduced BMD in CKD showed both intact parathyroid hormone and bone-specific alkaline phosphatase have significant predicting power. The combination of bone-specific alkaline phosphatase and intact parathyroid hormone has more significant predicting power and is a more reliable index for non-invasive assessment of bone health in men with chronic kidney disease, than either marker when used alone. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Genetic loci influencing kidney function and chronic kidney disease in man

    PubMed Central

    Chambers, John C; Zhang, Weihua; Lord, Graham M; van der Harst, Pim; Lawlor, Debbie A; Sehmi, Joban S; Gale, Daniel P; Wass, Mark N; Ahmadi, Kourosh R; Bakker, Stephan JL; Beckmann, Jacqui; Bilo, Henk JG; Bochud, Murielle; Brown, Morris J; Caulfield, Mark J; Connell, John M C; Cook, Terence; Cotlarciuc, Ioana; Smith, George Davey; de Silva, Ranil; Deng, Guohong; Devuyst, Olivier; Dikkeschei, Lambert D.; Dimkovic, Nada; Dockrell, Mark; Dominiczak, Anna; Ebrahim, Shah; Eggermann, Thomas; Farrall, Martin; Ferrucci, Luigi; Floege, Jurgen; Forouhi, Nita G; Gansevoort, Ron T; Han, Xijin; Hedblad, Bo; van der Heide, Jaap J Homan; Hepkema, Bouke G; Hernandez-Fuentes, Maria; Hypponen, Elina; Johnson, Toby; de Jong, Paul E; Kleefstra, Nanne; Lagou, Vasiliki; Lapsley, Marta; Li, Yun; Loos, Ruth J F; Luan, Jian'an; Luttropp, Karin; Maréchal, Céline; Melander, Olle; Munroe, Patricia B; Nordfors, Louise; Parsa, Afshin; Penninx, Brenda W.; Perucha, Esperanza; Pouta, Anneli; Prokopenko, Inga; Roderick, Paul J; Ruokonen, Aimo; Samani, Nilesh; Sanna, Serena; Schalling, Martin; Schlessinger, David; Schlieper, Georg; Seelen, Marc AJ; Shuldiner, Alan R; Sjögren, Marketa; Smit, Johannes H.; Snieder, Harold; Soranzo, Nicole; Spector, Timothy D; Stenvinkel, Peter; Sternberg, Michael JE; Swaminathan, Ramasamyiyer; Tanaka, Toshiko; Ubink-Veltmaat, Lielith J.; Uda, Manuela; Vollenweider, Peter; Wallace, Chris; Waterworth, Dawn; Zerres, Klaus; Waeber, Gerard; Wareham, Nicholas J; Maxwell, Patrick H; McCarthy, Mark I; Jarvelin, Marjo-Riitta; Mooser, Vincent; Abecasis, Goncalo R; Lightstone, Liz; Scott, James; Navis, Gerjan; Elliott, Paul; Kooner., Jaspal S

    2013-01-01

    Chronic kidney disease (CKD), the result of permanent loss of kidney function, is a major global problem. We identify common genetic variants at chr2p12-p13, chr6q26, chr17q23 and chr19q13 associated with serum creatinine, a marker of kidney function (P=10−10 to 10−15). SNPs rs10206899 (near NAT8, chr2p12-p13) and rs4805834 (near SLC7A9, chr19q13) were also associated with CKD. Our findings provide new insight into metabolic, solute and drug-transport pathways underlying susceptibility to CKD. PMID:20383145

  6. Vitamin D, chronic kidney disease and survival: a pluripotent hormone or just another bone drug?

    PubMed

    Biggar, Patrick H; Liangos, Orfeas; Fey, Holger; Brandenburg, Vincent M; Ketteler, Markus

    2011-01-01

    It is now about 40 years ago that the mechanism of renal 1-α-hydroxylation of vitamin D was discovered and characterized. After this seminal observation, the key role of the active vitamin D derivative 1, 25-(OH)2-vitamin D (calcitriol) in calcium homeostasis and bone mineralization, and its specific role in the course of chronic kidney disease (CKD) and renal osteopathy, was unraveled step by step, while the precursor 25-OH-vitamin D (calcidiol) was gradually ignored. Calcitriol and its synthetic analogue alfa-calcidol became the first-line standard drug to tackle secondary hyperparathyroidism (sHPT) in CKD. Potential side-effects, including hypercalcemia, hyperphosphatemia, and vascular calcification, were partly abrogated by developing less calcemic substances such as paricalcitol or maxacalcitol. Thus, TIME Magazine surprised when nominating vitamin D, with regard to its newly discovered pleiotropic actions, as one of the "top medical breakthroughs" in the December issue of 2007. This vote was driven by novel and spectacular insights into the pivotal regulatory role of vitamin D with regard to autoimmune diseases, immune defense, cancer development and progression, and cardiovascular function and disease. More than 30 cell types express the vitamin D receptor (VDR), and more than ten organs in addition to the kidney are capable of paracrine 1-α-hydroxylation. More than 200 genes are under the control of calcitriol. A MEDLINE search performed in December 2009 focusing on the keywords "vitamin D-and-kidney-and-2009" yielded 523 hits. This review intends to give a subjective and CKD-related update on novel biological and clinical insights with relevance to the steroid hormone vitamin D.

  7. Klotho preservation via histone deacetylase inhibition attenuates chronic kidney disease-associated bone injury in mice

    PubMed Central

    Lin, Wenjun; Li, Yanning; chen, Fang; Yin, Shasha; Liu, Zhihong; Cao, Wangsen

    2017-01-01

    Bone loss and increased fracture are the devastating outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD) resulting from Klotho deficit-related mineral disturbance and hyperparathyroidism. Because Klotho down-regulation after renal injury is presumably affected by aberrant histone deacetylase (HDAC) activities, here we assess whether HDAC inhibition prevents Klotho loss and attenuates the CKD-associated bone complication in a mouse model of CKD-MBD. Mice fed adenine-containing diet developed the expected renal damage, a substantial Klotho loss and the deregulated key factors causally affecting bone remodeling, which were accompanied by a marked reduction of bone mineral density. Intriguingly, administration of a potent HDAC inhibitor trichostatin A (TSA) impressively alleviated the Klotho deficit and the observed alterations of serum, kidney and bone. TSA prevented Klotho loss by increasing the promoter-associated histone acetylation, therefore increasing Klotho transcription. More importantly the mice lacking Klotho by siRNA interference largely abolished the TSA protections against the serum and renal abnormalities, and the deranged bone micro-architectures. Thus, our study identified Klotho loss as a key event linking HDAC deregulation to the renal and bone injuries in CKD-MBD mice and demonstrated the therapeutic potentials of endogenous Klotho restoration by HDAC inhibition in treating CKD and the associated extrarenal complications. PMID:28387374

  8. 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.

  9. [Functionality and osteointegration of bone allografts in long bone osteosarcomas].

    PubMed

    López-Martínez, J J; García-Sandoval, P P; Fernández-Hernández, J A; Valcárcel-Díaz, A

    2012-01-01

    In patients undergoing long bone resection for osteosarcoma the use of bone allografts is a treatment option. How do they behave functionally and what is their long term osteointegration? A retrospective, observational, longitudinal study was conducted to obtain clinical and radiologic data of the sample composed of a group of 15 patients with a diagnosis of limb osteosarcoma treated at our hospital with structural bone allografts. The Mankin and ISOLS (International Symposium on Limb Salvage) scales were applied to assess allograft functionality and osteointegration, respectively, from 1993 to 2006. Functional results were as follows: excellent, 10 patients (66.6%); good, one patient (6.6%), and poor, 4 patients (26%). The osteointegration assessment reported excellent results in 77% of cases at 18 months and in 87% at 2 years. Surgical wound infection was reported as a complication in only 2 patients (13.3%). Functionality and osteointegration in patients undergoing conservative surgery with bone allografts are excellent in most cases, and this is the technique of choice for the treatment of long bone osteosarcomas.

  10. 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

  11. 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

  12. The association of chronic kidney disease-mineral bone disorder and cardiovascular risk.

    PubMed

    Eddington, Helen; Kalra, Philip A

    2010-05-01

    Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as 'renal osteodystrophy' or 'renal bone disease'. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.

  13. Structural and Functional Changes With the Aging Kidney.

    PubMed

    Denic, Aleksandar; Glassock, Richard J; Rule, Andrew D

    2016-01-01

    Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  14. Assessment of kidney function in preterm infants: lifelong implications.

    PubMed

    Abitbol, Carolyn L; DeFreitas, Marissa J; Strauss, José

    2016-12-01

    This educational review will highlight the historical and contemporary references that establish a basic understanding of measurements of kidney function in the neonate and its relevance for the life of an individual. Importantly, the differential renal function of preterm infants relative to term infants has become paramount with the increased viability of preterm infants and the realization that kidney function is associated with gestational age. Moreover, neonatal kidney function is primarily associated with absolute renal mass and hemodynamic stability. Neonatal kidney function and its early developmental progression predict lifelong cardiovascular and renal disease risks. Validation of estimation equations of kidney function in this population has provided important reference data for other investigations and a clinical basis for prospective and longitudinal follow-up. Future research should be directed towards a better understanding of surrogate markers of kidney function from infancy through adulthood. Pediatric nephrologists should be aware of the developmental aspects of kidney function including the importance of the congenital nephron endowment and the preservation of kidney function throughout a lifetime. • Nephrogenesis occurs in utero in concert with other organ systems by branching morphogenesis, including the lungs, pancreas, and vascular tree, with over 60 % of nephrons being formed during the last trimester. • Infants born preterm before 36 weeks' gestation are in active nephrogenesis and are at increased risk of having a decreased nephron endowment from prenatal and postnatal genetic and epigenetic hazards that will impact the patient for a lifetime. • Post-natal adaptation of kidney function is directly proportional to the number of perfused nephrons, estimated by total kidney volume (TKV), mean arterial pressure (MAP), and gestational age. • Accurate measurement of glomerular filtration rate (GFR) in infants is problematic due to the

  15. The non-functioning kidney in renal tuberculosis.

    PubMed

    Tabakov, I; Totsev, N; Chervenakov, A

    1976-01-01

    The authors have found a non-functioning kidney in 117 patients, constituting more than 24 per cent of 487 patients with bacteriologically and/or histologically confirmed renal tuberculosis, treated and followed up in the last ten years. In 2/3 of the patients with non-functioning kidney and renal tuberculosis, the conditions of non-functioning had been already present from the very beginning, at the time when renal tuberculosis was established. In the remaining 1/3 of the patients, one of the kidneys had ceased to function in the course of treatment. The authors found that the main causes for the failure of the kidney function in renal tuberculosis are strictures of the draining urinary pathways. Emphasis is laid upon the necessity of a careful observation of the patients with renal tuberculosis in the course of drug treatment in view of a timely detection and treatment ofthe strictures in the draining urinary pathways.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. Bone turnover markers are associated with bone density, but not with fracture in end stage kidney disease: a cross-sectional study.

    PubMed

    Jørgensen, Hanne Skou; Winther, Simon; Bøttcher, Morten; Hauge, Ellen-Margrethe; Rejnmark, Lars; Svensson, My; Ivarsen, Per

    2017-09-06

    Fracture risk is increased in chronic kidney disease (CKD), but assessment of bone fragility remains controversial in these patients. This study investigated the associations between bone turnover markers, bone mineral density (BMD), and prevalent fragility fracture in a cohort of kidney transplantation candidates. Volumetric BMD of spine and hip was measured by quantitative computed tomography. Parathyroid hormone (PTH), bone-specific alkaline phosphatase, procollagen type-1 N-terminal propeptide, tartrate resistant alkaline phosphatase, and C- and N-terminal telopeptides of type 1 collagen were analyzed from fasting morning blood samples. Fragility fractures included prevalent vertebral fractures and previous low-trauma clinical fractures. The fracture prevalence was 18% in 157 adult kidney transplant candidates. Fractured patients had reduced BMD and Z-score at both spine and hip. Levels of bone turnover markers were significantly higher in patients on maintenance dialysis than in pre-dialysis patients; but did not differ between patients with and without fracture. There were strong, positive correlations between PTH and all bone turnover markers. PTH was negatively associated with Z-score at lumbar spine and total hip; in contrast, bone turnover markers were only negatively associated with total hip Z-score. Bone turnover markers were negatively associated with bone density, but not associated with prevalent fracture in kidney transplantation candidates. The role of bone turnover markers in assessing bone fragility in CKD will require further investigation. This study was registered at ClinicalTrials.gov with identifier NCT01344434 .

  1. Renal Function and Bone Loss in a Cohort of Afro-Caribbean Men.

    PubMed

    Kuipers, Allison L; Egwuogu, Heartley; Evans, Rhobert W; Patrick, Alan L; Youk, Ada; Bunker, Clareann H; Zmuda, Joseph M

    2015-12-01

    Poor renal function is associated with increased rates of bone loss and osteoporotic fractures in Caucasian men. The importance of kidney function for skeletal health in African ancestry men, who are a population segment with a high prevalence of chronic kidney disease as well as high peak bone mass, is not well known. We examined the relationship between estimated glomerular filtration rate (eGFR) and rates of bone loss in a large population cohort of otherwise healthy Afro-Caribbean men aged 40 years and older. Dual X-ray absorptiometry of the proximal femur and quantitative computed tomography of the proximal radius and tibia were obtained approximately 6 years apart. We calculated eGFR from serum creatinine that was measured in fasting samples in 1451 men. Impaired kidney function (IKF, eGFR<60 ml/min/1.7 m(2)) was observed in 8.6% of the cohort. The relationship between IKF and baseline BMD and annualized rate of change in BMD was analyzed controlling for potentially important confounders. IKF was not associated with baseline BMD. In contrast, men with IKF experienced a rate of decline in areal BMD at the total hip, femoral neck and trochanter and cortical volumetric BMD compared to those with normal kidney function (p<0.05 for all). Impaired kidney function was not associated with changes in trabecular volumetric BMD. In conclusion, poorer kidney function is associated with accelerated bone loss among otherwise healthy Afro-Caribbean men even after controlling for age and other important medical and lifestyle related variables. © 2015 American Society for Bone and Mineral Research.

  2. 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

  3. 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

  4. Novel in vivo techniques to visualize kidney anatomy and function.

    PubMed

    Peti-Peterdi, János; Kidokoro, Kengo; Riquier-Brison, Anne

    2015-07-01

    Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution, which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment. Comprehensive and quantitative kidney structure and function MPM studies helped our better understanding of the cellular and molecular mechanisms of the healthy and diseased kidney. This review summarizes recent in vivo MPM studies with a focus on the glomerulus and the filtration barrier, although select, glomerulus-related renal vascular and tubular functions are also mentioned. The latest applications of serial MPM of the same glomerulus in vivo, in the intact kidney over several days, during the progression of glomerular disease are discussed. This visual approach, in combination with genetically encoded fluorescent markers of cell lineage, has helped track the fate and function (e.g., cell calcium changes) of single podocytes during the development of glomerular pathologies, and provided visual proof for the highly dynamic, rather than static, nature of the glomerular environment. Future intravital imaging applications have the promise to further push the limits of optical microscopy, and to advance our understanding of the mechanisms of kidney injury. Also, MPM will help to study new mechanisms of tissue repair and regeneration, a cutting-edge area of kidney research.

  5. Structural and functional changes with the aging kidney

    PubMed Central

    Denic, Aleksandar; Glassock, Richard J.; Rule, Andrew D.

    2015-01-01

    Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The micro-anatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macro-anatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous renal cysts. Among carefully-screened healthy kidney donors, glomerular filtration rate declines at a rate of 6.3 ml/min/1.73m2 per decade. There is reason to be concerned that the elderly are being misdiagnosed with chronic kidney disease. Besides this expected kidney function decline, the lowest risk of mortality is at a glomerular filtration rate of ≥75 ml/min/1.73 m2 for age <55 years but at a lower glomerular filtration rate of 45-104 ml/min/1.73m2 for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less renal functional reserve when they do actually develop chronic kidney disease and they are also at higher risk for acute kidney injury. PMID:26709059

  6. Bone Disorders in Chronic Kidney Disease: An Update in Diagnosis and Management.

    PubMed

    Babayev, Revekka; Nickolas, Thomas L

    2015-01-01

    Renal osteodystrophy (ROD) is a bone disorder that occurs in chronic kidney disease (CKD) patients and is associated with 2- to 14-fold increased fracture risk compared to the general population. Risk of fractures is also increased in kidney transplant recipients especially within the first 5 years after transplantation. Fractures in CKD patients are associated with increased morbidity and mortality; thus, proper screening and management of CKD bone complications is critical to improving clinical outcomes. Tetracycline double-labeled transiliac crest bone biopsy with histomorphometry is the gold standard for the diagnosis and classification of ROD. However, bone biopsy is not practical to obtain in all patients. Thus, there is great interest in noninvasive approaches that can be used in the clinic to assess ROD. Here, we discuss the role of surrogate measures of bone health in CKD patients, such as dual energy X-ray absorptiometry (DXA) and novel high-resolution imaging, in conjunction with biochemical biomarkers of bone turnover. Recommended guidelines for diagnosis and management of CKD-MBD are discussed.

  7. A rat model of chronic kidney disease-mineral bone disorder.

    PubMed

    Moe, Sharon M; Chen, Neal X; Seifert, Mark F; Sinders, Rachel M; Duan, Dana; Chen, Xianming; Liang, Yun; Radcliff, J Scott; White, Kenneth E; Gattone, Vincent H

    2009-01-01

    Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) is a newly defined syndrome encompassing patients with chronic kidney disease that have a triad of biochemical alterations in calcium, phosphorus and parathyroid hormone, vascular calcification, and bone abnormalities. Here we describe a novel Cy/+ rat model of slowly progressive kidney disease spontaneously developing the three components of CKD-MBD when fed a normal phosphorus diet. Since the renal disorder progressed 'naturally' we studied the effect of dietary manipulation during the course of the disease. Animals with early, but established, chronic kidney disease were fed a casein-based or a grain-based protein diet both of which had equivalent total phosphorus contents. The two different sources of dietary protein had profound effects on the progression of CKD-MBD, likely due to differences in intestinal bioavailability of phosphorus. Although both dietary treatments resulted in the same serum phosphorous levels, the casein-fed animals had increased urinary phosphorus excretion and elevated serum FGF23 compared to the grain-fed rats. This model should help identify early changes in the course of chronic kidney disease that may lead to CKD-MBD.

  8. Early chronic kidney disease-mineral bone disorder stimulates vascular calcification

    PubMed Central

    Fang, Yifu; Ginsberg, Charles; Sugatani, Toshifumi; Monier-Faugere, Marie-Claude; Malluche, Hartmut; Hruska, Keith A

    2013-01-01

    The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an extremely important complication of kidney diseases. Here we tested whether CKD-MBD causes vascular calcification in early kidney failure by developing a mouse model of early CKD in a background of atherosclerosis stimulated arterial calcification. CKD equivalent in glomerular filtration reduction to human CKD stage 2 stimulated early vascular calcification and inhibited the tissue expression of α-klotho (klotho) in the aorta. In addition, osteoblast transition in the aorta was stimulated by early CKD as shown by the expression of the critical transcription factor, RUNX2. The ligand associated with the klotho-fibroblast growth factor receptor complex, FGF23, was found to be expressed in the vascular media of sham operated mice. Its expression was decreased in early CKD. Increased circulating levels of the osteocyte secreted proteins, FGF23, and sclerostin may have been related to increased circulating klotho levels. Finally, we observed low turnover bone disease with a reduction in bone formation rates more than bone resorption. Thus, the CKD-MBD, characterized by cardiovascular risk factors, vascular calcification, increased circulating klotho, FGF23 and sclerostin levels, and low turnover renal osteodystrophy, was established in early CKD. Early CKD caused a reduction of vascular klotho, stimulated vascular osteoblastic transition, increased osteocytic secreted proteins, and inhibited skeletal modeling producing the CKD-MBD. PMID:23884339

  9. 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

  10. Cardiovascular Risk in Chronic Kidney Disease (CKD), the CKD- Mineral Bone Disorder (CKD- MBD)

    PubMed Central

    Hruska, Keith A.; Choi, Eric T.; Memon, Imran; Davis, T. Keefe; Mathew, Suresh

    2013-01-01

    Recent advances in our understanding of the excess mortality of chronic kidney disease (CKD) due to cardiovascular complications demonstrate through observational studies that vascular calcification and hyperphosphatemia are major cardiovascular risk factors. Mechanistic studies demonstrate that these two risk factors are related, and that hyperphosphatemia directly stimulates vascular calcification. The role of hyperphosphatemia in stimulating vascular calcification in CKD is associated with a block to the skeletal reservoir function in phosphate balance due to excess bone resorption. This has lead to the realization that renal osteodystrophy is linked to vascular calcification by disordered mineral homeostasis (phosphate), and that a multiorgan system fails in CKD leading to cardiovascular mortality. In children with renal disease the multiorgan system fails just as in adults, but the outcomes have been less well studied and perceptions of differences from adults are possibly incorrect. Vascular calcification and cardiovascular mortality are less prevalent but present. However, CKD induced vascular disease causes stiffness of the arterial tree causing systolic hypertension and left ventricular hypertrophy as early manifestations of the same pathology in the adult. Because of the role of the skeleton in these outcomes, renal osteodystrophy has been renamed as the CKD-mineral bone disorder (CKD-MBD). This review adapted to children describes our current state of knowledge with regards to the pathophysiology of the CKD-MBD, including the new discoveries related to early stages of CKD. As a new necessity, cardiovascular function issues are incorporated into the CKD-MBD, and new advances in our knowledge of this critical component of the disorder will lead to improved outcomes in CKD. PMID:19898875

  11. Chronic kidney disease-mineral bone disorder: an update on the pathology and cranial manifestations.

    PubMed

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

    2015-04-01

    Chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome encompassing skeletal and extra skeletal changes associated with chronic kidney disease. It progresses silently until an advanced clinical stage when complications impact on the quality of life and survival rates of patients. The maxillofacial manifestations are unique and may play an important role in the early identification of changes which could influence the management of these patients. The goal of this review is to highlight the maxillofacial features, pathology, and principles of management of CKD-MBD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

    PubMed Central

    Tejwani, Vickram; Qian, Qi

    2013-01-01

    The elderly chronic kidney disease (CKD) population is growing. Both aging and CKD can disrupt calcium (Ca2+) homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD). CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD. PMID:23760058

  13. [Bone metabolism and cardiovascular function update. α-klotho/FGF23 system; a new insight into the field of mineral homeostasis and the pathogeneses of aging-associated syndromes and the complications of chronic kidney disease].

    PubMed

    Nabeshima, Yo Ichi

    2014-07-01

    α-klotho (α-kl) was first identified as an aging gene and was later shown to be a regulator of mineral homeostasis. α-kl (- / -) mice display multiple aging related phenotypes including atherosclerosis, cardiovascular/soft tissue calcifications, pulmonary emphysema, osteopenia, and senile atrophy of skin ; such age-related organ pathologies are associated with biochemical changes in blood, including severe hyperphosphatemia, elevated serum FGF23 and1,25 (OH) 2 Vitamin D levels. Of significance, advanced stage patients suffering chronic kidney disease (CKD) develop multiple complications quite resembling phenotypes observed in α-kl (- / -) mice, and high serum phosphate, the major cause of abnormalities of α-kl (- / -) mice, has been reported to be closely associated with high levels of cardiovascular disease morbidity and mortality in patients with CKD, particularly in patients with end-stage renal disease. In addition, the expressions of α-kl mRNA and α-Kl protein were severely reduced in these patients. These results suggest the involvement of α-Kl and FGF23 in the pathogeneses of not only aging-associated syndromes but also the complications of CKD. Here, the unveiling of the molecular functions of α-Klotho and FGF23 has recently given new insight into the field of mineral homeostasis and the pathogeneses of aging-associated syndromes and the complications of CKD.

  14. Functional behaviour of bone around dental implants.

    PubMed

    Stanford, Clark M; Schneider, Galen B

    2004-06-01

    Achieving a long-term stable implant interface is a significant clinical issue when there is insufficient cortical bone stabilisation at implant placement. Clinical outcomes studies suggest that the higher risk implants are those placed in compromised cortical bone (thin, porous, etc.) in anatomical sites with minimal existing trabecular bone (characterised as type IV bone). In establishing and maintaining an implant interface in such an environment, one needs to consider the impact of masticatory forces, the response of bone to these forces and the impact of age on the adaptive capacity of bone. These forces, in turn, have the potential to create localised changes in interfacial stiffness through viscoelastic changes at the interface. Changes in bone as a function of age (e.g. localised hypermineralised osteopetrosis and localised areas of osteopenia) will alter the communication between osteocytes and osteoblasts creating the potential for differences in response of osteoblastic cells in the older population. A key to understanding the biomechanical and functional behaviour of implants in the older population is to control the anticipated modelling and remodelling behaviour through implant design that takes into account how tissues respond to the mechanically active environment.

  15. Concentrations of lead in liver, kidney, and bone of bald and golden eagles.

    PubMed

    Wayland, M; Neugebauer, E; Bollinger, T

    1999-08-01

    The diagnosis of lead poisoning in eagles relies on autopsy information and residue analysis of lead in certain tissues, usually liver or blood. Similarly, the assessment of elevated lead exposure in eagles depends on the determination of lead concentrations in these tissues. Renal and bone lead concentrations have rarely been examined in eagles. We examined relationships among hepatic, renal, and bone lead concentrations in bald and golden eagles from the Canadian prairie provinces. Hepatic and renal lead concentrations were strongly related (R2 = 0.87) while those in liver and bone were significantly but poorly related (R2 = 0.22). Renal lead concentrations of 5 and 18 microg x g-1 (dry weight) corresponded to hepatic lead concentrations of 6 and 30 microg x g-1, the hepatic concentrations that we used as criterion levels associated with elevated lead exposure and death from lead poisoning, respectively. Lead was elevated in 19 of 119 and 21 of 109 liver and kidney samples, respectively. Of these 19 and 21 liver and kidney samples, 14 and 11, respectively, had lead concentrations compatible with death from lead poisoning. Taken together, lead concentrations were elevated in liver or kidney samples from 25 eagles and were compatible with death from lead poisoning in 15. Mean bone lead was higher in eagles with elevated hepatic lead than in those exhibiting background hepatic lead concentrations. However, even in the former group, bone lead concentrations were lower than those in lead-exposed individuals of other species of birds. Bone is probably not a useful tissue for identifying elevated lead exposure in eagles. Three of eleven birds that had been shot had anomalous renal lead concentrations, suggestive of contamination by residue from lead ammunition. It is important to exclude such birds when assessing lead exposure.http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p267.html

  16. Combined Bone Marrow and Kidney Transplantation for the Induction of Specific Tolerance

    PubMed Central

    Chen, Yi-Bin; Kawai, Tatsuo; Spitzer, Thomas R.

    2016-01-01

    The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy after organ transplantation, has been considered the “Holy Grail” of transplantation. Experimentally, tolerance has been achieved through clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the establishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance has been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and kidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism. Combined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions can be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an underlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor hematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve organ transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been successful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the achievement of specific tolerance may become more widely applicable. PMID:27239198

  17. [Treatment of bone disease in chronic kidney disease and in renal transplant recipients under K/DOQI clinical practice guidelines].

    PubMed

    Tokumoto, Tadahiko; Tanabe, Kazunari; Toma, Hiroshi; Akiba, Takashi

    2004-05-01

    The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) provides evidence based clinical practice guidelines developed for all phases of kidney disease and related complications, from diagnosis to monitoring and management. Bone disease sets in during the early stages of Chronic Kidney Disease (CKD). Bone disease is observed in almost patients with chronic renal failure and after renal transplantation. Hyperparathyroid (high turnover) bone disease in patients with chronic renal failure is found most frequently followed by mixed osteodystrophy, low-turn over bone disease, and osteomalasia. Ninety to one hundred percent of kidney transplant patients have histological evidence of osteodystrophy and osteopenia (reduction of bone mass) following renal transplantation. Furthermore, osteoporosis is also appeared in many renal transplant recipients. After renal transplantation, renal osteodystrophy generally improves but bone mineral density (BMD) often worsens. When renal bone disease is assessed using a combination of biochemical markers, histology and bone densitometry, early intervention and carefully effective therapies might be reduced the morbidity associated with these common problems.

  18. Acute graft-versus-host disease of the kidney in allogeneic rat bone marrow transplantation.

    PubMed

    Higo, Seiichiro; Shimizu, Akira; Masuda, Yukinari; Nagasaka, Shinya; Kajimoto, Yusuke; Kanzaki, Go; Fukui, Megumi; Nagahama, Kiyotaka; Mii, Akiko; Kaneko, Tomohiro; Tsuruoka, Shuichi

    2014-01-01

    Allogeneic hematopoietic cell or bone marrow transplantation (BMT) causes graft-versus-host-disease (GVHD). However, the involvement of the kidney in acute GVHD is not well-understood. Acute GVHD was induced in Lewis rats (RT1l) by transplantation of Dark Agouti (DA) rat (RT1(a)) bone marrow cells (6.0 × 10(7) cells) without immunosuppression after lethal irradiation (10 Gy). We examined the impact of acute GVHD on the kidney in allogeneic BMT rats and compared them with those in Lewis-to-Lewis syngeneic BMT control and non-BMT control rats. In syngeneic BMT and non-BMT control rats, acute GVHD did not develop by day 28. In allogeneic BMT rats, severe acute GVHD developed at 21-28 days after BMT in the skin, intestine, and liver with decreased body weight (>20%), skin rush, diarrhea, and liver dysfunction. In the kidney, infiltration of donor-type leukocytes was by day 28. Mild inflammation characterized by infiltration of CD3(+) T-cells, including CD8(+) T-cells and CD4(+) T-cells, and CD68(+) macrophages to the interstitium around the small arteries was noted. During moderate to severe inflammation, these infiltrating cells expanded into the peritubular interstitium with peritubular capillaritis, tubulitis, acute glomerulitis, and endarteritis. Renal dysfunction also developed, and the serum blood urea nitrogen (33.9 ± 4.7 mg/dL) and urinary N-acetyl-β-D-glucosaminidase (NAG: 31.5 ± 15.5 U/L) levels increased. No immunoglobulin and complement deposition was detected in the kidney. In conclusion, the kidney was a primary target organ of acute GVHD after BMT. Acute GVHD of the kidney was characterized by increased levels of urinary NAG and cell-mediated injury to the renal microvasculature and renal tubules.

  19. The potential use of antisclerostin therapy in chronic kidney disease-mineral and bone disorder.

    PubMed

    Costa, Aline G; Bilezikian, John P; Lewiecki, E Michael

    2015-07-01

    Sclerostin is a regulator of the osteoanabolic canonical Wnt signaling pathway, and thus helps to govern rates of bone formation. The Wnt pathway is also recognized as playing an important role in the pathophysiology of the chronic kidney disease-mineral and bone disorder (CKD-MBD). It also may serve as an interface between bone and the vascular system. Pharmacological inhibition of sclerostin has shown promise as an osteoanabolic approach to the treatment of osteoporosis. Inhibition of sclerostin is a potentially useful but unproven strategy in the management of CKD-MBD. Clinical trials with humanized monoclonal sclerostin antibodies (Scl-Ab) have shown a rapid initial increase in bone formation and a marked increase in bone mineral density. Although clinical data, to this point, in CKD are not available, animal models of low bone turnover CKD show that Scl-Ab improves trabecular bone volume and mineralization without affecting biochemical indices. Targeted clinical trials are needed to evaluate the potential effectiveness of Scl-Ab in CKD. Based upon the available data, there is potential not only for this new therapeutic class to improve skeletal health but perhaps also to have substantial cardiovascular benefits in CKD.

  20. Dietary phosphorus excess: a risk factor in chronic bone, kidney, and cardiovascular disease?

    PubMed

    Uribarri, Jaime; Calvo, Mona S

    2013-09-01

    There is growing evidence in the nephrology literature supporting the deleterious health effect of excess dietary phosphorus intake. This issue has largely escaped the attention of nutrition experts until this symposium, which raised the question of whether the same health concerns should be extended to the general population. The potential hazard of a high phosphorus intake in the healthy population is illustrated by findings from acute and epidemiologic studies. Acute studies in healthy young adults demonstrate that phosphorus intakes in excess of nutrient needs may significantly disrupt the hormonal regulation of phosphorus contributing to disordered mineral metabolism, vascular calcification, bone loss, and impaired kidney function. One of the hormonal factors acutely affected by dietary phosphorus loading is fibroblast growth factor-23, which may be a key factor responsible for many of the cardiovascular disease (CVD) complications of high phosphorus intake. Increasingly, large epidemiological studies suggest that mild elevations of serum phosphorus within the normal range are associated with CVD risk in healthy populations. Few population studies link high dietary phosphorus intake to mild changes in serum phosphorus due to study design issues specific to phosphorus and inaccurate nutrient composition databases. The increasing phosphorus intake due to the use of phosphorus-containing ingredients in processed food and the growing consumption of processed convenience and fast foods is an important factor that needs to be emphasized.

  1. Dietary Phosphorus Excess: A Risk Factor in Chronic Bone, Kidney, and Cardiovascular Disease?123

    PubMed Central

    Uribarri, Jaime; Calvo, Mona S.

    2013-01-01

    There is growing evidence in the nephrology literature supporting the deleterious health effect of excess dietary phosphorus intake. This issue has largely escaped the attention of nutrition experts until this symposium, which raised the question of whether the same health concerns should be extended to the general population. The potential hazard of a high phosphorus intake in the healthy population is illustrated by findings from acute and epidemiologic studies. Acute studies in healthy young adults demonstrate that phosphorus intakes in excess of nutrient needs may significantly disrupt the hormonal regulation of phosphorus contributing to disordered mineral metabolism, vascular calcification, bone loss, and impaired kidney function. One of the hormonal factors acutely affected by dietary phosphorus loading is fibroblast growth factor-23, which may be a key factor responsible for many of the cardiovascular disease (CVD) complications of high phosphorus intake. Increasingly, large epidemiological studies suggest that mild elevations of serum phosphorus within the normal range are associated with CVD risk in healthy populations. Few population studies link high dietary phosphorus intake to mild changes in serum phosphorus due to study design issues specific to phosphorus and inaccurate nutrient composition databases. The increasing phosphorus intake due to the use of phosphorus-containing ingredients in processed food and the growing consumption of processed convenience and fast foods is an important factor that needs to be emphasized. PMID:24038251

  2. Kidney Function in Severely Obese Adolescents Undergoing Bariatric Surgery

    PubMed Central

    Xiao, Nianzhou; Jenkins, Todd M; Nehus, Edward; Inge, Thomas H; Michalsky, Marc P; Harmon, Carroll M.; Helmrath, Michael A.; Brandt, Mary L.; Courcoulas, Anita; Moxey-Mims, Marva; Mitsnefes, Mark M

    2014-01-01

    Objective To describe objective measures of kidney function and analyze factors associated with kidney dysfunction in severely obese adolescents undergoing weight loss surgery. Design and Methods We analyzed cross-sectional data from 242 adolescent participants in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study before weight loss surgery. Kidney status was assessed by measuring urine albumin creatinine ratio to determine microalbuminuria and by calculating serum cystatin C-based estimated glomerular filtration rate (eGFR) to assess kidney function. Results Mean age and median body mass index (BMI) were 17.1 years and 50.5kg/m2, respectively; 76% were females and 65% were non-Hispanic white race. Fourteen percent of the cohort had microalbuminuria, and 3% had macroalbuminuria; 3% had eGFR <60 ml/min/1.73m2, and 7.1% had eGFR >150 ml/min/1.73m2. In adjusted analyses, female gender and increasing ferritin levels were significantly associated with the presence of microalbuminuria/macroalbuminuria. Increasing BMI and HOMA-IR values were significantly associated with lower eGFR. Conclusions A significant number of severely obese adolescents undergoing weight loss surgery have evidence of early kidney dysfunction. Longitudinal studies following weight loss surgery in these individuals are needed to determine whether these kidney abnormalities are reversible following weight loss therapy. PMID:25376399

  3. Multiple kidney cysts in thin basement membrane disease with proteinuria and kidney function impairment

    PubMed Central

    Sevillano, Angel M.; Gutierrez, Eduardo; Morales, Enrique; Hernandez, Eduardo; Molina, Maria; Gonzalez, Ester; Praga, Manuel

    2014-01-01

    Background Some patients with thin basement membrane disease (TBMD) develop proteinuria, hypertension and different degrees of CKD, besides the persistent microhaematuria characteristic of the disease. Little is known about factors associated with this unfavourable outcome. Methods We reviewed clinical, pathological and radiological features of 32 patients with biopsy-proven TBMD. Patients were divided in two groups: those with persistent normal kidney function and negative or minimal proteinuria (n = 16) and those with persistent proteinuria >0.5 g/day (n = 16). Results Patients with proteinuria had a worse kidney function at baseline than those with negative proteinuria. Global or segmental glomerulosclerosis, together with interstitial fibrosis, was found in 37% of patients with proteinuria. All proteinuric patients were treated with renin–angiotensin system blockers. At the end of follow-up (198 months in proteinuric patients and 210 months in patients with negative proteinuria) the prevalence of hypertension was 68% in proteinuric patients (12% at baseline), compared with 12 and 6%, respectively, in non-proteinuric patients. A slow decline of renal function was observed in proteinuric patients, although no patient developed end-stage kidney disease. Ultrasound studies showed bilateral kidney cysts in nine patients (56%) with proteinuria. Cysts were bilateral and countless in six patients, and bilateral but with a limited number of cysts in the three remaining patients. No cysts were found in patients with negative proteinuria. Conclusions Some patients with TBMD develop hypertension, proteinuria and CKD. Multiple bilateral kidney cysts were found in a majority (56%) of these patients. Further studies are needed to investigate the pathogenesis and the influence on long-term outcome of this TBMD-associated multiple kidney cysts. PMID:25852885

  4. Renal functional reserve and renal recovery after acute kidney injury.

    PubMed

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use.

  5. 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.

  6. Associations of deceased donor kidney injury with kidney discard and function after transplantation.

    PubMed

    Hall, I E; Schröppel, B; Doshi, M D; Ficek, J; Weng, F L; Hasz, R D; Thiessen-Philbrook, H; Reese, P P; Parikh, C R

    2015-06-01

    Deceased donor kidneys with acute kidney injury (AKI) are often discarded due to fear of poor outcomes. We performed a multicenter study to determine associations of AKI (increasing admission-to-terminal serum creatinine by AKI Network stages) with kidney discard, delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). In 1632 donors, kidney discard risk increased for AKI stages 1, 2 and 3 (compared to no AKI) with adjusted relative risks of 1.28 (1.08-1.52), 1.82 (1.45-2.30) and 2.74 (2.0-3.75), respectively. Adjusted relative risk for DGF also increased by donor AKI stage: 1.27 (1.09-1.49), 1.70 (1.37-2.12) and 2.25 (1.74-2.91), respectively. Six-month eGFR, however, was similar across AKI categories but was lower for recipients with DGF (48 [interquartile range: 31-61] vs. 58 [45-75] ml/min/1.73m(2) for no DGF, p < 0.001). There was significant favorable interaction between donor AKI and DGF such that 6-month eGFR was progressively better for DGF kidneys with increasing donor AKI (46 [29-60], 49 [32-64], 52 [36-59] and 58 [39-71] ml/min/1.73m(2) for no AKI, stage 1, 2 and 3, respectively; interaction p = 0.05). Donor AKI is associated with kidney discard and DGF, but given acceptable 6-month allograft function, clinicians should consider cautious expansion into this donor pool.

  7. Association of Metabolic Syndrome With Kidney Function and Histology in Living Kidney Donors

    PubMed Central

    Ohashi, Y.; Thomas, G.; Nurko, S.; Stephany, B.; Fatica, R.; Chiesa, A.; Rule, A. D.; Srinivas, T.; Schold, J. D.; Navaneethan, S. D.; Poggio, E. D.

    2013-01-01

    The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m2 instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome. PMID:23865821

  8. Berberine improves kidney function in diabetic mice via AMPK activation.

    PubMed

    Zhao, Long; Sun, Li-Na; Nie, Hui-Bin; Wang, Xue-Ling; Guan, Guang-Ju

    2014-01-01

    Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPKα2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice.

  9. Urinary Markers of Kidney Injury and Kidney Function Decline in HIV-Infected Women

    PubMed Central

    Shlipak, Michael G.; Scherzer, Rebecca; Abraham, Alison; Tien, Phyllis C.; Grunfeld, Carl; Peralta, Carmen A.; Devarajan, Prasad; Bennett, Michael; Butch, Anthony W.; Anastos, Kathryn; Cohen, Mardge H.; Nowicki, Marek; Sharma, Anjali; Young, Mary A.; Sarnak, Mark J.; Parikh, Chirag R.

    2012-01-01

    Objective HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women. Methods In the Women's Interagency HIV Study (WIHS), we measured concentrations of albumin-to-creatinine ratio (ACR), interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) from stored urine among 908 HIV-infected and 289 uninfected participants. Primary analyses used cystatin C based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and two follow-up visits over eight years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes. Results Compared with the lowest tertiles, the highest tertiles of ACR (−0.15ml/min/1.73m2, p<0.0001), IL-18 (−0.09ml/min/1.73m2, p<0.0001) and KIM-1 (−0.06ml/min/1.73m2, p<0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all three biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (Relative Risk 1.40; 95%CI 1.04-1.89); ≥5% (1.88; 1.30-2.71); and ≥10% (2.16; 1.20-3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25-2.33) and 10% (1.78; 1.07-2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00-3.87). Conclusions Among HIV-infected women in the WIHS cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function. PMID:23023103

  10. Novel in vivo techniques to visualize kidney anatomy and function

    PubMed Central

    Peti-Peterdi, János; Kidokoro, Kengo; Riquier-Brison, Anne

    2015-01-01

    Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment. Comprehensive and quantitative kidney structure and function MPM studies helped our better understanding of the cellular and molecular mechanisms of the healthy and diseased kidney. This review summarizes recent in vivo MPM studies with a focus on the glomerulus and the filtration barrier, although select, glomerulus-related renal vascular and tubular functions are also mentioned. The latest applications of serial MPM of the same glomerulus in vivo, in the intact kidney over several days, during the progression of glomerular disease are discussed. This visual approach, in combination with genetically encoded fluorescent markers of cell lineage, has helped to track the fate and function (e.g. cell calcium changes) of single podocytes during the development of glomerular pathologies, and provided visual proof for the highly dynamic rather than static nature of the glomerular environment. Future intravital imaging applications have the promise to further push the limits of optical microscopy, and to advance our understanding of the mechanisms of kidney injury. Also, MPM will help to study new mechanisms of tissue repair and regeneration, a cutting edge area of kidney research. PMID:25738253

  11. The impact of gut microbiota on kidney function and pathogenesis.

    PubMed

    Mahmoodpoor, Fariba; Rahbar Saadat, Yalda; Barzegari, Abolfazl; Ardalan, Mohammadreza; Zununi Vahed, Sepideh

    2017-09-01

    Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Baseline kidney function as predictor of mortality and kidney disease progression in HIV-positive patients.

    PubMed

    Ibrahim, Fowzia; Hamzah, Lisa; Jones, Rachael; Nitsch, Dorothea; Sabin, Caroline; Post, Frank A

    2012-10-01

    Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression. Observational cohort study. 7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients. Baseline estimated glomerular filtration rate (eGFR). Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m(2) for >3 months) in Cox proportional hazards and competing-risk regression models. Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m(2). Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m(2) remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m(2) was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m(2) and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m(2). The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria. Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  13. Optimising assessment of kidney function when managing localised renal masses.

    PubMed

    Ellis, Robert J; Joshi, Andre; Ng, Keng L; Francis, Ross S; Gobe, Glenda C; Wood, Simon T

    2017-08-07

    Increased early and incidental detection, improved surgical techniques and technological advancement mean that the management of renal mass lesions is constantly evolving. The treatment of choice for renal mass lesions has historically been radical nephrectomy. Partial nephrectomy is now recommended for localised renal masses, owing to favourable renal functional outcomes. Ablative renal surgery confers a significant risk of chronic kidney disease. There are few studies assessing long term outcomes of nephrectomy on renal outcomes, and virtually no studies assessing long term outcomes for less invasive therapies such as ablation. Unless a renal mass is clearly benign on imaging, management decisions will be made with an assumption of malignancy. The content of this review applies to both benign and malignant renal mass lesions. We advocate for improved strategies for kidney function assessment and risk stratification, early targeted referral, and regular screening for chronic kidney disease for all patients after surgery.

  14. Effect of Nigella sativa on the kidney function in rats

    PubMed Central

    Dollah, Mohammad Aziz; Parhizkar, Saadat; Izwan, Mohammad

    2013-01-01

    Objectives: Nigella sativa (N. sativa) is an amazing herb which is used in traditional medicine for a wide range of illnesses including bronchial asthma, dysentery, gastrointestinal problems, as well as beneficial effect on blood lipids, lowering blood pressure, serum cholesterol, and triglycerides level. This study aimed to determine the toxic effect of N. sativa powder on the kidney function which was evaluated by serum urea and creatinine and through histopathological examination of kidney tissue. Methods and Materials: In this study, 24 male Sprague Dawley rats were randomly divided into four groups (six each). The rats were kept in the separate cage with three rats per cage. The treatment groups were given rat pellet containing N. sativa dose at 0.01, 0.10, and 1.00 g/kg body weight which were considered as low, normal, and high dose for five weeks while control group fed with rat chow pellet without supplementation. At the end of 35 days, the rats were sacrificed to take the blood sample and to remove the kidney organ for toxicity evaluation. Statistical analyses were done through one-way ANOVA using SPSS. Results: The finding revealed that there was no significant difference in serum urea of treatment groups compared with the control group. The results showed a significant decline in serum creatinine of high dose of Nigella sativa treated compared with low dose treated and control groups (p<0.05). Histopathological examination of kidney tissue showed normal kidney architecture with no tissue degeneration, inflammation, necrosis, and tubular dilation in all groups. Conclusion: With the evidence of normal urea and creatinine level in blood and normal kidney tissue in histology examination for all treatment groups, it is suggested that there is no toxic effect on kidney function of Nigella sativa at different doses for five-week period. PMID:25050269

  15. 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.

  16. Multiple New Loci Associated with Kidney Function and Chronic Kidney Disease: The CKDGen consortium

    PubMed Central

    Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian; Olden, Matthias; Glazer, Nicole L.; Parsa, Afshin; Gao, Xiaoyi; Yang, Qiong; Smith, Albert V.; O’Connell, Jeffrey R.; Li, Man; Schmidt, Helena; Tanaka, Toshiko; Isaacs, Aaron; Ketkar, Shamika; Hwang, Shih-Jen; Johnson, Andrew D.; Dehghan, Abbas; Teumer, Alexander; Paré, Guillaume; Atkinson, Elizabeth J.; Zeller, Tanja; Lohman, Kurt; Cornelis, Marilyn C.; Probst-Hensch, Nicole M.; Kronenberg, Florian; Tönjes, Anke; Hayward, Caroline; Aspelund, Thor; Eiriksdottir, Gudny; Launer, Lenore; Harris, Tamara B.; Rapmersaud, Evadnie; Mitchell, Braxton D.; Boerwinkle, Eric; Struchalin, Maksim; Cavalieri, Margherita; Singleton, Andrew; Giallauria, Francesco; Metter, Jeffery; de Boer, Ian; Haritunians, Talin; Lumley, Thomas; Siscovick, David; Psaty, Bruce M.; Zillikens, M. Carola; Oostra, Ben A.; Feitosa, Mary; Province, Michael; Levy, Daniel; de Andrade, Mariza; Turner, Stephen T.; Schillert, Arne; Ziegler, Andreas; Wild, Philipp S.; Schnabel, Renate B.; Wilde, Sandra; Muenzel, Thomas F.; Leak, Tennille S; Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann, H.-Erich; Koenig, Wolfgang; Zgaga, Lina; Zemunik, Tatijana; Kolcic, Ivana; Minelli, Cosetta; Hu, Frank B.; Johansson, Åsa; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Schreiber, Stefan; Aulchenko, Yurii S; Rivadeneira, Fernando; Uitterlinden, Andre G; Hofman, Albert; Imboden, Medea; Nitsch, Dorothea; Brandstätter, Anita; Kollerits, Barbara; Kedenko, Lyudmyla; Mägi, Reedik; Stumvoll, Michael; Kovacs, Peter; Boban, Mladen; Campbell, Susan; Endlich, Karlhans; Völzke, Henry; Kroemer, Heyo K.; Nauck, Matthias; Völker, Uwe; Polasek, Ozren; Vitart, Veronique; Badola, Sunita; Parker, Alexander N.; Ridker, Paul M.; Kardia, Sharon L. R.; Blankenberg, Stefan; Liu, Yongmei; Curhan, Gary C.; Franke, Andre; Rochat, Thierry; Paulweber, Bernhard; Prokopenko, Inga; Wang, Wei; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Shlipak, Michael G.; van Duijn, Cornelia M.; Borecki, Ingrid; Krämer, Bernhard K.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Witteman, Jacqueline C.; Pramstaller, Peter P.; Rettig, Rainer; Hastie, Nick; Chasman, Daniel I.; Kao, W. H.; Heid, Iris M.; Fox, Caroline S.

    2010-01-01

    Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 Caucasian individuals from 20 population-based studies to identify new susceptibility loci for reduced renal function, estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea <60 ml/min/1.73m2; n = 5,807 CKD cases). Follow-up of the 23 genome-wide significant loci (p<5×10−8) in 22,982 replication samples identified 13 novel loci for renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2, and SLC7A9) and 7 creatinine production and secretion loci (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72, BCAS3). These results further our understanding of biologic mechanisms of kidney function by identifying loci potentially influencing nephrogenesis, podocyte function, angiogenesis, solute transport, and metabolic functions of the kidney. PMID:20383146

  17. Bone marrow fat is increased in chronic kidney disease by magnetic resonance spectroscopy

    PubMed Central

    Fadel, W.; Eckert, G. J.; Ponsler-Sipes, K.; Moe, S. M.; Lin, C.

    2015-01-01

    Summary In aging, the bone marrow fills with fat and this may lead to higher fracture risk. We show that a bone marrow fat measurement by magnetic resonance spectroscopy (MRS), a newer technique not previously studied in chronic kidney disease (CKD), is useful and reproducible. CKD patients have significantly higher bone marrow fat than healthy adults. Introduction Renal osteodystrophy leads to increased morbidity and mortality in patients with CKD. Traditional bone biopsy histomorphometry is used to study abnormalities in CKD, but the bone marrow, the source of osteoblasts, has not been well characterized in patients with CKD. Methods To determine the repeatability of bone marrow fat fraction assessment by MRS and water-fat imaging (WFI) at four sites in patients with CKD, testing was performed to determine the coefficients of reproducibility and intraclass coefficients (ICCs). We further determined if this noninvasive technique could be used to determine if there are differences in the percent bone marrow fat in patients with CKD compared to matched controls using paired t tests. Results The mean age of subjects with CKD was 59.8±7.2 years, and the mean eGFR was 24±8 ml/min. MRS showed good reproducibility at all sites in subjects with CKD and controls, with a coefficient of reproducibilities ranging from 2.4 to 13 %. MRS and WFI assessment of bone marrow fat showed moderate to strong agreement (ICC 0.6–0.7) at the lumbar spine, with poorer agreement at the iliac crest and no agreement at the tibia. The mean percent bone marrow fat at L2–L4 was 13.8 % (95 % CI 8.3–19.7) higher in CKD versus controls (p<0.05). Conclusions MRS is a useful and reproducible technique to study bone marrow fat in CKD. Patients with CKD have significantly higher bone marrow fat than healthy adults; the relationship with bone changes requires further analyses. PMID:25701052

  18. Prenatal lead exposure and childhood blood pressure and kidney function.

    PubMed

    Skröder, Helena; Hawkesworth, Sophie; Moore, Sophie E; Wagatsuma, Yukiko; Kippler, Maria; Vahter, Marie

    2016-11-01

    Exposure to lead, a common environmental pollutant, is known to cause cardiovascular and nephrotoxic effects in adults. Potential effects of early-life lead exposure on these functions are, however, less well characterized. To assess blood pressure and kidney function in preschool-aged children in relation to prenatal lead exposure. This prospective study in rural Bangladesh measured children's systolic and diastolic blood pressure in triplicate at the follow-up at 4.5±0.11 years. Their kidney function was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum cystatin C concentrations, and by kidney volume, measured by sonography. Exposure to lead was assessed by concentrations in the mothers' blood (erythrocyte fraction; Ery-Pb) in gestational weeks (GW) 14 and 30, the effects of which were evaluated separately in multivariable-adjusted linear regression analyses. We found no associations between maternal exposure to lead [n~1500 for GW14 and 700 for GW30] and children's blood pressure or eGFR. However, we found an inverse association between late gestation lead and kidney volume, although the sample size was limited (n=117), but not with early gestation lead (n=573). An increase of 85µg/kg in Ery-Pb (median concentration at GW30) was associated with a 6.0cm(3)/m(2) decrease in kidney volume (=0.4SD; p=0.041). After stratifying on gender, there seemed to be a somewhat stronger association in girls. Prenatal lead exposure may cause long-lasting effects on the kidney. This warrants follow-up studies in older children, as well as additional studies in other populations. Copyright © 2016. Published by Elsevier Inc.

  19. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells.

    PubMed

    Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  20. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

    PubMed Central

    Florencio-Silva, Rinaldo; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling. PMID:26247020

  1. Bisphosphonates and bone fractures in long-term kidney transplant recipients.

    PubMed

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

    2008-07-27

    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. 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. 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. 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.

  2. Anti-HLA antibodies and kidney allograft outcomes in recipients with donor bone marrow cell infusion.

    PubMed

    Solgi, Ghasem; Pourmand, Gholamreza; Mehrsai, Abdorasool; Taherimahmoudi, Mohsen; Nicknam, Mohmmad Hossein; Ebrahimi Rad, Mohmmad R; Seraji, Ali; Asadpoor, Amirabbas; Ansaripor, Bita; Nikbin, Behrouz; Amirzargar, Aliakbar

    2010-03-01

    Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concurrent donor bone marrow cell infusion (DBMI). Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre- and post-transplant (days 14, 30, and 90) sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA specific panel for antibody specification. Of 40 patients, 9 (22.5%) experienced acute rejection episodes (ARE) (6/20 cases in non-infused versus 3/20 in DBMI patients). The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones (88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively). A total of 10% (4/40) of patients developed donor specific anti-HLA antibodies (DSA) and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls. Our findings reveal an association between pre- and post-transplant anti-HLA antibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts.

  3. Current concepts and management strategies in chronic kidney disease-mineral and bone disorder.

    PubMed

    Chauhan, Veeraish; Kelepouris, Ellie; Chauhan, Nishtha; Vaid, Megha

    2012-09-01

    The term renal osteodystrophy describes the pathological changes in bone structure in chronic kidney disease (CKD); however, this term fails to describe adequately the adverse changes in mineral and hormonal metabolism in CKD that have grave consequences for patient survival. CKD-mineral and bone disorder (CKD-MBD) is a broader, newly defined term that should be used instead of renal osteodystrophy to define the mineral, bone, hormonal, and calcific cardiovascular abnormalities that are seen in CKD. The new paradigm in the management of renal bone disease is to "think beyond the bones" and strive to improve cardiovascular outcomes and survival. This means treating other aspects of the disease process that go beyond merely controlling parathyroid hormone levels. Primary physicians need to take a proactive approach to the management of CKD-MBD because the disorder begins early in the course of CKD, well before a patient is referred to a nephrologist. This review outlines the evidence behind the understanding of CKD-MBD, its implications for overall mortality, and the latest recommendations for management of CKD-MBD in patients with predialysis CKD.

  4. 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

  5. [Functional evaluation in patients with kidney calculi].

    PubMed

    Stojimirović, B

    1998-01-01

    Nephrolithiasis is a common disorder and a significant problem because of incidence, recurrence and severe consequences. Stone disease is a surgical as well as a medical problem. Major progress has been made recently in understanding the pathophysiological disturbances responsible for stone formation as well as in the techniques of stone removal. The introduction of extracorporeal shock wave lithotripsy has considerably reduced the need for surgery. Improvements in methods of kidney stone removal have not diminished the need for the application of an effective prophylactic program. The internist should take a complete history of stone events (number, composition, location and outcome of stone event), family history of stones, dietary habits (focusing on the consumption of animal protein, salt and dairy products), medications and physical examination. Radiopaque stones should be documented by plane X-ray films. Ultrasonography should be used to image calculi that are nonopaque, and to easily distinguish them from masses such as tumour or blood clot. Computed tomography is also an excellent method for imaging nonopaque renal calculi but higher cost and radiation exposure are disadvantages [2]. Crystallographic analysis is the essential diagnostic procedure. If available, previous stones should also be examined. "In stone disease, everything is measurement. What the laboratory cannot tell you, you will not know; what it tells you in error, you will not correct by using your instincts, your medical experience, or your art [3]". Reliable diagnostic protocols are available for the identification of different causes of stones. The complexity of protocols depend on the severity of nephrolithiasis. Patients with a single stone episode undergo simple protocol, and extensive detailed protocol is used for patients with recurrent stone disease, or patients at increased risk. Simple protocol, besides the already mentioned history of stone events, radiographic investigation and

  6. Low-level cadmium exposure and effects on kidney function.

    PubMed

    Wallin, Maria; Sallsten, Gerd; Lundh, Thomas; Barregard, Lars

    2014-12-01

    The nephrotoxicity of cadmium at low levels of exposure, measured by urinary cadmium, has recently been questioned since co-excretion of cadmium and proteins may have causes other than cadmium toxicity. The aim of this study was to explore the relation between kidney function and low or moderate cadmium levels, measured directly in kidney biopsies. We analysed cadmium in kidney biopsies (K-Cd), blood (B-Cd) and urine (U-Cd) from 109 living kidney donors in a cross-sectional study. We measured glomerular filtration rate (GFR), cystatin C in serum, albumin, β-2-microglobulin (B2M), retinol-binding protein (RBP), α-1-microglobulin (A1M), N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 (KIM-1) in 24 h and overnight urine. We found significant positive associations between A1M excretion and K-Cd in multiple regression models including age, sex, weight, smoking and urinary flow rate. This association was also present in never-smokers. A1M was also positively associated with B-Cd and U-Cd. GFR and the other biomarkers of kidney function were not associated with K-Cd. GFR estimated from serum cystatin C showed a very poor correlation with measured GFR. KIM-1, RBP and possibly albumin were positively associated with U-Cd, but only in overnight urine. No associations were found with B2M. Our results suggest that A1M in urine is a sensitive biomarker for effects of low-level cadmium exposure. A few associations between other renal biomarkers and U-Cd, but not K-Cd, were probably caused by physiological co-excretion or chance. 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.

  7. Low-level cadmium exposure and effects on kidney function

    PubMed Central

    Wallin, Maria; Sallsten, Gerd; Lundh, Thomas; Barregard, Lars

    2014-01-01

    Objectives The nephrotoxicity of cadmium at low levels of exposure, measured by urinary cadmium, has recently been questioned since co-excretion of cadmium and proteins may have causes other than cadmium toxicity. The aim of this study was to explore the relation between kidney function and low or moderate cadmium levels, measured directly in kidney biopsies. Methods We analysed cadmium in kidney biopsies (K-Cd), blood (B-Cd) and urine (U-Cd) from 109 living kidney donors in a cross-sectional study. We measured glomerular filtration rate (GFR), cystatin C in serum, albumin, β-2-microglobulin (B2M), retinol-binding protein (RBP), α-1-microglobulin (A1M), N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 (KIM-1) in 24 h and overnight urine. Results We found significant positive associations between A1M excretion and K-Cd in multiple regression models including age, sex, weight, smoking and urinary flow rate. This association was also present in never-smokers. A1M was also positively associated with B-Cd and U-Cd. GFR and the other biomarkers of kidney function were not associated with K-Cd. GFR estimated from serum cystatin C showed a very poor correlation with measured GFR. KIM-1, RBP and possibly albumin were positively associated with U-Cd, but only in overnight urine. No associations were found with B2M. Conclusions Our results suggest that A1M in urine is a sensitive biomarker for effects of low-level cadmium exposure. A few associations between other renal biomarkers and U-Cd, but not K-Cd, were probably caused by physiological co-excretion or chance. PMID:25286916

  8. Simple Cysts in Donor Kidney Contribute to Reduced Allograft Function.

    PubMed

    Qiu, Wenxian; Jiang, Yan; Wu, Jianyong; Huang, Hongfeng; Xie, Wenqing; Xie, Xishao; Chen, Jianghua; Peng, Wenhan

    2017-01-01

    Simple renal cysts may be an early marker of renal disease. We investigated whether simple cysts in donor kidney are associated with the decline of allograft function in living donor kidney transplantation. We retrospectively reviewed records of donors and recipients from 716 living donor kidney transplants performed between April 2007 and April 2015 in our hospital. Ninety-one donors with renal cysts and 64 recipients with cysts in donor kidney were noted. We compared these 64 cases to 128 no cyst-bearing controls matched for the donor gender, recipient gender, donor baseline serum creatinine (sCr), donor/recipient body surface area ratio, donor age, recipient age and the date of kidney transplantation in turn. The presence of cysts was interrelated with age, gender and renal function independently in donors. Pathological findings of time-zero biopsy revealed that donor kidney harboring cysts existed more glomerular sclerosis compared with no cyst-bearing controls (p = 0.040). The estimating glomerular filtration rate levels of recipients were 80.82 ± 26.61 vs. 88.21 ± 23.12, 66.95 ± 17.42 vs. 72.15 ± 16.42 and 60.92 ± 22.17 vs. 68.72 ± 14.43 ml/min· 1.73 m2 in cyst-bearing and no cyst-bearing group on day 7, month 6 and year 5, respectively, after surgery (p < 0.05). The mean sCr were 112.14 ± 48.32 vs. 98.75 ± 29.71 and 126.28 ± 42.32 vs. 115.05 ± 26.35 μmol/l on the 7th day and a half year after transplant, respectively (p < 0.05). The 2 groups did not significantly differ in terms of the other characteristics. Simple cysts in donor kidney can influence the early and long-term allograft function. In living donor transplantation, kidney presenting cysts should be considered carefully at the time of donor selection. © 2016 S. Karger AG, Basel.

  9. [Ovarian function in women after kidney transplantation].

    PubMed

    Pietrzak, B; Marianowski, L; Gradowska, L

    1994-08-01

    The full recovery of reproductive age patients suffering from chronic renal failure due to a successful transplant should include the restoration of normal reproductive functions. In the study data are presented concerning the resumption of menstruation and the evaluation of the ovarian function of renal transplant recipients. After a successful renal transplant the ovarian function improves considerably but isn't always fully restored which can be attributed to the renal efficiency grade or result from the administered immunosuppressive treatment. Approximately 40% of the patients have ovulatory cycles with a normal length of the luteal phase. 40% have also ovulatory cycles but the luteal phase is shorter and the progesterone values are lower. The remaining patients have anovulatory cycles with low estrogen values and a high FSH and LH concentration.

  10. The chronic kidney disease - Mineral bone disorder (CKD-MBD): Advances in pathophysiology.

    PubMed

    Hruska, Keith A; Sugatani, Toshifumi; Agapova, Olga; Fang, Yifu

    2017-01-21

    The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. New advances in the causes of the CKD-MBD are discussed in this review. They demonstrate that repair and disease processes in the kidneys release factors to the circulation that cause the systemic complications of CKD. The discovery of WNT inhibitors, especially Dickkopf 1 (Dkk1), produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical. This lead to the discovery that activin A is a second renal repair factor circulating in increased levels during CKD. Activin A derives from peritubular myofibroblasts of diseased kidneys, wherein it stimulates fibrosis, and decreases tubular klotho expression. Activin A binds to the type 2 activin A receptor, ActRIIA, which is variably affected by CKD in the vasculature. In diabetic/atherosclerotic aortas, specifically in vascular smooth muscle cells (VSMC), ActRIIA signaling is inhibited and contributes to CKD induced VSMC dedifferentiation, osteogenic transition and neointimal atherosclerotic calcification. In nondiabetic/nonatherosclerotic aortas, CKD increases VSMC ActRIIA signaling, and vascular fibroblast signaling causing the latter to undergo osteogenic transition and stimulate vascular calcification. In both vascular situations, a ligand trap for ActRIIA prevented vascular calcification. In the skeleton, activin A is responsible for CKD stimulation of osteoclastogenesis and bone remodeling increasing bone turnover. These studies demonstrate that circulating renal repair and injury factors are causal of the CKD-MBD and CKD associated cardiovascular disease.

  11. Evaluation of intense renal parenchymal activity (hot kidneys) on bone scintigraphy

    SciTech Connect

    Bernard, M.S.; Hayward, M.; Hayward, C.; Mundy, L. )

    1990-04-01

    The bone scintigrams of 600 patients performed over a 12-month period were reviewed. Thirty-six demonstrated abnormalities of the urinary tract of which six cases of intense renal parenchymal activity (hot kidneys) were found. Two cases were related to treatment with the new antineoplastic agent mitoxantrone. In one patient it was related to treatment with calcitonin. Neither of these associations has been previously reported. Recognized causes of hypercalcemia and recent radiotherapy were present in two patients. No cause could be found in the final patient.

  12. Interconnected Network Motifs Control Podocyte Morphology and Kidney Function

    PubMed Central

    Azeloglu, Evren U.; Hardy, Simon V.; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y.; Fang, Wei; Xiong, Huabao; Neves, Susana R.; Jain, Mohit R.; Li, Hong; Ma’ayan, Avi; Gordon, Ronald E.; He, John Cijiang; Iyengar, Ravi

    2014-01-01

    Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3′,5′-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element–binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor–driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease. PMID:24497609

  13. Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass.

    PubMed

    Galán, Isabel; Goicoechea, Marian; Quiroga, Borja; Macías, Nicolás; Santos, Alba; García de Vinuesa, Maria Soledad; Verdalles, Úrsula; Cedeño, Santiago; Verde, Eduardo; Pérez de José, Ana; García, Ana; Luño, José

    2017-08-30

    Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass. Retrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36-98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed. One hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall -1.6ml/min/1.73m(2)/year (-3.0, -0.7)). Male gender, albuminuria>100mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p=0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06-2.63), p=0.023; 1.02 (1.01-1.03), p=0.001 and HR: 2.14 (1.26-3.64), p=0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p=0.006). Hyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass. Copyright © 2017. Published by Elsevier España, S.L.U.

  14. The Relationship Between Pulmonary Emphysema and Kidney Function in Smokers

    PubMed Central

    Chandra, Divay; Stamm, Jason A.; Palevsky, Paul M.; Leader, Joseph K.; Fuhrman, Carl R.; Zhang, Yingze; Bon, Jessica; Duncan, Steven R.; Branch, Robert A.; Weissfeld, Joel; Gur, David; Gladwin, Mark T.

    2012-01-01

    Background: It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV1. Methods: Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans. Results: The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m2. Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m2 (P = .01), independent of airflow obstruction (FEV1), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV1 or quantitative CT scan measures of airway dimension. Conclusions: More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV1. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation. PMID:22459775

  15. The relationship between pulmonary emphysema and kidney function in smokers.

    PubMed

    Chandra, Divay; Stamm, Jason A; Palevsky, Paul M; Leader, Joseph K; Fuhrman, Carl R; Zhang, Yingze; Bon, Jessica; Duncan, Steven R; Branch, Robert A; Weissfeld, Joel; Gur, David; Gladwin, Mark T; Sciurba, Frank C

    2012-09-01

    It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV₁. Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans. The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m². Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m² (P = .01), independent of airflow obstruction (FEV₁), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV₁ or quantitative CT scan measures of airway dimension. More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV₁. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation.

  16. 188Re-labelled gemcitabine/bisphosphonate (Gem/BP): a multi-functional, bone-specific agent as a potential treatment for bone metastases.

    PubMed

    El-Mabhouh, Amal A; Mercer, John R

    2008-07-01

    This study investigated the bone-binding affinity and biodistribution of a (188)Re-labelled gemcitabine/bisphosphonate (Gem/BP) conjugate, a multi-functional drug designed to deliver tumour-specific combined radiotherapy and chemotherapy to the bone using the high bone-binding affinity of the bisphosphonate group. The Gem/BP conjugate was labelled at high radiochemical purity with (188)Re. The bone-binding affinity of the (188)Re-Gem/BP was studied in vitro in purified hydroxyapatite emulsion and powdered bovine bone. In vivo biodistribution studies were carried out in normal BALB/c mice. (188)Re-Gem/BP demonstrated strong and stable binding in both in vitro systems. In vivo (188)Re-Gem/BP showed bone uptake, rapid blood clearance and rapid elimination of unbound activity. The bone tissue demonstrated the highest concentration of bound radioactivity exempting the kidneys. Approximately 67% of retained whole-body activity was bound to the bone at 8 h after (188)Re-Gem/BP administration. (188)Re-Gem/BP demonstrated high, selective and persistent bone binding and can be considered as a model compound for multi-functional bone-specific therapy for bone metastases.

  17. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    PubMed

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  18. Renal Artery Stenting in Patients with a Solitary Functioning Kidney

    SciTech Connect

    Cioni, Roberto; Vignali, Claudio; Petruzzi, Pasquale; Neri, Emanuele; Caramella, Davide; Vagli, Paola; Bargellini, Irene; Napoli, Vinicio; Pinto, Stefania; Bartolozzi, Carlo

    2001-12-15

    Purpose: To retrospectively evaluate the results of renal artery stenting in patients with renovascular disease and a solitary functioning kidney.Methods: Palmazstents were placed in 16 patients with a solitary functioning kidney,renal artery stenosis, hypertension and renal failure. Stenoses were evaluated with color Doppler ultrasound, MR angiography and digital subtraction angiography (DSA). Indications for stenting were: recoil after percutaneous transluminal renal angioplasty (PTRA) (63%),arterial dissection after PTRA (13%) and primary stenting (25%).Immediate results were evaluated by DSA. On follow-up (6-36 months),patients underwent periodical evaluation of clinical conditions (blood pressure and serum creatinine level) and stent patency, by means of color Doppler ultrasound.Results: Stent placement was successful in all patients (100%). Cumulative primary patency rate was: 100% at 1 day, 93.75% at 6 months, 81.25% at 12 months and 75% at 24 months. A significant reduction in diastolic blood pressure occurred (mean {+-} SD 104 {+-} 6 vs 92 {+-} 3;p < 0.05); renal function improved or stabilized in over 80% of patients. However, there was no significant difference in the creatinine values before and after treatment (mean {+-} SD 200 {+-} 142 mmol/l vs 197 {+-} 182 mmol/l; p> 0.05).Conclusion: Renal artery stenting, both after PTRA and as primary stenting, represents a safe procedure, able to preserve renal function in patients with a solitary functioning kidney.

  19. Curcumin Ameliorates Kidney Function and Oxidative Stress in Experimental Chronic Kidney Disease.

    PubMed

    Ali, Badreldin H; Al-Salam, Suhail; Al Suleimani, Yousuf; Al Kalbani, Jamila; Al Bahlani, Shadia; Ashique, Mohammed; Manoj, Priyadarsini; Al Dhahli, Buthaina; Al Abri, Nadia; Naser, Heba T; Yasin, Javed; Nemmar, Abderrahim; Al Za'abi, Mohammed; Hartmann, Christina; Schupp, Nicole

    2017-05-31

    Chronic kidney disease (CKD) is known to involve inflammation, oxidative stress and apoptosis. Here, we investigated the impact of curcumin (diferuloyl methane, a phenolic turmeric pigment), which has strong antioxidant, anti-inflammatory and anti-apoptotic activities on kidney structure and function in rats with adenine-induced CKD. Rats were treated for 5 weeks with adenine to induce CKD-like renal damage and combined with three doses of curcumin. Markers of kidney function and oxidative stress were quantified in plasma, urine, renal homogenates and on kidney tissue. Curcumin was found to significantly abate adenine-induced toxic effects such as reduced creatinine clearance, elevated neutrophil gelatinase-associated lipocalin levels and raised urinary N-acetyl-β-D-glucosaminidase activities. Curcumin markedly reduced renal morphological damage and histopathological markers of inflammation, fibrosis and apoptosis. Curcumin further reduced adenine-induced hypertension, urinary albumin, the inflammatory cytokines IL-1β, IL-6 and TNF-α, cystatin C and adiponectin. It restored plasma sclerostin concentrations and lowered oxidative stress in renal homogenates. In animals treated with the two higher curcumin concentrations, alone or in combination with adenine, an increased expression of the antioxidative transcription factor Nrf2 was found as well as up-regulation of the activity of its direct target glutathione reductase, and of an indirect target, the glutathione level. In conclusion, curcumin exhibits salutary effects against adenine-induced CKD in rats by reducing inflammation and oxidative stress via up-regulation of the transcription factor Nrf2. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  20. FGF23 neutralization improves bone quality and osseointegration of titanium implants in chronic kidney disease mice

    PubMed Central

    Sun, Ningyuan; Guo, Yuchen; Liu, Weiqing; Densmore, Michael; Shalhoub, Victoria; Erben, Reinhold G.; Ye, Ling; Lanske, Beate; Yuan, Quan

    2015-01-01

    Chronic kidney disease (CKD) is a worldwide health problem. Serum levels of FGF23, a phosphaturic hormone, increase at the earliest stages of CKD, and have been found to be independently associated with the mortality and morbidity of CKD patients. The purpose of this study was to evaluate whether FGF23 neutralization was able to improve bone quality and osseointegration of titanium implants. Uremia was induced by 5/6 nephrectomy in adult female mice. Postsurgery, the mice were injected with vehicle or FGF23 neutralizing antibody (5 mg/kg body weight) 3 times a week. Experimental titanium implants were inserted in the distal end of the femurs. FGF23 neutralization significantly increased serum phosphate, 1,25(OH)2D and BUN, and decreased serum PTH and FGF23, relative to vehicle-treated CKD mice. Histomorphometric analysis of the tibiae indicated that FGF23 neutralization normalized the osteoidosis observed in vehicle-treated CKD mice. Although bone-implant contact ratio remained unchanged by anti-FGF23 antibody treatment, the strength of osseointegration, as evidenced by a biomechanical push-in test, was significantly improved by FGF23 neutralization. Our findings revealed that FGF23 neutralization effectively improves bone quality and osseointegration of titanium implants in CKD mice, suggesting FGF23 as a key factor of CKD related bone diseases. PMID:25665715

  1. The consequences of chronic kidney disease on bone metabolism and growth in children

    PubMed Central

    Bacchetta, Justine; Harambat, Jérôme; Cochat, Pierre; Salusky, Isidro B.; Wesseling-Perry, Katherine

    2012-01-01

    Growth retardation, decreased final height and renal osteodystrophy (ROD) are common complications of childhood chronic kidney disease (CKD), resulting from a combination of abnormalities in the growth hormone (GH) axis, vitamin D deficiency, hyperparathyroidism, hypogonadism, inadequate nutrition, cachexia and drug toxicity. The impact of CKD-associated bone and mineral disorders (CKD–MBD) may be immediate (serum phosphate/calcium disequilibrium) or delayed (poor growth, ROD, fractures, vascular calcifications, increased morbidity and mortality). In 2012, the clinical management of CKD–MBD in children needs to focus on three main objectives: (i) to provide an optimal growth in order to maximize the final height with an early management with recombinant GH therapy when required, (ii) to equilibrate calcium/phosphate metabolism so as to obtain acceptable bone quality and cardiovascular status and (iii) to correct all metabolic and clinical abnormalities that can worsen bone disease, growth and cardiovascular disease, i.e. metabolic acidosis, anaemia, malnutrition and 25(OH)vitamin D deficiency. The aim of this review is to provide an overview of the mineral, bone and vascular abnormalities associated with CKD in children in terms of pathophysiology, diagnosis and clinical management. PMID:22851629

  2. FGF23 neutralization improves bone quality and osseointegration of titanium implants in chronic kidney disease mice.

    PubMed

    Sun, Ningyuan; Guo, Yuchen; Liu, Weiqing; Densmore, Michael; Shalhoub, Victoria; Erben, Reinhold G; Ye, Ling; Lanske, Beate; Yuan, Quan

    2015-02-10

    Chronic kidney disease (CKD) is a worldwide health problem. Serum levels of FGF23, a phosphaturic hormone, increase at the earliest stages of CKD, and have been found to be independently associated with the mortality and morbidity of CKD patients. The purpose of this study was to evaluate whether FGF23 neutralization was able to improve bone quality and osseointegration of titanium implants. Uremia was induced by 5/6 nephrectomy in adult female mice. Postsurgery, the mice were injected with vehicle or FGF23 neutralizing antibody (5 mg/kg body weight) 3 times a week. Experimental titanium implants were inserted in the distal end of the femurs. FGF23 neutralization significantly increased serum phosphate, 1,25(OH)2D and BUN, and decreased serum PTH and FGF23, relative to vehicle-treated CKD mice. Histomorphometric analysis of the tibiae indicated that FGF23 neutralization normalized the osteoidosis observed in vehicle-treated CKD mice. Although bone-implant contact ratio remained unchanged by anti-FGF23 antibody treatment, the strength of osseointegration, as evidenced by a biomechanical push-in test, was significantly improved by FGF23 neutralization. Our findings revealed that FGF23 neutralization effectively improves bone quality and osseointegration of titanium implants in CKD mice, suggesting FGF23 as a key factor of CKD related bone diseases.

  3. Advances in noninvasive functional imaging of bone.

    PubMed

    Lan, Sheng-Min; Wu, Ya-Na; Wu, Ping-Ching; Sun, Chi-Kuang; Shieh, Dar-Bin; Lin, Ruey-Mo

    2014-02-01

    The demand for functional imaging in clinical medicine is comprehensive. Although the gold standard for the functional imaging of human bones in clinical settings is still radionuclide-based imaging modalities, nonionizing noninvasive imaging technology in small animals has greatly advanced in recent decades, especially the diffuse optical imaging to which Britton Chance made tremendous contributions. The evolution of imaging probes, instruments, and computation has facilitated exploration in the complicated biomedical research field by allowing longitudinal observation of molecular events in live cells and animals. These research-imaging tools are being used for clinical applications in various specialties, such as oncology, neuroscience, and dermatology. The Bone, a deeply located mineralized tissue, presents a challenge for noninvasive functional imaging in humans. Using nanoparticles (NP) with multiple favorable properties as bioimaging probes has provided orthopedics an opportunity to benefit from these noninvasive bone-imaging techniques. This review highlights the historical evolution of radionuclide-based imaging, computed tomography, positron emission tomography, and magnetic resonance imaging, diffuse optics-enabled in vivo technologies, vibrational spectroscopic imaging, and a greater potential for using NPs for biomedical imaging.

  4. Better recovery of kidney function in patients with de novo chronic kidney disease after partial nephrectomy compared with those with pre-existing chronic kidney disease.

    PubMed

    Takagi, Toshio; Kondo, Tsunenori; Iizuka, Junpei; Omae, Kenji; Kobayashi, Hirohito; Hashimoto, Yasunobu; Yoshida, Kazuhiko; Tanabe, Kazunari

    2014-06-01

    We compared kidney functional recovery between patients with pre-existing chronic kidney disease, those with de novo chronic kidney disease and those with normal kidney function, after partial nephrectomy. A total of 311 patients who underwent partial nephrectomy at Tokyo Women's Medical University Hospital, Tokyo, Japan, between January 2004 and July 2011 with sufficient kidney functional data participated in the study. Patients with pre-existing chronic kidney disease (group1: 78 patients) were defined as those with estimated glomerular filtration rate under 60 mL/min/m(2) before partial nephrectomy. Patients with de novo chronic kidney disease (group 2: 49) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) before surgery and who developed estimated glomerular filtration rate under 60 mL/min/m(2) 3 months after partial nephrectomy. Normal patients (group 3: 184) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) both before and after partial nephrectomy. Group 1 was associated with older age and higher comorbidity, including hypertension and diabetes mellitus, compared with other groups. R.E.N.A.L. score was not significantly different between the groups. Although the percent change of estimated glomerular filtration rate between the preoperative period and 3 months after partial nephrectomy in group 2 was significantly decreased compared with that in other groups (group 1: -6.8%, group 2: -18%, group 3: -7.3%), the renal functional recovery between 3 and 12 months after partial nephrectomy in group 2 was better than that in other groups (group 1: -0.5%, group 2: 5.6%, group 3: -0.4%). Patients with de novo chronic kidney disease had better kidney functional recovery than the other two groups, which might suggest that they were surgically assaulted and developed chronic kidney disease in the early postoperative period, and were essentially different from those with pre-existing chronic kidney

  5. Investigation of the relationship between low environmental exposure to metals and bone mineral density, bone resorption and renal function.

    PubMed

    Callan, A C; Devine, A; Qi, L; Ng, J C; Hinwood, A L

    2015-07-01

    Environmental exposure to metals has been linked to adverse health outcomes. Exposure to cadmium has been associated with decreased bone density, an increased risk of osteoporotic fracture and possible renal dysfunction. Older women are a group at risk of renal and bone density impacts and exposure to metals may be an important risk factor for these health outcomes. This study was a cross sectional study of 77 women aged 50 years and above examining the relationship between metals exposure and renal and bone health. Urinary and blood metals concentrations, plasma creatinine, iron, ferritin and transferrin were measured in these subjects. Bone biomarkers assessed included the pyridinium crosslinks, pyridinoline and deoxypyridinoline measured by ELISA. Renal function was assessed using eGFR and KIM-1. Whole body, hip and lumbar spine bone mineral density was assessed using DEXA. Blood and urinary metals concentrations were generally low in the subjects, with a median urinary cadmium concentration of 0.26 μg/g creatinine (range <0.065-1.03 μg/g). Urinary cadmium was found to be a significant predictor of bone mineral density at whole body, lumber spine, total hip and femoral neck, with increasing urinary Cd concentrations associated with decreased bone density. Urinary cadmium and aluminium concentrations were positively correlated with bone resorption whilst blood zinc and mercury concentrations were negatively correlated. Urinary aluminium was positively correlated with KIM-1 concentrations, a marker of early kidney damage, however blood zinc concentrations were significantly negatively correlated with this biomarker. This study provides additional support for low cadmium exposure being of concern for the health of older women. Further investigation into the role of exposure to other metals on bone and renal health is warranted.

  6. Association of Kidney Function and Early Kidney Injury With Incident Hypertension in HIV-Infected Women.

    PubMed

    Ascher, Simon B; Scherzer, Rebecca; Peralta, Carmen A; Tien, Phyllis C; Grunfeld, Carl; Estrella, Michelle M; Abraham, Alison; Gustafson, Deborah R; Nowicki, Marek; Sharma, Anjali; Cohen, Mardge H; Butch, Anthony W; Young, Mary A; Bennett, Michael R; Shlipak, Michael G

    2017-02-01

    Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected people. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C, urine albumin-to-creatinine ratio, and 7 urine biomarkers of tubular injury: α-1-microglobulin, interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, N-acetyl-β-d-glucosaminidase, and α1-acid-glycoprotein. We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as 2 consecutive visits of antihypertensive medication use. During a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher urine albumin-to-creatinine ratio was independently associated with incident hypertension (relative risk =1.13 per urine albumin-to-creatinine ratio doubling, 95% confidence interval, 1.07-1.20), as was lower estimated glomerular filtration rate (relative risk =1.10 per 10 mL/min/1.73 m(2) lower estimated glomerular filtration rate; 95% confidence interval, 1.04-1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, urine albumin-to-creatinine ratio was not associated with incident hypertension, whereas higher urine interleukin-18, α1-acid-glycoprotein, and N-acetyl-β-d-glucosaminidase levels were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in

  7. Functional assessment of transplanted kidneys with magnetic resonance imaging.

    PubMed

    Wang, Yu-Ting; Li, Ying-Chun; Yin, Long-Lin; Pu, Hong; Chen, Jia-Yuan

    2015-10-28

    Kidney transplantation has emerged as the treatment of choice for many patients with end-stage renal disease, which is a significant cause of morbidity and mortality. Given the shortage of clinically available donor kidneys and the significant incidence of allograft dysfunction, a noninvasive and accurate assessment of the allograft renal function is critical for postoperative management. Prompt diagnosis of graft dysfunction facilitates clinical intervention of kidneys with salvageable function. New advances in magnetic resonance imaging (MRI) technology have enabled the calculation of various renal parameters that were previously not feasible to measure noninvasively. Diffusion-weighted imaging provides information on renal diffusion and perfusion simultaneously, with quantification by the apparent diffusion coefficient, the decrease of which reflects renal function impairment. Diffusion-tensor imaging accounts for the directionality of molecular motion and measures fractional anisotropy of the kidneys. Blood oxygen level-dependent MR evaluates intrarenal oxygen bioavailability, generating the parameter of R2* (reflecting the concentration of deoxyhemoglobin). A decrease in R2* could happen during acute rejection. MR nephro-urography/renography demonstrates structural data depicting urinary tract obstructions and functional data regarding the glomerular filtration and blood flow. MR angiography details the transplant vasculature and is particularly suitable for detecting vascular complications, with good correlation with digital subtraction angiography. Other functional MRI technologies, such as arterial spin labeling and MR spectroscopy, are showing additional promise. This review highlights MRI as a comprehensive modality to diagnose a variety of etiologies of graft dysfunction, including prerenal (e.g., renal vasculature), renal (intrinsic causes) and postrenal (e.g., obstruction of the collecting system) etiologies.

  8. Functional status and survival after kidney transplantation1–12

    PubMed Central

    Reese, Peter P.; Bloom, Roy D.; Shults, Justine; Thomasson, Arwin; Mussell, Adam; Rosas, Sylvia E.; Johansen, Kirsten L.; Abt, Peter; Levine, Matthew; Caplan, Arthur; Feldman, Harold I.; Karlawish, Jason

    2013-01-01

    Background Older patients constitute a growing proportion of U.S. kidney transplant recipients and often have a high burden of comorbidities. A summary measure of health such as functional status might enable transplant professionals to better evaluate and counsel these patients about their prognosis after transplant. Methods We linked UNOS registry data about post-transplant survival with pre-transplant functional status data (physical function [PF] scale of the Medical Outcomes Study Short Form-36) among individuals undergoing kidney transplant from 6/1/2000 – 5/31/2006. We examined the relationship between survival and functional status with multivariable Cox regression, adjusted for age. Using logistic regression models for three-year survival, we also estimated the reduction in deaths in the hypothetical scenario that recipients with poor functional status in this cohort experienced modest improvements in function. Results The cohort comprised 10,875 kidney transplant recipients (KTRs) with a mean age of 50 years; 14% were ≥65. Differences in three-year mortality between highest and lowest PF groups ranged from 3% among recipients <35 years to 14% among recipients ≥65 years. In multivariable Cox regression, worse PF was associated with higher mortality (HR 1.66 for lowest versus highest PF quartiles; p<0.001). Interactions between PF and age were non-significant. We estimated that 11% fewer deaths would occur if KTRs with the lowest functional status experienced modest improvements in function. Conclusions Across a wide age range, functional status was an independent predictor of post-transplant survival. Functional status assessment may be a useful tool with which to counsel patients about post-transplant outcomes. PMID:24113514

  9. Cystatin C and renal function in pediatric kidney transplant recipients.

    PubMed

    Franco, M C P; Nagasako, S S; Machado, P G; Nogueira, P C K; Pestana, J O M; Sesso, R

    2009-12-01

    In clinical practice, the glomerular filtration rate (GFR) is often determined with serum creatinine. However, studies have shown cystatin C to be a better parameter for the diagnosis of impaired renal function. We compared GFR estimated by plasma cystatin C with GFR estimated by serum creatinine in a sample of 50 pediatric renal transplant recipients and 24 healthy children. The correlation between GFR estimated by serum creatinine and by cystatin C was significant (r = 0.75; P < 0.001, Person's correlation); however, in pediatric kidney transplant recipients, the GFR was 6.7 mL/min lower when determined using cystatin C rather than serum creatinine. Moreover, using GFR estimated by cystatin C we found that 42% of the pediatric kidney transplant recipients had an estimated GFR <60 mL.min-1.1.73 (m(2))-1, whereas when GFR was estimated by the serum creatinine formula only 16% of the children had values below this cutoff point indicative of chronic kidney disease (P < 0.001). We conclude that, in pediatric kidney transplant recipients, estimation of GFR yields lower values when cystatin C is used rather than serum creatinine.

  10. [Kidney and bone update : the 5-year history and future of CKD-MBD. Disorders of musculoskeletal system in CKD ; bone fracture and periarticular calcification].

    PubMed

    Yamada, Shunsuke; Taniguchi, Masatomo

    2012-07-01

    Chronic kidney disease-mineral and bone disorder (CKD-MBD) affects life expectancy through vascular calcification, and impairs patient's activity of daily living (ADL) and quality of life (QOL) through bone fracture and periarticular calcification. In CKD patients, vitamin D deficiency and secondary hyperparathyroidism impairs bone strength, and muscle dysfunction related to vitamin D deficiency also causes easy fall, leading to the high risk of bone fracture. Bone fracture not only aggravates ADL and QOL but increases the risk of mortality. Periarticular calcification such as tumoral calcinosis in relation to CKD-MBD causes restricted range of articular motion, leading to the deterioration of patient's ADL and QOL. Because bone fragility and tumoral calcinosis occurs in relation to CKD-MBD, the appropriate management of CKD-MBD is madatory.

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

    PubMed Central

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

    2016-01-01

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

  12. Reduced kidney function is a risk factor for atrial fibrillation.

    PubMed

    Laukkanen, Jari A; Zaccardi, Francesco; Karppi, Jouni; Ronkainen, Kimmo; Kurl, Sudhir

    2016-08-01

    There is limited knowledge on the relationship between kidney function and incidence of atrial fibrillation. Thus, this prospective study was designed to evaluate whether various biomarkers of kidney function are associated to the risk of atrial fibrillation. The study population consisted of 1840 subjects (615 women and 1225 men) aged 61-82 years. Cystatin C- and creatinine-based estimation of glomerular filtration rate (eGFRcys and eGRFcreat , respectively) and urinary albumin/creatinine ratio (ACR) were assessed to investigate their relationship with the risk of atrial fibrillation. During a median follow-up of 3.7 years, a total of 159 incident atrial fibrillation cases occurred. After adjustment for potential confounders, the risk of atrial fibrillation was increased (hazard ratio 2.74, 95% confidence interval (CI) 1.56-4.81, P < 0.001) in subjects with reduced kidney function (eGFRcys , 15-59 mL/min per 1.73 m(2) ) compared to subjects with normal kidney function (≥90 mL/min per 1.73 m(2) ). Similar results were also found when comparing the respective groups of subjects defined by their eGRFcreat levels (hazard ratio 2.41, CI 1.09-5.30, P = 0.029). Consistently, subjects with ACR ≥300 mg/g had an increased risk of incident atrial fibrillation (hazard ratio 2.16, CI 1.35-2.82, P < 0.001) compared to those with ACR <30 mg/g. Reduced eGFR and albuminuria were associated with an increased risk of atrial fibrillation.

  13. Kidney function outcomes following thermal ablation of small renal masses

    PubMed Central

    Raman, Jay D; Jafri, Syed M; Qi, David

    2016-01-01

    The diagnosis of small renal masses (SRMs) continues to increase likely attributable to widespread use of axial cross-sectional imaging. Many of these SRMs present in elderly patients with abnormal baseline renal function. Such patients are at risk for further decline following therapeutic intervention. Renal thermal ablation presents one approach for management of SRMs whereby tumors are treated in situ without need for global renal ischemia. These treatment characteristics contribute to favorable renal function outcomes following kidney tumor ablation particularly in patients with an anatomic or functional solitary renal unit. PMID:27152264

  14. Effects of Uremic Toxins from the Gut Microbiota on Bone: A Brief Look at Chronic Kidney Disease.

    PubMed

    Black, Ana Paula; Cardozo, Ludmila F M F; Mafra, Denise

    2015-10-01

    Patients with chronic kidney disease (CKD) frequently have mineral and bone disorders (CKD-MBD) that are caused by several mechanisms. Recent research has suggested that uremic toxins from the gut such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) could also be involved in the development of bone disease in patients with CKD. IS and PCS are produced by microbiota in the gut, carried into the plasma bound to serum albumin, and are normally excreted into the urine. However, in patients with CKD, there is an accumulation of high levels of these uremic toxins. The exact mechanisms of action of uremic toxins in bone disease remain unclear. The purpose of this brief review is to discuss the link between uremic toxins (IS and PCS) and bone mineral disease in chronic kidney disease. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  15. Relation between body mass index and bone mineral density among haemodialysis patients with chronic kidney disease.

    PubMed

    Castillo, Rafael Fernández; de la Rosa, Rafael José Esteban

    2009-03-01

    Renal osteodystrophy is a serious problem for patients with chronic kidney disease. Measurements of bone mineral density, T-score and Z-score were taken in the lumbar region and femur of 73 patients who were being treated on the haemodialysis programme. These measurements were compared with the anthropometric values of weight, height and body mass index (BMI) obtaining a positive correlation between them. Alterations in the bone mineral metabolism are an important cause of morbidity and mortality among haemodialysis patients with chronic renal failure. Bone mass diminution, together with fracture risk, is a frequent finding in these patients; this fact is explained by different factors, amongst which are those related to their anthropometric values. Bone mineral density (BMD) was studied, T-score and Z-score measurements were taken in the neck of the femur, trochanter, intertrochanter, 1/3 of proximal femur, Ward's triangle and L2, L3 and L4 vertebrae; body composition was also studied. With this aim, DXA densitometry was used on 73 haemodialysis patients (40 men and 33 women). The mean of the total haemodialysis time in these patients was 9.7 years. The group showed a very significant positive correlation between BMD, weight, height, BMI, fractures, dialysis time and intact PTH. CKD patients undergoing the haemodialysis programme show a significant BMD reduction, which affects both lumbar spine and femur. Weight and height affect BMD and bone change, being thus important factors of prediction for fracture risk. Furthermore, BMI is the main determinant of BMD, a finding that is confirmed in the units in this study and with the evidence described by other authors (Negri et al. (2005).

  16. Dietary Fiber, Kidney Function, Inflammation, and Mortality Risk

    PubMed Central

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M.; Cederholm, Tommy; Ärnlöv, Johan; Lindholm, Bengt; Sjögren, Per

    2014-01-01

    Background and objectives In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Design, setting, participants, & measurements Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70–71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991–1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Results Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m2 per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m2) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m2 (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). Conclusions High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also

  17. Dietary fiber, kidney function, inflammation, and mortality risk.

    PubMed

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M; Cederholm, Tommy; Arnlöv, Johan; Lindholm, Bengt; Sjögren, Per; Carrero, Juan Jesús

    2014-12-05

    In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70-71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991-1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m(2) per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m(2)) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m(2) (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney

  18. Changes in kidney function among Nicaraguan sugarcane workers

    PubMed Central

    Laws, Rebecca L; Brooks, Daniel R; Amador, Juan José; Weiner, Daniel E; Kaufman, James S; Ramírez-Rubio, Oriana; Riefkohl, Alejandro; Scammell, Madeleine K; López-Pilarte, Damaris; Sánchez, José Marcel; Parikh, Chirag R; McClean, Michael D

    2015-01-01

    Background: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers. Objectives: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria. Methods: We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR). Results: eGFR varied by job and decreased during the harvest in seed cutters (−8.6 ml/min/1.73 m2), irrigators (−7.4 ml/min/1.73 m2), and cane cutters (−5.0 ml/min/1.73 m2), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g. Conclusions: The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are occupational. PMID:25631575

  19. Ultrasonic imaging characteristics of transplanted kidneys with delayed graft function.

    PubMed

    Liang, W X; Cai, M J; Jiang, L; Xie, Y Q; Yuan, W L; Zhang, H

    2014-08-29

    We investigated the ultrasonic imaging characteristics of transplanted kidneys with delayed graft function (DGF). Ultrasonography was performed in 44 patients after kidney transplantation, and a time-intensity analysis was performed to compare the differences between patients with normal graft function (NGF) and those with DGF. Compared with the NGF group, the DGF group had earlier arrival time, shorter time to peak, and higher arrival intensity and peak intensity (P < 0.05). The variation-of-intensity parameters in different renal cortices increased, whereas the variation-of-time parameter decreased, in those with DGF (P < 0.05). In conclusion, compared with the NGF group, the microcirculation perfusion of transplanted kidneys in the DGF group showed higher perfusion with earlier arrival time, shorter time to peak, and higher arrival intensity and peak intensity. In addition, the intensity variations of contrast agent in different renal cortices from patients with DGF were greater, whereas the variations in perfusion time were smaller than those in patients with NGF.

  20. The Role of Vitamin D in the FGF23, Klotho, and Phosphate Bone-Kidney Endocrine Axis

    PubMed Central

    Haussler, Mark R.; Whitfield, G. Kerr; Kaneko, Ichiro; Forster, Ryan; Saini, Rimpi; Hsieh, Jui-Cheng; Haussler, Carol A.; Jurutka, Peter W.

    2011-01-01

    1,25-dihydroxyvitamin D (1,25D), through association with the nuclear vitamin D receptor (VDR), exerts control over a novel endocrine axis consisting of the bone-derived hormone FGF23, and the kidney-expressed klotho, CYP27B1, and CYP24A1 genes, which together prevent hyperphosphatemia/ectopic calcification and govern the levels of 1,25D to maintain bone mineral integrity while promoting optimal function of other vital tissues. When occupied by 1,25D, VDR interacts with RXR to form a heterodimer that binds to VDREs in the region of genes directly controlled by 1,25D (e.g., FGF23, klotho, Npt2c, CYP27B1 and CYP24A1). By recruiting complexes of comodulators, activated VDR initiates a series of events that induces or represses the transcription of genes encoding proteins such as: the osteocyte-derived hormone, FGF23; the renal anti-senescence factor and protein co-receptor for FGF23, klotho; other mediators of phosphate transport including Npt2a/c; and vitamin D hormone metabolic enzymes, CYP27B1 and CYP24A1. The mechanism whereby osteocytes are triggered to release FGF23 is yet to be fully defined, but 1,25D, phosphate, and leptin appear to play major roles. The kidney responds to FGF23 to elicit CYP24A1-catalyzed detoxification of the 1,25D hormone while also repressing both Npt2a/c to mediate phosphate elimination and CYP27B1 to limit de novo 1,25D synthesis. Comprehension of these skeletal and renal actions of 1,25D should facilitate the development of novel mimetics to prevent ectopic calcification, chronic renal and vascular disease, and promote healthful aging. PMID:21932165

  1. Bone tissue remodeling and development: focus on matrix metalloproteinase functions.

    PubMed

    Paiva, Katiucia Batista Silva; Granjeiro, José Mauro

    2014-11-01

    Bone-forming cells originate from distinct embryological layers, mesoderm (axial and appendicular bones) and ectoderm (precursor of neural crest cells, which mainly form facial bones). These cells will develop bones by two principal mechanisms: intramembranous and endochondral ossification. In both cases, condensation of multipotent mesenchymal cells occurs, at the site of the future bone, which differentiate into bone and cartilage-forming cells. During long bone development, an initial cartilaginous template is formed and replaced by bone in a coordinated and refined program involving chondrocyte proliferation and maturation, vascular invasion, recruitment of adult stem cells and intense remodeling of cartilage and bone matrix. Matrix metalloproteinases (MMPs) are the most important enzymes for cleaving structural components of the extracellular matrix (ECM), as well as other non-ECM molecules in the ECM space, pericellular perimeter and intracellularly. Thus, the bioactive molecules generated act on several biological events, such as development, tissue remodeling and homeostasis. Since the discovery of collagenase in bone cells, more than half of the MMP members have been detected in bone tissues under both physiological and pathological conditions. Pivotal functions of MMPs during development and bone regeneration have been revealed by knockout mouse models, such as chondrocyte proliferation and differentiation, osteoclast recruitment and function, bone modeling, coupling of bone resorption and formation (bone remodeling), osteoblast recruitment and survival, angiogenesis, osteocyte viability and function (biomechanical properties); as such alterations in MMP function may alter bone quality. In this review, we look at the principal properties of MMPs and their inhibitors (TIMPs and RECK), provide an up-date on their known functions in bone development and remodeling and discuss their potential application to Bone Bioengineering. Copyright © 2014 Elsevier Inc

  2. History of fluid balance and kidney function in space.

    PubMed

    Drummer, Christian; Cirillo, Massimo; De Santo, Natale G

    2004-01-01

    During the last four decades, about 400 people have been in Space, since Yuri Gagarin was sent in 1961 as the first human into Earth orbit. From the very beginning, the circulatory system of astronauts (meaning heart, vascular system, body fluid distribution and balance, and the kidney) was central to the medical concerns of Space physiologists and physicians because of its gravity-dependence. The present manuscript puts emphasize on some key scientists who worked in the field of body fluid regulation and kidney function in the USA, in Russia and in Europe during recent decades. The manuscript in particular summarizes the outcome of this research and describes the present understanding of how the body fluid regulatory system adapts to the extreme environment of Space.

  3. [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Lanthanum carbonate and new phosphate binders in patients with chronic kidney disease].

    PubMed

    Negi, Shigeo; Shigematsu, Takashi

    2010-07-01

    Hyperphosphatemia is a serious complication which has been linked with an increased risk of cardiovascular mortality in patients with chronic kidney disease. Lanthanum carbonate is a novel non-calcium, non-aluminum phosphate-binding agent, and has approved for clinical use in patients on hemodialysis in Japan on March in 2009. Compared to calcium carbonate and sevelamer hydrochloride, lanthanum carbonate is a powerful phosphate binder. There is no evidence of bone toxicity and neurotoxicity of lanthanum carbonate previously reported for aluminium hydroxide. However, further studies are needed to address the longer term toxic effect on bone and other organs.

  4. Kidney Function and Disability-Free Survival in Older Women.

    PubMed

    Cavanaugh, Alyson M; LaCroix, Andrea Z; Kritz-Silverstein, Donna; Rillamas-Sun, Eileen; Rifkin, Dena E

    2017-01-01

    To examine the prospective association between kidney function and three outcomes: survival to age 85 with functional independence, survival to age 85 with disability, and death before age 85. Prospective study. Women's Health Initiative, conducted at 40 U.S. clinical centers. Postmenopausal women enrolled between 1993 and 1998 with baseline biomarker assessments who had the potential to reach age 85 before September 2013 (N = 7,178). Kidney function was measured according to estimated glomerular filtration rate (eGFR) calculated from serum creatinine collected at baseline. Outcomes were survival to age 85 with functional independence, survival with disability, or death before age 85. Disability was defined as mobility or activity of daily living limitations measured by questionnaire. eGFR was greater than 90 mL/min per 1.73 m(2) in 22.7% of women, 60 to 89 mL/min per 1.73 m(2) in 66.5%, 45 to 59 mL/min per 1.73 m(2) in 8.7%, and less than 45 mL/min per 1.73 m(2) in 2.0%. Median follow-up was 15 years. Of 4,953 survivors, 3,155 reported no physical disability at age 85. Two thousand two hundred twenty-five participants died before age 85. Women with an eGFR of 90 mL/min per 1.73 m(2) or greater had 2.71 times greater odds of survival to age 85 with functional independence than of dying before 85 (95% confidence interval (CI) = 1.62-4.51) than those with an eGFR less than 45 mL/min per 1.73 m(2) , women with an eGFR of 60 to 89 mL/min per 1.73 m(2) had 3.04 times (95% CI = 1.85-5.00) greater odds, and women with an eGFR of 45 to 59 mL/min per 1.73 m(2) had 2.22 times (95% CI = 1.31-3.76) greater odds. Similar, but slightly weaker odds were seen for survival to age 85 with disability. Better kidney function was not significantly associated with greater likelihood of survival to age 85 with independent function than of surviving with disability. Better kidney function was associated with greater likelihood of survival to age 85 with and without disability. © 2016

  5. The binding of the bone morphogenetic protein antagonist gremlin to kidney heparan sulfate: Such binding is not essential for BMP antagonism.

    PubMed

    Tatsinkam, Arnold Junior; Rune, Naomi; Smith, Joy; Norman, Jill T; Mulloy, Barbara; Rider, Christopher C

    2017-02-01

    Gremlin-1, a bone morphogenetic protein (BMP) antagonist, has essential roles in kidney and limb bone development, and is important in chronic diseases including tissue fibrosis. It also functions as an activating ligand of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), and binds strongly to the sulfated polysaccharide, heparin. Here we investigated the extent to which gremlin binds to the related polysaccharide heparan sulfate (HS), which unlike heparin is widely distributed spread within tissues. We determined that both highly sulfated HS and kidney HS are able to partially compete for the binding of heparin to gremlin, whereas low sulfated HS is a poor competitor. In further investigations of the interaction between gremlin and HS, we found that wild-type gremlin is able to bind broadly across the various regions of kidney in an HS-dependent manner, with particularly intense binding to tubular structures in the renal cortex. In a model of chronic kidney disease, fibrotic changes in the kidney result in a loss of gremlin binding sites. Gremlin mutants with reduced affinity for heparin showed negligible binding under the same conditions. These mutants nonetheless remain functional as BMP antagonists on C2C12 myoblastic cells transfected with a Smad 1 reporter gene construct. Overall our findings indicate that on secretion, gremlin will bind to HS structures on the cell surface and in the extracellular matrix, thus providing for a localised reservoir which can modulate BMP activity in a temporospatially restricted manner. Although binding of heparin/HS to gremlin has been shown elsewhere to be necessary for gremlin activation of VEGFR2, this does not appear to be essential for BMP antagonism by gremlin. Thus these sulfated polysaccharides differentially regulate the activities of gremlin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Kidney Cancer

    MedlinePlus

    ... used to control or reduce symptoms of kidney cancer that has spread to other areas of the body, such as the bones. No complementary and alternative therapies have been proved to successfully treat kidney cancer. ...

  7. Wound Healing in Patients With Impaired Kidney Function.

    PubMed

    Maroz, Natallia; Simman, Richard

    2013-04-01

    Renal impairment has long been known to affect wound healing. However, information on differences in the spectrum of wound healing depending on the type of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with different wound types. On one hand, it follows acute traumatic conditions such as crush injury, burns, and post-surgical wounds, and on the other hand, it arises as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in older people, who have limited physical mobility and predisposition for developing pressure-related wounds. The common risk factors for poor wound healing, generally observed in patients with CKD and ESRD, include poorly controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds related to impaired calcium-phosphorus metabolism, including calciphylaxis, in addition to having the risk factors presented by CKD patients. Overall, there is a wide range of uremic toxins: they may affect local mechanisms of wound healing and also adversely affect the functioning of multiple systems. In the present literature review, we discuss the association between different types of renal impairments and their effects on wound healing and examine this association from different aspects related to the management of wounds in renal impairment patients.

  8. Colistin Use in Patients With Reduced Kidney Function.

    PubMed

    Fiaccadori, Enrico; Antonucci, Elio; Morabito, Santo; d'Avolio, Antonio; Maggiore, Umberto; Regolisti, Giuseppe

    2016-08-01

    Colistin (polymyxin E) is a mainly concentration-dependent bactericidal antimicrobial active against multidrug-resistant Gram-negative bacteria. After being abandoned over the past 30 years due to its neuro- and nephrotoxicity, colistin has been reintroduced recently as a last-resort drug for the treatment of multidrug-resistant Gram-negative bacteria infections in combination with other antimicrobials. Unfortunately, although renal toxicity is a well-known dose-related adverse effect of colistin, relatively few studies are currently available on its peculiar pharmacodynamic/pharmacokinetic properties in clinical settings at high risk for drug accumulation, such as acute or chronic kidney disease. In these specific contexts, the risk for underdosing is also substantial because colistin can be easily removed by dialysis/hemofiltration, especially when the most efficient modalities of renal replacement therapy (RRT) are used in critically ill patients. For this reason, recent recommendations in patients undergoing RRT have shifted toward higher dosing regimens, and therapeutic drug monitoring is advised. This review aims to summarize the main issues related to chemical structure, pharmacodynamics/pharmacokinetics, and renal toxicity of colistin. Moreover, recent data and current recommendations concerning colistin dosing in patients with reduced kidney function, with special regard to those receiving RRT such as dialysis or hemofiltration, are also discussed. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  9. The benefits of estrogen or selective estrogen receptor modulator on kidney and its related disease-chronic kidney disease-mineral and bone disorder: osteoporosis.

    PubMed

    Lee, Wen-Ling; Cheng, Ming-Huei; Tarng, Der-Cherng; Yang, Wu-Chang; Lee, Fa-Kung; Wang, Peng-Hui

    2013-07-01

    An umbrella concept addressing the relationship between chronic kidney disease (CKD) and mineral and bone disorders has been developed in recent years. Given the high prevalence of osteoporosis-related fractures in postmenopausal women with CKD, especially those undergoing chronic hemodialysis, the strategy used in the prevention and management of CKD and its associated osteoporosis in these postmenopausal women has become a topic of substantial debate. This controversy has ongoing relevance because osteoporosis results in a significant economic burden secondary to increased morbidity and mortality. The perfect goal of treatment and prevention includes both bone protection and renal protection, or at least protection of one disease without compromising the other disease. Both CKD and osteoporosis are frequently observed in the same patients, and often have parallel progression in postmenopausal women. Estrogen, the main female hormone during reproductive age, has been reported to have a protective effect on kidney fibrosis in several animal models, and is also considered one of the most effective drugs in the management of postmenopausal women with osteoporosis and prevention of osteoporosis. However, due to the many adverse events associated with the use of estrogen with and without progestin, some of which have contributed to significant morbidity and mortality, drug modification, which has had fewer reported incidences of adverse events without compromising the protective effect on both the kidney and bone, may have an easier road to acceptance. Therapeutic alternatives, such as the selective estrogen receptor modulators (SERMs), have shown the benefits of estrogen on bone, serum lipid levels, and renal protection, without any adverse effects on the breast and endometrium. The Multiple Outcomes of Raloxifene Evaluation trial (MORE) and its extension-Continuing Outcomes Relevant to Evista (CORE), a double-blind, randomized clinical trial encompassing

  10. An Orientation Distribution Function for Trabecular Bone

    SciTech Connect

    Lawrence Livermore National Laboratory

    2004-10-08

    We describe a new method for quantifying the orientation of trabecular bone from three-dimensional images. Trabecular lattices from five human vertebrae were decomposed into individual trabecular elements, and the orientation, mass, and thickness of each element were recorded. Continuous functions that described the total mass (M({var_phi},{theta})) and mean thickness ({tau}({var_phi},{theta})) of all trabeculae as a function of orientation were derived. The results were compared with experimental measurements of the elastic modulus in the three principal anatomic directions. A power law scaling relationship between the anisotropies in mass and elastic modulus was observed; the scaling exponent was 1.41 (R{sup 2} = 0.88). As expected, the preponderance of trabecular mass was oriented along the cranial-caudal direction; on average, there was 3.4 times more mass oriented vertically than horizontally. Moreover, the vertical trabeculae were 30% thicker, on average, than the horizontal trabeculae. The vertical trabecular thickness was inversely related to the connectivity (R{sup 2} = 0.70; p = 0.07), suggesting a possible organization into either few, thick trabeculae or many thin trabeculae. The method, which accounts for the mechanical connectedness of the lattice, provides a rapid way to both visualize and quantify the three-dimensional organization of trabecular bone.

  11. Assessment of Kidney Function After Allograft Transplantation by Texture Analysis.

    PubMed

    Abbasian Ardakani, Ali; Mohammadi, Afshin; Khalili Najafabad, Bahareh; Abolghasemi, Jamileh

    2017-03-01

    Ultrasonography is the preferable imaging technique for monitoring and assessing complications in kidney allograft transplants. Computer-aided diagnostic system based on texture analysis in ultrasonographic imaging is recommended to identify changes in kidney function after allograft transplantation. A total of 61 biopsy-proven kidney allograft recipients (11 rejected and 50 unrejected) were assessed by a computer-aided diagnostic system. Up to 270 statistical texture features were extracted as descriptors for each region of interest in each recipient. Correlations of texture features with serum creatinine level and differences between rejected and unrejected allografts were analyzed. An area under the receiver operating characteristic curve was calculated for each significant texture feature. Linear discriminant analysis was employed to analyze significant features and increase discriminative power. Recipients were classified by the first nearest neighbor classifier. Fourteen texture features had a significant correlation with serum creatinine level and 16 were significantly different between the rejected and unrejected allografts, for which an area under the curve values were in the range of 0.575 for difference entropy S(4,0) to 0.676 for kurtosis. Using all 16 features, linear discriminant analysis indicated higher performance for classification of the two groups with an area under the curve of 0.975, which corresponded to a sensitivity of 90.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 98.0%. Texture analysis was a reliable method, with the potential for characterization, and can help physicians to diagnose kidney failure after transplantation on ultrasonographic imaging.

  12. Nephrectomy (Kidney Removal)

    MedlinePlus

    ... a healthy kidney intended for an organ transplant. Kidney function Most people have two kidneys — fist-sized ... my kidney function need to be monitored? Monitoring kidney function Most people can function well with only ...

  13. Mineral and bone disorder and vascular calcification in patients with chronic kidney disease.

    PubMed

    Peres, Luis Alberto Batista; Pércio, Pedro Paulo Verona

    2014-01-01

    Vascular calcifications has been associated with bone and mineral disorders. The alterations in the serum level of calcium concentrations and phosphate are importants factors implicated in the arterial calcification in chronic kidney disease. The pathogenesis of vascular calcification is a complex mechanism and not completely clear, being able to correspond to an active process of cellular transformation and heterotopic ossification. Beyond the hypercalcemia and hyperphosphatemia, they are involved in this process changes in the metabolism of inhibitors and promoters of calcification such as fetuin A, osteopontin, osteoprotegerin, and matrix gla protein. For the diagnosis of the calcified arterial injury are available several complementary methods, a method of estimate of the cardiovascular risk based on plain radiographs of the lumbar column and another method based on simple x-rays of the pelvis and hands. Below, we will present a review approching the link between vascular calcifications and mineral disorders.

  14. Bone marrow-derived immature myeloid cells are a main source of circulating suPAR contributing to proteinuric kidney disease.

    PubMed

    Hahm, Eunsil; Wei, Changli; Fernandez, Isabel; Li, Jing; Tardi, Nicholas J; Tracy, Melissa; Wadhwani, Shikha; Cao, Yanxia; Peev, Vasil; Zloza, Andrew; Lusciks, Jevgenijs; Hayek, Salim S; O'Connor, Christopher; Bitzer, Markus; Gupta, Vineet; Sever, Sanja; Sykes, David B; Scadden, David T; Reiser, Jochen

    2017-01-01

    Excess levels of protein in urine (proteinuria) is a hallmark of kidney disease that typically occurs in conjunction with diabetes, hypertension, gene mutations, toxins or infections but may also be of unknown cause (idiopathic). Systemic soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor implicated in the onset and progression of chronic kidney disease (CKD), such as focal segmental glomerulosclerosis (FSGS). The cellular source(s) of elevated suPAR associated with future and progressing kidney disease is unclear, but is likely extra-renal, as the pathological uPAR is circulating and FSGS can recur even after a damaged kidney is replaced with a healthy donor organ. Here we report that bone marrow (BM) Gr-1(lo) immature myeloid cells are responsible for the elevated, pathological levels of suPAR, as evidenced by BM chimera and BM ablation and cell transfer studies. A marked increase of Gr-1(lo) myeloid cells was commonly found in the BM of proteinuric animals having high suPAR, and these cells efficiently transmit proteinuria when transferred to healthy mice. In accordance with the results seen in suPAR-associated proteinuric animal models, in which kidney damage is caused not by local podocyte-selective injury but more likely by systemic insults, a humanized xenograft model of FSGS resulted in an expansion of Gr-1(lo) cells in the BM, leading to high plasma suPAR and proteinuric kidney disease. Together, these results identify suPAR as a functional connection between the BM and the kidney, and they implicate BM immature myeloid cells as a key contributor to glomerular dysfunction.

  15. Therapeutic action of bone marrow-derived stem cells against acute kidney injury.

    PubMed

    Liu, Pengfei; Feng, Yetong; Wang, Yi; Zhou, Yulai

    2014-10-12

    Acute kidney injury (AKI) is a frequent clinical disease with a high morbidity rate and mortality rate, while the treatment options for this intractable disease are limited currently. In recent years, bone marrow-derived mesenchymal stem cells (BMSCs) have been demonstrated to hold an effect therapeutic action against AKI by scientists gradually, and the cells are capable to localize to renal compartments and contribute to kidney regeneration though differentiation or paracrine action. Especially, the advantages of BMSCs, such as low toxicity and side effect as well as autologous transplantation, endue the cell with a promising potential in clinical therapy against AKI. In this review, we mainly provide a concise overview of the application of BMSCs in the treatment of AKI, and summarize a series of published data regarding the mechanisms and optimizations of the BMSC-based therapy in renal repair after AKI. Even though some critical points about the BMSC-based therapy model still need clarification, we hope to develop more reliable pharmacological or biotechnical strategies utilizing the stem cell for the eventual treatment of humans with AKI, based on these studies and the understanding of mechanism of renal protection by BMSCs.

  16. Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

    PubMed Central

    Wang, Hao; Guan, Yuxia; Karamercan, Mehmet Akif; Ye, Lan; Bhatti, Tricia; Becker, Lance B.; Baur, Joseph A.; Sims, Carrie A.

    2015-01-01

    Objective Hemorrhagic shock may contribute to acute kidney injury by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin-1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. Method Using a decompensated hemorrhagic shock model, male Long-Evans rats (n=6 per group) were sacrificed prior to hemorrhage (Sham), at severe shock, and following either lactated Ringer’s (LR) Resuscitation or LR+RSV Resuscitation (RSV: 30mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen (BUN) and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (CI, CII, and CIV) using high-resolution respirometry. Total mitochondria reactive oxygen species (ROS) were measured using fluorometry and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. qPCR was used quantify mRNA from PGC1-α, SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Results RSV supplementation during resuscitation restored mitochondrial respiratory capacity, decreased mitochondrial ROS and lipid peroxidation. Compared to standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both SOD2 and catalase expression. Although RSV was associated with decreased lactate production, pH, BUN and serum creatinine values did not differ between resuscitation strategies. Conclusions Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock. PMID:25895148

  17. Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock.

    PubMed

    Wang, Hao; Guan, Yuxia; Karamercan, Mehmet Akif; Ye, Lan; Bhatti, Tricia; Becker, Lance B; Baur, Joseph A; Sims, Carrie A

    2015-08-01

    Hemorrhagic shock may contribute to acute kidney injury (AKI) by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin 1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. Using a decompensated hemorrhagic shock model, male Long-Evans rats (n = 6 per group) were killed prior to hemorrhage (sham), at severe shock, and following either lactated Ringer's (LR) resuscitation or LR + RSV resuscitation (RSV: 30 mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen, and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (complexes I, II, and IV) using high-resolution respirometry. Total mitochondria reactive oxygen species were measured using fluorometry, and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. Quantitative polymerase chain reaction was used quantify mRNA from peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α) SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Resveratrol supplementation during resuscitation restored mitochondrial respiratory capacity and decreased mitochondrial reactive oxygen species and lipid peroxidation. Compared with standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both superoxide dismutase 2 and catalase expression. Although RSV was associated with decreased lactate production, pH, blood urea nitrogen, and serum creatinine values did not differ between resuscitation strategies. Resuscitation with RSV significantly restored renal mitochondrial

  18. Is chronic kidney disease-mineral bone disorder (CKD-MBD) really a syndrome?

    PubMed

    Cozzolino, Mario; Ureña-Torres, Pablo; Vervloet, Marc G; Brandenburg, Vincent; Bover, Jordi; Goldsmith, David; Larsson, Tobias E; Massy, Ziad A; Mazzaferro, Sandro

    2014-10-01

    The concept of chronic kidney disease-mineral bone disorder (CKD-MBD) does not appear to fulfil the requirements for a syndrome at first glance, but its definition has brought some clear-cut benefits for clinicians and patients, including wider and more complex diagnostic and therapeutic approaches to the management of this challenging set of issues. Admittedly, not all components of CKD-MBD are present in all patients at all times, but these are highly interrelated, involving mineral and bone laboratory abnormalities, clinical and histological bone disease and finally, cardiovascular disease. The presence of typical biological bone ossification processes in an ectopic anatomical location in CKD has helped to define the existence of an unprecedented bone-vascular relationship, extending its interest even to other medical specialities. For now, we believe that CKD-MBD does not reach full criteria to be defined as a syndrome. However, this novel concept has clearly influenced current clinical guidelines. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF/KDOQI™) guidelines in 2003 for instance recommended that calcium-based phosphate binders should be avoided to treat hyperphosphataemia in the presence of cardiovascular calcifications. In 2009, the KDIGO and other guidelines reinforced and extended this recommendation by stating that it is reasonable to choose oral phosphate binder therapy by taking into consideration other components of CKD-MBD. Similarly, it is also considered reasonable to use information on vascular/valvular calcification to guide the management of CKD-MBD. Our current assumption as a working group 'CKD-MBD' is that CKD-MBD has the potential to be defined a true syndrome, such as a constellation of concurrent signs and symptoms that suggest a common underlying mechanism for these components as opposed to the term disease. The term 'syndrome' also implies that in any patient at risk due to the presence of one or a few

  19. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  20. Medical multiparametric time course prognoses applied to kidney function assessments.

    PubMed

    Schmidt, R; Pollwein, B; Gierl, L

    1999-01-01

    In this paper, we describe an approach to utilize case-based reasoning methods for trend prognoses for the monitoring of the kidney function in an Intensive Care Unit (ICU) setting. Since using conventional methods for reasoning over time does not fit for course predictions with poor medical knowledge of typical course patterns, we have developed abstraction methods suitable for integration into our case-based reasoning system ICONS. These methods combine medical experience with prognoses of multiparametric courses. On the ICU, the monitoring system NIMON provides a daily report based on current measured and calculated kidney function parameters. Subsequently, we generate course-characteristic trend descriptions of the renal function over the course of time. Using case-based reasoning retrieval methods, we search in the case base for courses similar to the current trend descriptions. Finally, we present the current course together with similar courses as comparisons and as probable prognoses to the user. We applied case-based reasoning methods in a domain which seemed reserved for statistical methods and conventional temporal reasoning.

  1. Role of glutathione transport processes in kidney function

    SciTech Connect

    Lash, Lawrence H. . E-mail: l.h.lash@wayne.edu

    2005-05-01

    The kidneys are highly dependent on an adequate supply of glutathione (GSH) to maintain normal function. This is due, in part, to high rates of aerobic metabolism, particularly in the proximal tubules. Additionally, the kidneys are potentially exposed to high concentrations of oxidants and reactive electrophiles. Renal cellular concentrations of GSH are maintained by both intracellular synthesis and transport from outside the cell. Although function of specific carriers has not been definitively demonstrated, it is likely that multiple carriers are responsible for plasma membrane transport of GSH. Data suggest that the organic anion transporters OAT1 and OAT3 and the sodium-dicarboxylate 2 exchanger (SDCT2 or NaDC3) mediate uptake across the basolateral plasma membrane (BLM) and that the organic anion transporting polypeptide OATP1 and at least one of the multidrug resistance proteins mediate efflux across the brush-border plasma membrane (BBM). BLM transport may be used pharmacologically to provide renal proximal tubular cells with exogenous GSH to protect against oxidative stress whereas BBM transport functions physiologically in turnover of cellular GSH. The mitochondrial GSH pool is derived from cytoplasmic GSH by transport into the mitochondrial matrix and is mediated by the dicarboxylate and 2-oxoglutarate exchangers. Maintenance of the mitochondrial GSH pool is critical for cellular and mitochondrial redox homeostasis and is important in determining susceptibility to chemically induced apoptosis. Hence, membrane transport processes are critical to regulation of renal cellular and subcellular GSH pools and are determinants of susceptibility to cytotoxicity induced by oxidants and electrophiles.

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

    PubMed

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

    2015-09-02

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

  3. Effect of Aerobic Exercise on Markers of Bone Metabolism of Overweight and Obese Patients With Chronic Kidney Disease.

    PubMed

    Gomes, Tarcisio Santana; Aoike, Danilo Takashi; Baria, Flavia; Graciolli, Fabiana G; Moyses, Rosa M A; Cuppari, Lilian

    2017-09-01

    The aim of the study was to investigate the effect of aerobic exercise on markers of bone metabolism in overweight and obese nondialysis-dependent patients with chronic kidney disease. This is a post-hoc study with 39 sedentary patients (55.5 ± 8.3 years, body mass index 31.2 ± 4.4 kg/m(2), estimated glomerular filtration rate 26.9 ± 11.7 mL/minute) who were randomly assigned to the aerobic exercise group (n = 24) or the control group (n = 15). The aerobic training (walking) was prescribed according to ventilatory threshold and was performed 3 times per week during 24 weeks. Carboxylated and undercarboxylated osteocalcin (GLA and GLU), sclerostin and tartrate-resistant acid phosphatase isoform 5b (TRAP-5b), parathyroid hormone, total alkaline phosphatase (AP), body composition, cardiorespiratory, and functional capacity tests were measured at baseline and after the follow-up. At baseline, carboxylated osteocalcin (GLA) and undercarboxylated osteocalcin (GLU) were inversely correlated with estimated glomerular filtration rate (r = -0.64; r = -0.38, respectively). Both osteocalcin fragments were positively correlated with total AP (GLA: r = 0.36; GLU: r = 0.53). An inverse correlation was found between GLA and sclerostin with body fat (r = -0.36; r = -0.46, respectively). GLU was negatively correlated with markers of muscle mass (r = -0.34). TRAP-5b and sclerostin were inversely correlated with 6-minute walk test and time up and go test, respectively (r = -0.34; r = -0.35, respectively). After 24 weeks, all physical capacity parameters increased in the exercise group (P < .001). Except for total AP that increased after 24 weeks in the exercise group (P < .05), no other changes were observed in both groups in relation to the bone metabolism biomarkers investigated. In this post-hoc study, the aerobic training used did not promote relevant changes in the bone metabolism markers investigated. Copyright © 2017 National Kidney

  4. Vascular calcification and bone mineral density in recurrent kidney stone formers.

    PubMed

    Shavit, Linda; Girfoglio, Daniela; Vijay, Vivek; Goldsmith, David; Ferraro, Pietro Manuel; Moochhala, Shabbir H; Unwin, Robert

    2015-02-06

    Recent epidemiologic studies have provided evidence for an association between nephrolithiasis and cardiovascular disease, although the underlying mechanism is still unclear. Vascular calcification (VC) is a strong predictor of cardiovascular morbidity and the hypothesis explored in this study is that VC is more prevalent in calcium kidney stone formers (KSFs). The aims of this study were to determine (1) whether recurrent calcium KSFs have more VC and osteoporosis compared with controls and (2) whether hypercalciuria is related to VC in KSFs. This is a retrospective, matched case-control study that included KSFs attending an outpatient nephrology clinic of the Royal Free Hospital (London, UK) from 2011 to 2014. Age- and sex-matched non-stone formers were drawn from a list of potential living kidney donors from the same hospital. A total of 111 patients were investigated, of which 57 were KSFs and 54 were healthy controls. Abdominal aortic calcification (AAC) and vertebral bone mineral density (BMD) were assessed using available computed tomography (CT) imaging. The prevalence, severity, and associations of AAC and CT BMD between KSFs and non-stone formers were compared. Mean age was 47±14 years in KSFs and 47±13 in non-stone formers. Men represented 56% and 57% of KSFs and non-stone formers, respectively. The prevalence of AAC was similar in both groups (38% in KSFs versus 35% in controls, P=0.69). However, the AAC severity score (median [25th percentile, 75th percentile]) was significantly higher in KSFs compared with the control group (0 [0, 43] versus 0 [0, 10], P<0.001). In addition, the average CT BMD was significantly lower in KSFs (159±53 versus 194 ±48 Hounsfield units, P<0.001). A multivariate model adjusted for age, sex, high BP, diabetes, smoking status, and eGFR confirmed that KSFs have higher AAC scores and lower CT BMD compared with non-stone formers (P<0.001 for both). Among stone formers, the association between AAC score and hypercalciuria was

  5. Impact of kidney function and urinary protein excretion on pulmonary function in Japanese patients with chronic kidney disease.

    PubMed

    Nakade, Yusuke; Toyama, Tadashi; Furuichi, Kengo; Kitajima, Shinji; Ohkura, Noriyuki; Sagara, Akihiro; Shinozaki, Yasuyuki; Hara, Akinori; Kitagawa, Kiyoki; Shimizu, Miho; Iwata, Yasunori; Oe, Hiroyasu; Nagahara, Mikio; Horita, Hiroshi; Sakai, Yoshio; Kaneko, Shuichi; Wada, Takashi

    2014-10-01

    Although the cardiorenal relationship in chronic kidney disease has been investigated, information about the lung-kidney relationship is limited. Here, we investigated the impact of kidney function and urinary protein excretion on pulmonary dysfunction. The data from pulmonary function tests and kidney function (estimated glomerular filtration rate [eGFR] and urinary protein) between 1 April 2005 and 30 June 2010 were selected from our laboratory database. Data were classified into 4 categories according to eGFR and proteinuria. Category 1, eGFR ≥60 ml/min/1.73 m(2) and urinary protein <0.3 g/gCr; category 2, eGFR <60 ml/min/1.73 m(2) and urinary protein <0.3 g/gCr; category 3, eGFR ≥60 ml/min/1.73 m(2) and urinary protein ≥0.3 g/gCr; and category 4, eGFR <60 ml/min/1.73 m(2) and urinary protein ≥0.3 g/gCr. Pulmonary function data were evaluated according to these 4 categories. A total of 133 participants without major respiratory disease, abnormal computed tomography and smoking history were enrolled. Hemoglobin (Hb)-adjusted percentage carbon monoxide diffusing capacity (%DLCO) in category 4 (46.2 ± 7.5) and category 2 (63.6 ± 17.8) were significantly lower than in category 1 (75.8 ± 18.9) (P < 0.05). In addition, Hb-adjusted %DLCO was weakly correlated with eGFR in participants with urinary protein <0.3 g/gCr (R = 0.30, P = 0.001). Hb-adjusted %DLCO was strongly correlated with eGFR in participants with urinary protein ≥0.3 g/gCr (R = 0.81, P < 0.001). Other pulmonary function test markers (percentage (%) vital capacity, % forced expiratory volume in one second (FEV1), FEV1/forced vital capacity, % total lung capacity, and % residual volume) were not significantly different between categories. This study suggests that decreased eGFR is associated with decreased %DLCO in proteinuric patients.

  6. Smell and taste function in children with chronic kidney disease.

    PubMed

    Armstrong, Jessica E; Laing, David G; Wilkes, Fiona J; Kainer, Gad

    2010-08-01

    Loss of appetite and poor growth are common in children with chronic kidney disease (CKD), and changes in smell and/or taste function may be responsible, but the hypothesis has not been proven. This aims of this prospective age- and gender-controlled study were to determine whether: (1) changes in smell and taste function occur in children with CKD; (2) smell or taste dysfunction are associated with estimated glomerular filtration rate (eGFR); (3) there is an association between smell or taste loss and body mass index (BMI). The study cohort consisted of 72 children of whom 20 were CKD stage 3-5 patients, 12 were CKD stage 2 patients, 20 were clinical controls (CC) and 20 were healthy children (HC). The CKD patients and clinical controls were recruited from Sydney Children's Hospital and The Children's Hospital, Westmead, and healthy controls were recruited from a local school. Scores for each group from taste and smell chemosensory function tests were compared, and their relationship with renal function and BMI investigated. The CKD stage 3-5 group had a significantly lower taste identification score (85.6%, P < 0.001) than the CC (94.8%) and HC (94.8%) groups, with almost one third of the children in the CKD stage 3-5 group exhibiting taste loss. Decreased taste function was associated with decreased eGFR (r = 0.43, P < 0.01), but no association between BMI and taste function was found (r = 0.001, P > 0.9). Odour identification scores were not different; however, there was a positive relationship with BMI (r = 0.427, P = 0.006). We conclude that a loss of taste can occur in children with CKD and that when it occurs, it worsens as eGFR declines and is found early in kidney disease.

  7. Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis

    PubMed Central

    Malaval, Luc; Wade-Guéye, Ndéyé Marième; Boudiffa, Maya; Fei, Jia; Zirngibl, Ralph; Chen, Frieda; Laroche, Norbert; Roux, Jean-Paul; Burt-Pichat, Brigitte; Duboeuf, François; Boivin, Georges; Jurdic, Pierre; Lafage-Proust, Marie-Hélène; Amédée, Joëlle; Vico, Laurence; Rossant, Janet; Aubin, Jane E.

    2008-01-01

    Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (−/−) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP−/− mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (≥12 mo) BSP−/− mice. At 4 mo, BSP−/− mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP−/− versus WT bone marrow stromal cultures. BSP−/− hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP−/− mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN−/− mice. PMID:18458111

  8. 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.

  9. Association of Serum Osteoprotegerin Levels with Bone Loss in Chronic Kidney Disease: Insights from the KNOW-CKD Study

    PubMed Central

    Kim, Chang Seong; Bae, Eun Hui; Ma, Seong Kwon; Han, Seung Hyeok; Choi, Kyu Hun; Lee, Joongyub; Chae, Dong Wan; Oh, Kook-Hwan; Ahn, Curie; Kim, Soo Wan

    2016-01-01

    Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density. This study examined the association between serum osteoprotegerin levels and bone loss in patients with chronic kidney disease, a condition associated with increased risk of mineral and bone disorders. The bone mineral densities of the lumbar spine, total hip, and femur neck were assessed by dual-energy X-ray absorptiometry; serum osteoprotegerin levels were measured at baseline for 1,423 patients enrolled in the prospective KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Patients aged ≥50 years and with a T-score ≤ –2.5 were diagnosed as having osteoporosis. Multivariable linear regression analysis indicated independent association between serum osteoprotegerin levels and decreased bone mineral density in the lumbar spine (B: –0.489, 95% confidence interval [CI]: –0.883 to –0.095, P = 0.015), and total hip (B: –0.349, 95% CI: –0.672 to –0.027, P = 0.027). However, bone mineral density of the femur neck was not associated with serum osteoprotegerin levels in women. After adjustments, no independent association was found between serum osteoprotegerin levels and bone mineral density in men. In multivariable logistic regression analysis, serum osteoprotegerin levels were associated with increased risk of osteoporosis in women (odds ratio [OR]: 4.72, 95% CI: 1.35 to 16.52, P = 0.015), but not in men (OR: 0.21; 95% CI: 0.04 to 1.31, P = 0.095). To summarize, in female patients with chronic kidney disease, increased serum osteoprotegerin levels were independently associated with decreased bone mineral density in the lumbar spine and total hip, and with increased risk of osteoporosis. Therefore, the measurement of serum osteoprotegerin concentration might be useful as a surrogate marker for determining bone loss in patients with chronic kidney disease, especially for women, although not so

  10. Nitrate Supplementation, Exercise, and Kidney Function: Are There Detrimental Effects?

    PubMed

    Carpentier, Alain; Stragier, Séverine; Bréjeon, Camille; Poortmans, Jacques R

    2015-07-01

    Recently, dietary supplementation with inorganic nitrate (NO3) has been proposed to endurance athletes to increase their performance. However, it has been suggested that an excess of NO3 might be harmful. The present study analyzed the effect of NO3 supplementation on kidney function. Thirteen young male subjects performed a 20-min cycling exercise at 85% of the maximal oxygen capacity. Seven days before exercise, the subjects ingested either a placebo (Pl) or 450 mg of potassium nitrate (PN) per day. Venous blood samples and urine collections were collected before and immediately after exercise and after 60 min of recovery. Glomerular filtration rates (GFR) and clearances (Cl) were calculated from serum content and urine output for creatinine (Crn), albumin (Alb), and urea. Under resting conditions, GFR and all clearance measures did not differ between Pl and PN. Immediately after exercise, GFR remained stable in both Pl and PN, whereas Cl-urea decreased significantly (P < 0.05) in Pl (-44%) and PN (-49%). Alb urine outputs were enhanced by 18- to 20-fold in Pl and PN, respectively (P < 0.05). After the recovery period, GFR remained enhanced under Pl conditions, whereas Cl-urea returned to initial values in placebo and nitrate supplementation. Alb output and Cl-Alb remained enhanced under PN conditions. These results mainly indicate that dietary nitrate supplementation over a week does not induce any specific kidney function modifications either at rest or during sustained submaximal exercise as compared with Pl.

  11. The regulation and function of microRNAs in kidney diseases.

    PubMed

    Wei, Qingqing; Mi, Qing-Sheng; Dong, Zheng

    2013-07-01

    MicroRNAs (miRNA) are endogenous short noncoding RNAs, which regulate virtually all major cellular processes by inhibiting target gene expression. In kidneys, miRNAs have been implicated in renal development, homeostasis, and physiological functions. In addition, miRNAs play important roles in the pathogenesis of various renal diseases, including renal carcinoma, diabetic nephropathy, acute kidney injury, hypertensive nephropathy, polycystic kidney disease, and others. Furthermore, miRNAs may have great values as biomarkers in different kidney diseases.

  12. Decreased kidney function among agricultural workers in El Salvador.

    PubMed

    Peraza, Sandra; Wesseling, Catharina; Aragon, Aurora; Leiva, Ricardo; García-Trabanino, Ramón Antonio; Torres, Cecilia; Jakobsson, Kristina; Elinder, Carl Gustaf; Hogstedt, Christer

    2012-04-01

    An epidemic of chronic kidney disease of unknown cause has emerged along the Pacific coast of Central America, particularly in relatively young male sugarcane workers. In El Salvador, we examined residence and occupations at different altitudes as surrogate risk factors for heat stress. Cross-sectional population-based survey. Populations aged 20-60 years of 5 communities in El Salvador, 256 men and 408 women (participation, 73%): 2 coastal communities with current sugarcane and past cotton production and 3 communities above 500 m with sugarcane, coffee, and service-oriented economies. Participant sex, age, residence, occupation, agricultural history by crop and altitude, and traditional risk factors for CKD. Serum creatinine (SCr) level greater than the normal laboratory range for sex, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and proteinuria categorized as low (protein excretion ≥ 30-< 300 mg/dL) and high grade (≥ 300 mg/dL). Of the men in the coastal communities, 30% had elevated SCr levels and 18% had eGFR < 60 mL/min/1.73 m2 compared with 4% and 1%, respectively, in the communities above 500 m. For agricultural workers, prevalences of elevated SCr levels and eGFR < 60 mL/min/1.73 m2 were highest for coastal sugarcane and cotton plantation workers, but were not increased in sugarcane workers at 500 m or subsistence farmers. Women followed a weaker but similar pattern. Proteinuria was infrequent, of low grade, and not different among communities, occupations, or sexes. The adjusted ORs of decreased kidney function for 10-year increments of coastal sugarcane or cotton plantation work were 3.1 (95% CI, 2.0-5.0) in men and 2.3 (95% CI, 1.4-3.7) in women. The cross-sectional nature of the study limits etiologic interpretations. Agricultural work on lowland sugarcane and cotton plantations was associated with decreased kidney function in men and women, possibly related to strenuous work in hot environments with repeated volume depletion

  13. 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.

  14. 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

    2017-05-22

    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 in 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 other 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 other group. In our study, about 10% of patients had bone fractures in two-year follow-up period. Patients who developed fractures had a higher PTH level and FRAX score.

  15. 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

    2017-08-07

    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.

  16. Biosignals analysis for kidney function effect analysis of fennel aromatherapy.

    PubMed

    Kim, Bong-Hyun; Cho, Dong-Uk; Seo, Ssang-Hee

    2015-01-01

    Human effort in order to enjoy a healthy life is diverse. IT technology to these analyzes, the results of development efforts, it has been applied. Therefore, I use the care and maintenance diagnostic health management and prevention than treatment. In particular, the aromatherapy treatment easy to use without the side effects there is no irritation, are widely used in modern society. In this paper, we measured the aroma effect by applying a biosignal analysis techniques; an experiment was performed to analyze. In particular, we design methods and processes of research based on the theory aroma that affect renal function. Therefore, in this paper, measuring the biosignals and after fennel aromatherapy treatment prior to the enforcement of the mutual comparison, through the analysis, studies were carried out to analyze the effect of fennel aromatherapy therapy on kidney function.

  17. Biosignals Analysis for Kidney Function Effect Analysis of Fennel Aromatherapy

    PubMed Central

    Kim, Bong-Hyun; Cho, Dong-Uk; Seo, Ssang-Hee

    2015-01-01

    Human effort in order to enjoy a healthy life is diverse. IT technology to these analyzes, the results of development efforts, it has been applied. Therefore, I use the care and maintenance diagnostic health management and prevention than treatment. In particular, the aromatherapy treatment easy to use without the side effects there is no irritation, are widely used in modern society. In this paper, we measured the aroma effect by applying a biosignal analysis techniques; an experiment was performed to analyze. In particular, we design methods and processes of research based on the theory aroma that affect renal function. Therefore, in this paper, measuring the biosignals and after fennel aromatherapy treatment prior to the enforcement of the mutual comparison, through the analysis, studies were carried out to analyze the effect of fennel aromatherapy therapy on kidney function. PMID:25977696

  18. Emerging role of autophagy in kidney function, diseases and aging.

    PubMed

    Huber, Tobias B; Edelstein, Charles L; Hartleben, Björn; Inoki, Ken; Jiang, Man; Koya, Daisuke; Kume, Shinji; Lieberthal, Wilfred; Pallet, Nicolas; Quiroga, Alejandro; Ravichandran, Kameswaran; Susztak, Katalin; Yoshida, Sei; Dong, Zheng

    2012-07-01

    Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy.

  19. Kidney Disease

    MedlinePlus

    ... version of this page please turn Javascript on. Kidney Disease What is Kidney Disease? What the Kidneys Do Click for more information You have two ... damaged, wastes can build up in the body. Kidney Function and Aging Kidney function may be reduced ...

  20. 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

  1. Mineral and bone disorders in chronic kidney disease and end-stage renal disease patients: new insights into vitamin D receptor activation

    PubMed Central

    Bover, Jordi; Cozzolino, Mario

    2011-01-01

    Progressive loss of kidney function leads to reduced production of calcitriol (1,25-dihydroxyvitamin D; active vitamin D) and an imbalance in serum calcium (Ca) and phosphorus (P) levels, which are associated with progression of renal failure as well as increased rates of cardiovascular (CV) events and mortality. In addition, multifactorial hypocalcemia and resistance to parathyroid hormone (PTH) can lead to prolonged and excessive synthesis and secretion of PTH, eventually leading to development of secondary hyperparathyroidism and renal osteodystrophy. These changes associated with chronic kidney disease (CKD), extending beyond bone and related biochemical abnormalities, have prompted the development of the term CKD–mineral and bone disorder to describe its systemic nature. Excessive P loading, among other factors, will promote vascular calcification (VC), and PTH production will affect bone remodeling. Although administration of calcitriol increases serum Ca levels and decreases PTH, it is also associated with elevated Ca × P product. Therefore, compounds that selectively activate vitamin D receptors (VDR activators), potentially reducing Ca–P toxicity and distinctly affecting pathogenic mechanisms of VC, might enhance CV and renal protection, increase the vitamin D therapeutic window, and thus provide a significant clinical benefit. Moreover, selective VDR activators have been associated with improvement in survival, at least among dialysis patients. Thus, selective VDR activators should be considered a novel and interesting approach to enhance the standard of care in CKD patients. PMID:25018911

  2. [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.

  3. Comparative analyses of B cell populations in trout kidney and mouse bone marrow; establishing “B cell signatures”

    PubMed Central

    Zwollo, Patty; Mott, Katrina; Barr, Maggie

    2010-01-01

    This study aimed to identify the frequency and distribution of developing B cell populations in the kidney of the rainbow trout, using four molecular B cell markers that are highly conserved between species, including two transcription factors, Pax5 and EBF1, recombination activating gene RAG1, and the immunoglobulin heavy chain mu. Three distinct B cell stages were defined: early developing B cells (CLP, pro-B, and early pre-B cells), late developing B cell (late pre-B, immature B, and mature B cells), and IgM-secreting cells. Developmental stage-specific, combinatorial expression of Pax5, EBF1, RAG1 and immunoglobulin mu was determined in trout anterior kidney cells by flow cytometry. Trout staining patterns were compared to a well-defined primary immune tissue, mouse bone marrow, and using mouse surface markers B220 and CD43. A remarkable level of similarity was uncovered between the primary immune tissues of both species. Subsequent analysis of the entire trout kidney, divided into five contiguous segments K1-K5, revealed a complex pattern of early developing, late developing, and IgM-secreting B cells. Patterns in anterior kidney segment K1 were most similar to those of mouse bone marrow, while the most posterior part of the kidney, K5, had many IgM-secreting cells, but lacked early developing B cells. A potential second B lymphopoiesis site was uncovered in segment K4 of the kidney. The B cell patterns, or “B cell signatures” described here provide information on the relative abundance of distinct developing B cell populations in the trout kidney, and can be used in future studies on B cell development in other vertebrate species. PMID:20705088

  4. Basic fibroblast growth factor reduces functional and structural damage in chronic kidney disease.

    PubMed

    Villanueva, Sandra; Contreras, Felipe; Tapia, Andrés; Carreño, Juan E; Vergara, Cesar; Ewertz, Ernesto; Cespedes, Carlos; Irarrazabal, Carlos; Sandoval, Mauricio; Velarde, Victoria; Vio, Carlos P

    2014-02-15

    Chronic kidney disease (CKD) is characterized by loss of renal function. The pathological processes involved in the progression of this condition are already known, but the molecular mechanisms have not been completely explained. Recent reports have shown the intrinsic capacity of the kidney to undergo repair after acute injury through the reexpression of repairing proteins (Villanueva S, Cespedes C, Vio CP. Am J Physiol Regul Integr Comp Physiol 290: R861-R870, 2006). Stimulation with basic fibroblast growth factor (bFGF) could accelerate this process. However, it is not known whether bFGF can induce this phenomenon in kidney cells affected by CKD. Our aim was to study the evolution of renal damage in animals with CKD treated with bFGF and to relate the amount of repairing proteins with renal damage progression. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy (NPX) and treated with bFGF (30 μg/kg, NPX+bFGF); a control NPX group was treated with saline (NPX+S). Animals were euthanized 35 days after bFGF administration. Functional effects were assessed based on serum creatinine levels; morphological damage was assessed by the presence of macrophages (ED-1), interstitial α-smooth muscle actin (α-SMA), and interstitial collagen through Sirius red staining. The angiogenic factors VEGF and Tie-2 and the epithelial/tubular factors Ncam, bFGF, Pax-2, bone morphogenic protein-7, Noggin, Lim-1, Wnt-4, and Smads were analyzed. Renal stem cells were evaluated by Oct-4. We observed a significant reduction in serum creatinine levels, ED-1, α-SMA, and Sirius red as well as an important induction of Oct-4, angiogenic factors, and repairing proteins in NPX+bFGF animals compared with NPX+S animals. These results open new perspectives toward reducing damage progression in CKD.

  5. Rapid Kidney Function Decline and Mortality Risk in Older Adults

    PubMed Central

    Rifkin, Dena E.; Shlipak, Michael G.; Katz, Ronit; Fried, Linda F.; Siscovick, David; Chonchol, Michel; Newman, Anne B.; Sarnak, Mark J.

    2010-01-01

    Background Impaired kidney function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality in older adults. Methods The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFRcreat) and cystatin C (eGFRcys) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m2 per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up. Results Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFRcreat and eGFRcys were 79 (23) mL/min/1.73 m2 and 79 (19) mL/min/1.73 m2, respectively. Individuals with rapid decline measured by eGFRcreat (n=714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40–2.06) and all-cause (AHR, 1.73; 95% CI, 1.54–1.94) mortality. Individuals with rapid decline measured by eGFRcys (n=1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29–1.80) and all-cause (AHR, 1.53; 95% CI, 1.38–1.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, race, or prevalent coronary heart disease. Conclusion Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables. PMID:19001197

  6. Adipose-Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology

    PubMed Central

    Bodle, Josephine C.; Hanson, Ariel D.

    2011-01-01

    This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application. PMID:21338267

  7. Tensile properties of rat femoral bone as functions of bone volume fraction, apparent density and volumetric bone mineral density.

    PubMed

    Nazarian, Ara; Araiza Arroyo, Francisco J; Rosso, Claudio; Aran, Shima; Snyder, Brian D

    2011-09-02

    Mechanical testing has been regarded as the gold standard to investigate the effects of pathologies on the structure-function properties of the skeleton. Tensile properties of cancellous and cortical bone have been reported previously; however, no relationships describing these properties for rat bone as a function of volumetric bone mineral density (ρ(MIN)), apparent density or bone volume fraction (BV/TV) have been reported in the literature. We have shown that at macro level, compression and torsion properties of rat cortical and cancellous bone can be well described as a function of BV/TV, apparent density or ρ(MIN) using non-destructive micro-computed tomographic imaging and mechanical testing to failure. Therefore, the aim of this study is to derive a relationship expressing the tensile properties of rat cortical bone as a function of BV/TV, apparent density or ρ(MIN) over a range of normal and pathologic bones. We used bones from normal, ovariectomized and osteomalacic animals. All specimens underwent micro-computed tomographic imaging to assess bone morphometric and densitometric indices and uniaxial tension to failure. We obtained univariate relationships describing 74-77% of the tensile properties of rat cortical bone as a function of BV/TV, apparent density or ρ(MIN) over a range of density and common skeletal pathologies. The relationships reported in this study can be used in the structural rigidity to provide a non-invasive method to assess the tensile behavior of bones affected by pathology and/or treatment options.

  8. Efficacy and Safety of Bisphosphonates for Low Bone Mineral Density After Kidney Transplantation

    PubMed Central

    Kan, Shun-Li; Ning, Guang-Zhi; Chen, Ling-Xiao; Zhou, Yong; Sun, Jing-Cheng; Feng, Shi-Qing

    2016-01-01

    Abstract In patients with low bone mineral density (BMD) after kidney transplantation, the role of bisphosphonates remains unclear. We performed a systematic review and meta-analysis to investigate the efficacy and safety of bisphosphonates. We retrieved trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception through May 2015. Only randomized controlled trials that compared bisphosphonate-treated and control groups of patients with low bone mineral density after kidney transplantation were included. The primary outcomes were the percent change in BMD, the absolute change in BMD, and the BMD at the end of study at the lumbar spine. The results were expressed as the mean difference (MD) or relative risk (RR) with the 95% confidence interval (CI). We used a random-effects model to pool the outcomes. We included 17 randomized controlled trials with 1067 patients. Only 1 included trial was found to be at low risk of bias. The rest of the included studies were found to have high to uncertain risk of bias. Compared with the control group, those who received bisphosphonates had a significant increase in percent change in BMD (mean difference [MD] = 5.51, 95% confidence interval [CI] 3.22–7.79, P < 0.00001) and absolute change in BMD (MD = 0.05, 95% CI 0.04–0.05, P < 0.00001), but a nonsignificant increase in BMD at the end of the study (MD = 0.02, 95% CI −0.01 to 0.05, P = 0.25) at the lumbar spine. Bisphosphonates resulted in a significant improvement in percent change in BMD (MD = 4.95, 95% CI 2.57–7.33, P < 0.0001), but a nonsignificant improvement in absolute change in BMD (MD = 0.03, 95% CI −0.00 to 0.06, P = 0.07) and BMD at the end of the study (MD = −0.01, 95% CI −0.04 to 0.02, P = 0.40) at the femoral neck. No significant differences were found in vertebral fractures, nonvertebral fractures, adverse events, and gastrointestinal adverse events

  9. Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III–V, and ESRD

    PubMed Central

    Saad, Marc; Karam, Boutros; Faddoul, Geovani; Douaihy, Youssef El; Yacoub, Harout; Baydoun, Hassan; Boumitri, Christine; Barakat, Iskandar; Saifan, Chadi; El-Charabaty, Elie; Sayegh, Suzanne El

    2016-01-01

    Patients with chronic kidney disease (CKD) are three times more likely to have myocardial infarction (MI) and suffer from increased morbidity and higher mortality. Traditional and unique risk factors are prevalent and constitute challenges for the standard of care. However, CKD patients have been largely excluded from clinical trials and little evidence is available to guide evidence-based treatment of coronary artery disease in patients with CKD. Our objective was to assess whether a difference exists in the management of MI (ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction) among patients with normal kidney function, CKD stage III–V, and end-stage renal disease (ESRD) patients. We conducted a retrospective cohort study on patients admitted to Staten Island University Hospital for the diagnosis of MI between January 2005 and December 2012. Patients were assigned to one of three groups according to their kidney function: Data collected on the medical management and the use of statins, platelet inhibitors, beta-blockers, and angiotensin converting enzyme inhibitors/angiotensin receptor blockers were compared among the three cohorts, as well as medical interventions including: catheterization and coronary artery bypass graft (CABG) when indicated. Chi-square test was used to compare the proportions between nominal variables. Binary logistic analysis was used in order to determine associations between treatment modalities and comorbidities, and to account for possible confounding factors. Three hundred and thirty-four patients (mean age 67.2±13.9 years) were included. In terms of management, medical treatment was not different among the three groups. However, cardiac catheterization was performed less in ESRD when compared with no CKD and CKD stage III–V (45.6% vs 74% and 93.9%) (P<0.001). CABG was performed in comparable proportions in the three groups and CABG was not associated with the degree of CKD (P=0.078) in

  10. Erdheim-Chester disease: a case report with pulmonary, kidney involvement and bone lesions.

    PubMed

    Mounach, Aziza; Nouijai, Abderrzak; Achemlal, Lahsen; El Maghraoui, Abdellah; Bezza, Ahmed

    2010-03-01

    We report the case of a 42-year-old woman who was admitted in 2002 for exploration of diffuse bone pain. She had medical history of pulmonary tuberculosis. Her current symptoms had started 9 months earlier and consisted of bone pain, affecting the legs. She had asthenia and weight loss. At admission, physical examination showed bilateral and symmetrical long bone pain, especially the knees and the ankles. Physical exam was normal elsewhere. Laboratory tests showed inflammation, with an erythrocyte sedimentation rate of 90 mm/h and C-reactive protein 8 mg/l. Protein electrophoresis, red and white blood cell count, renal, and liver function tests were normal. Serum calcium, phosphorus, and urinary calcium were normal. Radiographs showed multiple mixed bone lesions with sclerotic and lytic areas of the femora, tibiae, humerus. Chest radiographs and thoracic computed tomography (CT) scan showed pulmonary fibrosis. Biopsy of the tibial area displayed foamy lipid-laden histiocytes, confirming the diagnosis of Erdheim-Chester disease. Patient was treated with prednisolone plus cyclophosphamide. Her clinical condition improved remarkably during 4 years, but she developed acute renal failure leading to death.

  11. Native kidney function after renal transplantation combined with other solid organs in preemptive patients.

    PubMed

    Mosconi, G; Panicali, L; Persici, E; Conte, D; Cappuccilli, M L; Cuna, V; Capelli, I; Todeschini, P; D'Arcangelo, G Liviano; Stefoni, S

    2010-05-01

    Kidney transplantations combined with other solid organs are progressively increasing in number. There are no guidelines regarding the nephrologic indications for combined transplantations, namely liver-kidney (LKT), or heart-kidney (HKT), in preemptive patients with chronic kidney failure who are not on regular dialysis therapy. The objective of this study was to assess the functional contribution of the native kidneys after preemptive kidney transplantation combined with other solid organs. From 2004, 9 patients (aged 50.3 +/- 8.5 years) with chronic kidney failure (creatinine 2.5 +/- 1.0 mg/dL) caused by polycystic kidney disease (n = 4), vascular nephropathy (n = 2), interstitial nephropathy (n = 1), glomerulonephritis (n = 1), or end-stage kidney disease (n = 1), underwent combined transplantations (8 LKT, 1 HKT). A scintigraphic functional study (Tc-99DMSA or Tc-99mMAG3), was performed at 4 +/- 3 months after transplantation to evaluate the functional contribution of both the native kidneys and the graft. All patients were given immunosuppressive drugs, including a calcineurin inhibitor (tacrolimus/or cyclosporine). At the time of scintigraphy, renal function in all patients was 1.3 +/- 0.3 mg/dL. The functional contribution of the transplanted kidneys was on average 77 +/- 18%. Only in 1 patient was the contribution of the graft <50%. At follow-up after 36 months, patient and kidney survivals were 100%. The study confirmed a high risk of loss of native kidney function in the presence of organic nephropathy. In light of our experience, a creatinine clearance <30 mL/min in an appropriate cutoff for a combined transplantation. Close clinical and instrumental assessment pretransplant is essential before proceeding with a combined transplant program to exclude functional forms and to optimize the use of organs.

  12. Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?

    PubMed Central

    Filgueira, Agostinho; Carvalho, Aluizio Barbosa; Tomiyama, Cristiane; Higa, Andrea; Rochitte, Carlos E.; Santos, Raul D.

    2011-01-01

    Summary Background and objectives Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD. Design, setting, participants, & measurements Seventy-two nondialyzed CKD patients (age 52 ± 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 ± 18.2 ml/min per 1.73 m2) were studied. VBD and CAC were quantified by computed tomography. Results CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score ≥ 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 ± 52 Hounsfield units) correlated inversely with age (r = −0.41, P < 0.001) and calcium score (r = −0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC. Conclusions Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD. PMID:21617086

  13. Feeding flaxseed oil but not secoisolariciresinol diglucoside results in higher bone mass in healthy rats and rats with kidney disease.

    PubMed

    Weiler, H A; Kovacs, H; Nitschmann, E; Bankovic-Calic, N; Aukema, H; Ogborn, M

    2007-05-01

    Flaxseed's oil and lignan, secoisolariciresinol diglucoside (SDG), are implicated in attainment of health and treatment of renal injury and osteoporosis. To test for these benefits, weanling Han:SPRD-cy rats (n=171) with or without kidney disease were randomized to diets made with either corn oil or flaxseed oil and with or without SDG for 12 weeks. In females, weight was lower with the SDG diet. In males fed flaxseed oil, lean mass was higher and fat % was lower. In both sexes, fat % was lower in diseased rats. Bone mineral content (BMC) and density were higher in rats fed flaxseed oil and lower in diseased rats, additionally; BMC was lower in SDG-supplemented females. The benefit of flaxseed oil on body composition is sex specific but the effect on bone mass is not. Lastly, reduced weight due to early rat kidney disease is not due to loss of lean body mass.

  14. Development of Reduced Kidney Function in Rheumatoid Arthritis

    PubMed Central

    Hickson, LaTonya J.; Crowson, Cynthia S.; Gabriel, Sherine E.; McCarthy, James T.; Matteson, Eric L.

    2014-01-01

    Background Rheumatoid arthritis (RA) is associated with a variety of kidney disorders. However, it is unclear whether the development of reduced kidney function (RKF) is higher in patients with RA compared to the general population. Study Design Retrospective review. Setting & Participants Incident adult-onset RA cases (813) and a comparison cohort of non-RA subjects (813) in Olmsted County, Minnesota, from 1980-2007. Predictor Baseline demographic and clinical variables. Outcomes RKF: 1) Estimated GFR (eGFR) <60 ml/min/1.73m2 and 2) eGFR <45 on two consecutive occasions at least 90 days apart; cardiovascular disease (CVD);, and death. Measurements The cumulative incidence of RKF was estimated adjusting for the competing risk of death. Results Of 813 RA patients and 813 non-RA subjects, mean age was 56±16 (SD) years, 68% were female, and 9% had RKF at baseline. The 20-year cumulative incidence of RKF was higher in RA patients compared to non-RA participants for eGFR <60 ml/min/1.73m2 (25% vs. 20%; p=0.03) but not eGFR <45 ml/min/1.73m2 (9% vs. 10%; p=0.8). The presence of CVD at baseline (HR, 1.77; 95% CI, 1.14-2.73; p=0.01) and elevated erythrocyte sedimentation rate in RA patients (HR per 10-mm/h greater, 1.08; 95% CI, 1.00-1.16; p=0.04) was associated with increased risk of eGFR <60 ml/min/1.73m2. An eGFR <60 ml/min/1.73m2 was not associated with an increased risk of CVD development in RA patients (HR, 0.99; 95% CI, 0.63-1.57; p=0.9), however, a greater reduction in GFR (eGFR <45 ml/min/1.73m2) was associated with an increased risk of CVD (HR, 1.93; CI, 1.04-3.58; p=0.04). Limitations RKF was defined by estimating equations for kidney function. We are limited to deriving associations from our findings. Conclusions RA patients were more likely to develop RKF over time. CVD and associated factors appear to play a role. The presence of RA in individuals with RKF may lead to an increase in morbidity from CVD development, for which awareness may provide a means for

  15. Tumor necrosis factor-alpha, Kidney function and hypertension.

    PubMed

    Mehaffey, Eamonn; Majid, Dewan Syed Abdul

    2017-07-19

    Hypertension is considered to be a low-grade inflammatory condition characterized by the presence of various pro-inflammatory cytokines. The inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α) is a constituent of the pro-inflammatory environment that is associated with salt-sensitive hypertension (SSH) and related renal injury. Elevated angiotensin II (AngII) and other factors such as oxidative stress conditions promote TNF-α formation. Many recent studies have provided evidence that TNF-α exerts a direct renal action by regulating hemodynamic and excretory function in the kidney. The cytokine incites a strong natriuretic response and plays a part in regulation of the intrarenal renin-angiotensin system. The exact mechanistic role of TNF-α in the development of SSH is yet poorly understood. While TNF-α antagonism has been shown to attenuate hypertensive responses in many hypertensive animal models, contrasting findings demonstrate that the direct systemic administration of TNF-α usually induces hypotensive as well as natriuretic responses, indicating a counter-regulatory role of TNF-α in SSH. Differential activities of two cell surfaced receptors of TNF-α (receptor type 1 and type 2) may explain the contradictory functions of TNF-α in the setting of hypertension. This mini-review will evaluate ongoing research studies that investigate the action of TNF-α within the kidney and its role as an influential pathophysiologic variable in the development of SSH and renal injury. This information may help to develop specific TNF-α receptor targeting as an effective treatment strategy in this clinical condition. Copyright © 2016, American Journal of Physiology-Renal Physiology.

  16. Kidney Function and Cerebral Blood Flow: The Rotterdam Study.

    PubMed

    Sedaghat, Sanaz; Vernooij, Meike W; Loehrer, Elizabeth; Mattace-Raso, Francesco U S; Hofman, Albert; van der Lugt, Aad; Franco, Oscar H; Dehghan, Abbas; Ikram, M Arfan

    2016-03-01

    CKD is linked with various brain disorders. Whereas brain integrity is dependent on cerebral perfusion, the association between kidney function and cerebral blood flow has yet to be determined. This study was performed in the framework of the population-based Rotterdam Study and included 2645 participants with mean age of 56.6 years (45% men). We used eGFR and albumin-to-creatinine ratio to assess kidney function and performed phase-contrast magnetic resonance imaging of basilar and carotid arteries to measure cerebral blood flow. Participants had an average (SD) eGFR of 86.3 (13.4) ml/min per 1.73 m(2) and a median (interquartile range) albumin-to-creatinine ratio of 3.4 (2.2-6.1) mg/g. In age- and sex-adjusted models, a higher albumin-to-creatinine ratio was associated with lower cerebral blood flow level (difference in cerebral blood flow [milliliters per minute per 100 ml] per doubling of the albumin-to-creatinine ratio, -0.31; 95% confidence interval, -0.58 to -0.03). The association was not present after adjustment for cardiovascular risk factors (P=0.10). Each 1 SD lower eGFR was associated with 0.42 ml/min per 100 ml lower cerebral blood flow (95% confidence interval, 0.01 to 0.83) adjusted for cardiovascular risk factors. Thus, in this population-based study, we observed that lower eGFR is independently associated with lower cerebral blood flow.

  17. Functional genetic targeting of embryonic kidney progenitor cells ex vivo.

    PubMed

    Junttila, Sanna; Saarela, Ulla; Halt, Kimmo; Manninen, Aki; Pärssinen, Heikki; Lecca, M Rita; Brändli, André W; Sims-Lucas, Sunder; Skovorodkin, Ilya; Vainio, Seppo J

    2015-05-01

    The embryonic mammalian metanephric mesenchyme (MM) is a unique tissue because it is competent to generate the nephrons in response to Wnt signaling. An ex vivo culture in which the MM is separated from the ureteric bud (UB), the natural inducer, can be used as a classic tubule induction model for studying nephrogenesis. However, technological restrictions currently prevent using this model to study the molecular genetic details before or during tubule induction. Using nephron segment-specific markers, we now show that tubule induction in the MM ex vivo also leads to the assembly of highly segmented nephrons. This induction capacity was reconstituted when MM tissue was dissociated into a cell suspension and then reaggregated (drMM) in the presence of human recombinant bone morphogenetic protein 7/human recombinant fibroblast growth factor 2 for 24 hours before induction. Growth factor-treated drMM also recovered the capacity for organogenesis when recombined with the UB. Cell tracking and time-lapse imaging of chimeric drMM cultures indicated that the nephron is not derived from a single progenitor cell. Furthermore, viral vector-mediated transduction of green fluorescent protein was much more efficient in dissociated MM cells than in intact mesenchyme, and the nephrogenic competence of transduced drMM progenitor cells was preserved. Moreover, drMM cells transduced with viral vectors mediating Lhx1 knockdown were excluded from the nephric tubules, whereas cells transduced with control vectors were incorporated. In summary, these techniques allow reproducible cellular and molecular examinations of the mechanisms behind nephrogenesis and kidney organogenesis in an ex vivo organ culture/organoid setting.

  18. Interactions between thyroid and kidney function in pathological conditions of these organ systems: a review.

    PubMed

    van Hoek, Ingrid; Daminet, Sylvie

    2009-02-01

    Thyroidal status affects kidney function already in the embryonic stage. Thyroid hormones influence general tissue growth as well as tubular functions, electrolyte handling and neural input. Hyper- and hypo-functioning of the thyroid influences mature kidney function indirectly by affecting the cardiovascular system and the renal blood flow, and directly by affecting glomerular filtration, electrolyte pumps, the secretory and absorptive capacity of the tubuli, and the structure of the kidney. Hyperthyroidism accelerates several physiologic processes, a fact which is reflected in the decreased systemic vascular resistance, increased cardiac output (CO), increased renal blood flow (RBF), hypertrophic and hyperplastic tubuli, and increased glomerular filtration rate (GFR). Renal failure can progress due to glomerulosclerosis, proteinuria and oxidative stress. Hypothyroidism has a more negative influence on kidney function. Peripheral vascular resistance is increased with intrarenal vasoconstriction, and CO is decreased, causing decreased RBF. The influence on the different tubular functions is modest, although the transport capacity is below normal. The GFR is decreased up to 40% in hypothyroid humans. Despite the negative influences on glomerular and tubular kidney function, a hypothyroid state has been described as beneficial in kidney disease. Kidney disease is associated with decreased thyroid hormone concentrations caused by central effects and by changes in peripheral hormone metabolism and thyroid hormone binding proteins. Geriatric cats form an animal model of disease because both hyperthyroidism and chronic kidney disease (CKD) have high prevalence among them, and the link between thyroid and kidney affects the evaluation of clinical wellbeing and the possible treatment options.

  19. Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

    PubMed Central

    Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

    2009-01-01

    Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

  20. Rate of change in kidney function and the risk of death: the case for incorporating the rate of kidney function decline into the CKD staging system.

    PubMed

    Al-Aly, Ziyad; Cepeda, Oscar

    2011-01-01

    Chronic kidney disease (CKD) is associated with increased risk of death. A wave of recent studies used longitudinal data to examine the effect of the rate of decline of kidney function on the risk of death. The results from these studies show that there is an independent and graded association between the rate of kidney function decline and the risk of death. There is a need to incorporate the rate of decline in the definition of CKD. This redefinition of CKD will transform a static definition into a dynamic one that more accurately describes the disease state in an individual patient.

  1. Bone mineral density, adiposity, and cognitive functions

    PubMed Central

    Sohrabi, Hamid R.; Bates, Kristyn A.; Weinborn, Michael; Bucks, Romola S.; Rainey-Smith, Stephanie R.; Rodrigues, Mark A.; Bird, Sabine M.; Brown, Belinda M.; Beilby, John; Howard, Matthew; Criddle, Arthur; Wraith, Megan; Taddei, Kevin; Martins, Georgia; Paton, Athena; Shah, Tejal; Dhaliwal, Satvinder S.; Mehta, Pankaj D.; Foster, Jonathan K.; Martins, Ian J.; Lautenschlager, Nicola T.; Mastaglia, Francis; Laws, Simon M.; Martins, Ralph N.

    2015-01-01

    Cognitive decline and dementia due to Alzheimer's disease (AD) have been associated with genetic, lifestyle, and environmental factors. A number of potentially modifiable risk factors should be taken into account when preventive or ameliorative interventions targeting dementia and its preclinical stages are investigated. Bone mineral density (BMD) and body composition are two such potentially modifiable risk factors, and their association with cognitive decline was investigated in this study. 164 participants, aged 34–87 years old (62.78 ± 9.27), were recruited for this longitudinal study and underwent cognitive and clinical examinations at baseline and after 3 years. Blood samples were collected for apolipoprotein E (APOE) genotyping and dual energy x-ray absorptiometry (DXA) was conducted at the same day as cognitive assessment. Using hierarchical regression analysis, we found that BMD and lean body mass, as measured using DXA were significant predictors of episodic memory. Age, gender, APOE status, and premorbid IQ were controlled for. Specifically, the List A learning from California Verbal Learning Test was significantly associated with BMD and lean mass both at baseline and at follow up assessment. Our findings indicate that there is a significant association between BMD and lean body mass and episodic verbal learning. While the involvement of modifiable lifestyle factors in human cognitive function has been examined in different studies, there is a need for further research to understand the potential underlying mechanisms. PMID:25741279

  2. Controversies Surrounding High-Protein Diet Intake: Satiating Effect and Kidney and Bone Health12

    PubMed Central

    Cuenca-Sánchez, Marta; Navas-Carrillo, Diana; Orenes-Piñero, Esteban

    2015-01-01

    Long-term consumption of a high-protein diet could be linked with metabolic and clinical problems, such as loss of bone mass and renal dysfunction. However, although it is well accepted that a high-protein diet may be detrimental to individuals with existing kidney dysfunction, there is little evidence that high protein intake is dangerous for healthy individuals. High-protein meals and foods are thought to have a greater satiating effect than high-carbohydrate or high-fat meals. The effect of high-protein diets on the modulation of satiety involves multiple metabolic pathways. Protein intake induces complex signals, with peptide hormones being released from the gastrointestinal tract and blood amino acids and derived metabolites being released in the blood. Protein intake also stimulates metabolic hormones that communicate information about energy status to the brain. Long-term ingestion of high amounts of protein seems to decrease food intake, body weight, and body adiposity in many well-documented studies. The aim of this article is to provide an extensive overview of the efficacy of high protein consumption in weight loss and maintenance, as well as the potential consequences in human health of long-term intake. PMID:25979491

  3. Mechanisms of Donor-Specific Tolerance in Recipients of Haploidentical Combined Bone Marrow/Kidney Transplantation

    PubMed Central

    Andreola, G.; Chittenden, M.; Shaffer, J.; Cosimi, A.B.; Kawai, T.; Cotter, P.; LoCascio, S.A.; Morokata, T.; Dey, B.R.; Tolkoff-Rubin, N.T.; Preffer, F.; Bonnefoix, T.; Kattleman, K.; Spitzer, T.R.; Sachs, D.H.; Sykes, M.

    2011-01-01

    We recently reported long-term organ allograft survival without ongoing immunosuppression in 4 of 5 patients receiving combined kidney and bone marrow transplantation from haploidentical donors following non-myeloablative conditioning. In vitro assays up to 18 months revealed donor-specific unresponsiveness. We now demonstrate that T cell recovery is gradual and is characterized by memory-type cell predominance and an increased proportion of CD4+CD25+CD127−FOXP3+ Treg during the lymphopenic period. Complete donor-specific unresponsiveness in proliferative and cytotoxic assays, and in limiting dilution analyses of IL-2-producing and cytotoxic cells, developed and persisted for the 3-year follow-up in all patients, and extended to donor renal tubular epithelial cells. Assays in 2 of 4 patients were consistent with a role for a suppressive tolerance mechanism at 6 months to 1 year, but later (≥18 months) studies on all 4 patients provided no evidence for a suppressive mechanism. Our studies demonstrate, for the first time, long-term, systemic donor-specific unresponsiveness in patients with HLA-mismatched allograft tolerance. While regulatory cells may play an early role, long-term tolerance appears to be maintained by a deletion or anergy mechanism. PMID:21645255

  4. Controversies surrounding high-protein diet intake: satiating effect and kidney and bone health.

    PubMed

    Cuenca-Sánchez, Marta; Navas-Carrillo, Diana; Orenes-Piñero, Esteban

    2015-05-01

    Long-term consumption of a high-protein diet could be linked with metabolic and clinical problems, such as loss of bone mass and renal dysfunction. However, although it is well accepted that a high-protein diet may be detrimental to individuals with existing kidney dysfunction, there is little evidence that high protein intake is dangerous for healthy individuals. High-protein meals and foods are thought to have a greater satiating effect than high-carbohydrate or high-fat meals. The effect of high-protein diets on the modulation of satiety involves multiple metabolic pathways. Protein intake induces complex signals, with peptide hormones being released from the gastrointestinal tract and blood amino acids and derived metabolites being released in the blood. Protein intake also stimulates metabolic hormones that communicate information about energy status to the brain. Long-term ingestion of high amounts of protein seems to decrease food intake, body weight, and body adiposity in many well-documented studies. The aim of this article is to provide an extensive overview of the efficacy of high protein consumption in weight loss and maintenance, as well as the potential consequences in human health of long-term intake.

  5. NOTCHing the bone: insights into multi-functionality.

    PubMed

    Engin, Feyza; Lee, Brendan

    2010-02-01

    Evolutionarily conserved Notch signaling plays a critical role during embryonic and postnatal life. The importance of Notch signaling in the determination of cell fate, and the spatio-temporal regulation of proliferation, differentiation and apoptosis has been demonstrated in various different organ systems. However, how Notch signaling affects the bone development was unknown until now. The in vivo effects of Notch signaling in lineage commitment, bone formation and bone resorption were demonstrated in recent studies. In addition to regulation of osteoblastogenesis, osteoblast directed osteoclastogenesis by Notch signaling revealed a dimorphic effect for this signaling pathway providing another example of such in bone development. Moreover, identification of the cross talk between the hematopoietic stem cell niche and osteoblasts through Notch signaling also suggested another important role for Notch signaling, i.e., the coupling of cellular components of the bone microenvironment. The association between the gain and loss of function of Notch activity in bone pathology highlights Notch as a potentially novel therapeutic target for the treatment of metabolic bone disease and bone cancer. In this review, we will focus primarily on the regulation of bone cells, i.e., osteoblasts and osteoclasts by Notch signaling. We will also review the importance of Notch in specifying bone-hematopoietic stem cell niche interactions within the bone microenvironment. Finally, we will discuss potential clinical implications and future directions for this field. (c) 2009 Elsevier Inc. All rights reserved.

  6. Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease.

    PubMed

    Diwan, Vishal; Gobe, Glenda; Brown, Lindsay

    2014-01-01

    The development of chronic kidney disease (CKD) and associated cardiovascular disease involves free radical damage and inflammation. Addition of adenine to the diet induces inflammation followed by CKD and cardiovascular disease. NOD-like receptor protein-3 (NLRP-3) is pro-inflammatory in the kidney; glibenclamide inhibits production of NLRP-3. Male Wistar rats were fed either control rat food or adenine (0.25%) in this food for 16 weeks. Glibenclamide (10 mg/kg/day) was administered to two groups with and without adenine for the final 8 weeks. Kidney function (blood urea nitrogen/BUN, plasma creatinine/PCr, plasma uric acid, proteinuria), kidney structure (fibrosis, inflammation), cardiovascular parameters (blood pressure, left ventricular stiffness, vascular responses and echocardiography) and protein expression of markers for oxidative stress (HO-1), and inflammation (TNF-α, NLRP-3) were assessed. In adenine-fed rats, glibenclamide decreased BUN (controls: 6±0.6; adenine: 56.6±5.4; adenine+glibenclamide: 19.4±2.7 mmol/L), PCr (controls: 42±2.8; adenine: 268±23; adenine+glibenclamide: 81±10 μmol/L), proteinuria (controls: 150±7.4; adenine: 303±19; adenine+glibenclamide: 220±13 μmol/L) (all p<0.05). Glibenclamide decreased infiltration of chronic inflammatory cells, fibrosis, tubular damage and expression of HO-1, TNF-α and NLRP-3 in the kidney. Glibenclamide did not alter plasma uric acid concentrations (controls: 38±1; adenine: 63±4; adenine+glibenclamide: 69±14 μmol/L). Cardiovascular changes included decreased systolic blood pressure and improved vascular responses although cardiac fibrosis, left ventricular stiffness and hypertrophy were not reduced. Glibenclamide improved kidney structure and function in CKD and decreased some cardiovascular parameters. Inflammatory markers and cell populations were attenuated by glibenclamide in kidneys. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Spleno-renal artery transposition in a solitary functioning kidney for treatment-resistant hypertension and acute kidney injury.

    PubMed

    Somalanka, Subash; Harris, Fiona E; Chemla, Eric; Suckling, Rebecca Jo; Swift, Pauline A

    2017-08-16

    Renal Artery Stenosis (RAS) is an important cause of treatment-resistant hypertension. Uncontrolled hypertension with RAS can cause progressive chronic kidney disease (CKD) leading to end-stage kidney disease. Therapeutic revascularisation can be helpful in appropriate circumstances where pharmaceutical intervention has failed and significant renovascular disease contributes to resistant hypertension. We present an interesting case of a Caucasian male with peripheral vasculopathy, abdominal aortic aneurysm (AAA), single functioning kidney and ostial RAS caused by stent struts from an endovascular AAA stent graft. He had escalating medications requirement, with repeated failed attempts at percutaneous radiological intervention that led to an episode of contrast-induced acute kidney injury (AKI), before undergoing successful surgical revascularisation by a splenic artery transposition graft to the left renal artery that was performed to improve kidney function and the blood pressure. This report highlights the challenges faced with regard to the management of severe hypertension and progressive CKD. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Emerging role of autophagy in kidney function, diseases and aging

    PubMed Central

    Huber, Tobias B.; Edelstein, Charles L.; Hartleben, Björn; Inoki, Ken; Jiang, Man; Koya, Daisuke; Kume, Shinji; Lieberthal, Wilfred; Pallet, Nicolas; Quiroga, Alejandro; Ravichandran, Kameswaran; Susztak, Katalin; Yoshida, Sei; Dong, Zheng

    2012-01-01

    Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy. PMID:22692002

  9. Long-term evaluation of kidney function in live-related kidney donors.

    PubMed

    Mehta, Kalpana S; Swami, Rudramani; Pajai, Atim; Bhurke, Sandip; Shirkande, Abhishek; Jawle, Sunil

    2017-01-01

    The consequences of live kidney donation on the donor health with main emphasis on postdonation blood pressure (BP), proteinuria, kidney size, and glomerular filtration rate (GFR) were evaluated. Twenty-five donors with minimum of six months postdonation duration were included in the study. Donor age at nephrectomy, duration postnephrectomy, systolic and diastolic BP measurement pre-and post-donation, postdonation, blood urea nitrogen, serum creatinine and 24-h proteinuria, blood sugar, two-dimensional echocardiogram were recorded. Kidney sizes pre-and post-donation were noted. GFR was calculated by chronic kidney disease epidemiology collaboration and modification of diet in renal disease formula and measured by diethylene triamine pentaacetic acid renogram in all donors pre-and post-donation. Twenty-one (84%) were female, and four (16%) were male. The mean age at donation was 46.24 ± 9.62 (28-65) years. Median duration postdonor nephrectomy was 26 (minimum 7 and maximum 228) months. There was a mean rise of 6.24 mm Hg in systolic and 4.20 mm Hg diastolic BP (P = 0.001). Remnant kidney size increased from 35.12 ± 6.80 to 42.32 ± 8.59 sq cm (P <0.0001). There was reduction of postdonation GFR from 94.50 ± 18.12 mL/min to 60.48 ± 14.32 mL/min after nephrectomy (P <0.0001). There was significant increase in remnant kidney GFR from 48.83 ± 7.79 mL/min to 60.48 ± 14.32 mL/min (P <0.0001). Two donors had hypertension postdonation while 23 did not. No donor developed postdonation proteinuria. A significant increase in the kidney size and GFR was evident in remnant native kidney in all. No mortality was observed.

  10. A Lifetime of Allograft Function with Kidneys from Older Donors.

    PubMed

    Rose, Caren; Schaeffner, Elke; Frei, Ulrich; Gill, Jagbir; Gill, John S

    2015-10-01

    Strategies to increase expanded criteria donor (ECD) transplantation are needed. We quantified the extent to which ECD kidneys provide recipients with a lifetime of allograft function by determining the difference between patient survival and death-censored allograft survival (graft survival). Initial analyses compared 5-year outcomes in the Eurotransplant Senior Program (European) and the United States Renal Data System. Among European recipients ≥65 years, patient survival exceeded graft survival, and ECD recipients returned to dialysis for an average of 5.2 months after transplant failure. Among United States recipients ≥60 years, graft survival exceeded patient survival. Although patient survival in elderly recipients in the United States was low (49% at 5 years), the average difference in patient survival at 10 years in elderly recipients in the United States with an ECD versus non-ECD transplant was only 7 months. The probability of patient survival with a functioning allograft at 5 years was higher with ECD transplantation within 1 year after activation to the waiting list than with delayed non-ECD transplantation ≥3 years after activation to the waiting list. Subsequent analyses demonstrated that ECD transplants do not provide a lifetime of allograft function in recipients <50 years in the United States. These findings should encourage ECD transplantation in patients ≥60 years, demonstrate that rapid ECD transplantation is superior to delayed non-ECD transplantation, and challenge the policy in the United States of allowing patients <50 years to receive an ECD transplant.

  11. The anomalies associated with congenital solitary functioning kidney in children.

    PubMed

    Akl, Kamal

    2011-01-01

    The aim of this study was to determine the incidence of associated urological and non-urological anomalies as well as the renal outcome in patients with a congenital solitary func-tioning kidney (CSFK). A retrospective review of 30 consecutive cases of CSFK seen at the pediatric renal service at the Jordan University Hospital between 2004 and 2008 was performed. There were 20 males and 10 females, whose ages ranged from five days to 14 years. In 20 patients (67%), the left kidney was absent. Associated anomalies were detected in 23 (77%) of the 30 patients; urological anomalies accounted for 47% (14/30) and non-urological anomalies were found in 19/30 (53%) patients. The latter included anomalies of the ear, nose and throat (ENT) in 9/30 (30%), musculoskeletal system (one with hypermobile joints) in 8/30 (27%), gastrointestinal (GI) in 7/30 (23%), cardiovascular (CV) in 4/30 (13%) and dermatological with epidermolysis bullosa, endocrine (euthyroid goiter) and gynecological (cervical cyst) in one patient each (3%). Proteinuria was seen in 6/30 (20%) and hypertension in 2/30 (7%) patients. Chronic renal failure (CRF) was seen in 6/30 (20%) patients, of whom three had end-stage renal failure (ESRF). CRF was seen mainly in patients with more than two associated urological anomalies. Idiopathic hyperuricosuria was found in five of the six tested patients (83%). In our study, the most common associated anomalies with CSFK were urological. The presence of more than two associated urological anomalies increased the risk of CRF.

  12. Associations of TNFR1 with kidney function outcomes by age, gender, and baseline kidney function status: Data from the Heart and Soul Study.

    PubMed

    Park, Meyeon; Maristany, Daniela; Huang, Debbie; Shlipak, Michael G; Whooley, Mary

    2017-10-01

    Tumor necrosis factor receptor type 1 (TNFR1) is associated with kidney disease and mortality risk in various populations [1], [2]. We evaluated associations of TNFR1 with mortality and mediators of this relationship in doi: 10.1016/j.atherosclerosis.2017.05.021. Whether or not these associations are influenced by age, gender, or baseline kidney function are not known. We evaluated associations of TNFR1 levels with measures of kidney function stratifying by these variables. Our outcomes included estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2), albumin to creatinine ratio (ACR) >30 mg/g, and rapid kidney function loss, defined as a change in eGFR of greater than 3% per year.

  13. Delayed Graft Function Phenotypes and 12-Month Kidney Transplant Outcomes.

    PubMed

    Hall, Isaac E; Reese, Peter P; Doshi, Mona D; Weng, Francis L; Schröppel, Bernd; Asch, William S; Ficek, Joseph; Thiessen-Philbrook, Heather; Parikh, Chirag R

    2017-08-01

    Ischemia-reperfusion injury (IRI) leading to delayed graft function (DGF), defined by the United Network for Organ Sharing as dialysis in the first week (UNOS-DGF), associates with poor kidney transplant outcomes. Controversies remain, however, about dialysis initiation thresholds and the utility for other criteria to denote less severe IRI, or slow graft function (SGF). Multicenter, prospective study of deceased-donor kidney recipients to compare UNOS-DGF to a definition that combines impaired creatinine reduction in the first 48 hours or greater than 1 dialysis session for predicting 12-month estimated glomerular filtration rate (eGFR). We also assessed 10 creatinine and urine output-based SGF definitions relative to 12-month eGFR. In 560 recipients, 215 (38%) had UNOS-DGF, 330 (59%) met the combined definition, 14 (3%) died, and 23 (4%) had death-censored graft failure by 12 months. Both DGF definitions were associated with lower adjusted 12-month eGFR (95% confidence interval)-by 7.3 (3.6-10.9) and 7.4 (3.8-11.0) mL/min per 1.73 m, respectively. Adjusted relative risks for 12-month eGFR less than 30 mL/min per 1.73 m were 1.9 (1.2-3.1) and 2.1 (1.1-3.7), with unadjusted areas under the curve of 0.618 and 0.627, respectively. For SGF definitions, postoperative day (POD) 7 creatinine had the strongest association with 12-month eGFR, and POD5 creatinine and creatinine reduction between POD1 and POD2 demonstrated modest separations in 12-month eGFR. Although UNOS-DGF does not adequately predict 12-month function on its own, our findings do not support changing the definition. Postoperative day 7 creatinine is correlated with 12-month eGFR, but large translational studies are needed to understand the biological link between IRI severity at transplant and longer-term outcomes.

  14. Cystatin-C is associated with partial recovery of kidney function and progression to chronic kidney disease in living kidney donors: Observational study.

    PubMed

    Bang, Ji-Yeon; Kim, Seon-Ok; Kim, Sae-Gyul; Song, Jun-Gol; Hwang, Gyu Sam

    2017-02-01

    Donor nephrectomy in living-donor kidney transplantation may result in hyperfiltration injury in remnant kidney; however, its clinical implication in partial recovery of kidney function (PRKF) in remnant kidney and chronic kidney disease (CKD) progression remains unclear. Thus, we investigated the effect of PRKF on CKD development in the residual kidney and the utility of cystatin-C (Cys-C) in evaluating renal function in living-donor kidney transplantation donors.The electronic medical records and laboratory results of 1648 kidney transplant (KT) donors and 13,834 healthy nondonors between January 2006 and November 2014 were reviewed. The predictors of PRKF and CKD diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria were evaluated by multivariate analysis. CKD risk was compared between KT donors and healthy nondonors using Cox proportional hazard regression analysis following propensity score matching (PSM).The incidence of PRKF for KT donors was 49.3% (813). CKD incidence was 24.8% (408) in KT donors and 2.0% (277) in healthy nondonors. The predictors of PRKF were, male sex (odds ratio [OR], 17.32; 95% confidence interval [CI] 9.16-32.77), age (OR, 1.02; 95% CI, 1.00-1.04; P < 0.001), Cys-C concentration (OR, 1.02; 95% CI, 1.00-1.04; P = 0.02), and preoperative albumin level (OR, 0.49; 95% CI, 0.27-0.89; P = 0.02). The predictors of CKD were age (hazards ratio [HR], 1.04; 95% CI, 1.02-1.05; P < 0.001), Cys-C concentration (HR, 1.024; 95% CI, 1.012-1.037; P < 0.001), and PRKF (HR, 1.41; 95% CI, 1.04-1.92; P = 0.03). After PSM, the risk of progression to CKD was higher in KT donors than in healthy nondonors (HR, 58.4; 95% CI, 34.2-99.8; P < 0.001).Donor nephrectomy is associated with PRKF and progression to CKD. Cys-C is a useful early marker for detecting PRKF and CKD.

  15. Cystatin-C is associated with partial recovery of kidney function and progression to chronic kidney disease in living kidney donors

    PubMed Central

    Bang, Ji-Yeon; Kim, Seon-Ok; Kim, Sae-Gyul; Song, Jun-Gol; Hwang, Gyu Sam

    2017-01-01

    Abstract Donor nephrectomy in living-donor kidney transplantation may result in hyperfiltration injury in remnant kidney; however, its clinical implication in partial recovery of kidney function (PRKF) in remnant kidney and chronic kidney disease (CKD) progression remains unclear. Thus, we investigated the effect of PRKF on CKD development in the residual kidney and the utility of cystatin-C (Cys-C) in evaluating renal function in living-donor kidney transplantation donors. The electronic medical records and laboratory results of 1648 kidney transplant (KT) donors and 13,834 healthy nondonors between January 2006 and November 2014 were reviewed. The predictors of PRKF and CKD diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria were evaluated by multivariate analysis. CKD risk was compared between KT donors and healthy nondonors using Cox proportional hazard regression analysis following propensity score matching (PSM). The incidence of PRKF for KT donors was 49.3% (813). CKD incidence was 24.8% (408) in KT donors and 2.0% (277) in healthy nondonors. The predictors of PRKF were, male sex (odds ratio [OR], 17.32; 95% confidence interval [CI] 9.16–32.77), age (OR, 1.02; 95% CI, 1.00–1.04; P < 0.001), Cys-C concentration (OR, 1.02; 95% CI, 1.00–1.04; P = 0.02), and preoperative albumin level (OR, 0.49; 95% CI, 0.27–0.89; P = 0.02). The predictors of CKD were age (hazards ratio [HR], 1.04; 95% CI, 1.02–1.05; P < 0.001), Cys-C concentration (HR, 1.024; 95% CI, 1.012–1.037; P < 0.001), and PRKF (HR, 1.41; 95% CI, 1.04–1.92; P = 0.03). After PSM, the risk of progression to CKD was higher in KT donors than in healthy nondonors (HR, 58.4; 95% CI, 34.2–99.8; P < 0.001). Donor nephrectomy is associated with PRKF and progression to CKD. Cys-C is a useful early marker for detecting PRKF and CKD. PMID:28151912

  16. The Association between Elevated Levels of Peripheral Serotonin and Its Metabolite – 5-Hydroxyindoleacetic Acid and Bone Strength and Metabolism in Growing Rats with Mild Experimental Chronic Kidney Disease

    PubMed Central

    Oksztulska-Kolanek, Ewa; Znorko, Beata; Domaniewski, Tomasz; Rogalska, Joanna; Roszczenko, Alicja; Brzóska, Małgorzata Michalina; Pryczynicz, Anna; Kemona, Andrzej

    2016-01-01

    Chronic kidney disease (CKD) is associated with disturbances in bone strength and metabolism. The alterations of the serotonergic system are also observed in CKD. We used the 5/6 nephrectomy model of CKD to assess the impact of peripheral serotonin and its metabolite– 5-hydroxyindoleacetic acid on bone biomechanical properties and metabolism in growing rats. The animals were sacrificed one and three months after nephrectomy. Biomechanical properties were determined on two different bone types: the cortical bone of the femoral diaphysis using three-point bending test and the mixed cortico-trabecular bone by the bending test of the femoral neck. Biomechanical tests revealed preserved cortical bone strength, whereas work to fracture (W) and yield load (Fy) of mixed cortico-trabecular bone were significantly lower in CKD compared to controls. Serum activity of alkaline phosphatase (ALP), a bone formation marker, and tartrate-resistant acid phosphatase (TRACP 5b) reflecting bone resorption, were similar in CKD and controls. ALP was associated with lower femoral stiffness and strength, and higher displacements and W. TRACP 5b was inversely associated with cortical Fu and W. The elevated peripheral serotonergic system in CKD was: inversely associated with stiffness but positively related to the displacements and W; inversely associated with cortical Fy but positively correlated with this parameter in cortico-trabecular bone; inversely associated with ALP in controls but positively correlated with this biomarker in CKD animals. In conclusion, this study demonstrates the distinct effect of mild degree of CKD on bone strength in rapidly growing rats. The impaired renal function affects the peripheral serotonin metabolism, which in turn may influence the strength and metabolism of bones in these rats. This relationship seems to be beneficial on the biomechanical properties of the cortico-trabecular bone, whereas the cortical bone strength can be potentially reduced. PMID

  17. Measuring dynamic kidney function in an undergraduate physiology laboratory.

    PubMed

    Medler, Scott; Harrington, Frederick

    2013-12-01

    Most undergraduate physiology laboratories are very limited in how they treat renal physiology. It is common to find teaching laboratories equipped with the capability for high-resolution digital recordings of physiological functions (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most urinary laboratories still rely on a "dipstick" approach of urinalysis. Although this technique can provide some basic insights into the functioning of the kidneys, it overlooks the dynamic processes of filtration, reabsorption, and secretion. In the present article, we provide a straightforward approach of using renal clearance measurements to estimate glomerular filtration rate, fractional water reabsorption, glucose clearance, and other physiologically relevant parameters. The estimated values from our measurements in laboratory are in close agreement with those anticipated based on textbook parameters. For example, we found glomerular filtration rate to average 124 ± 45 ml/min, serum creatinine to be 1.23 ± 0.4 mg/dl, and fractional water reabsorption to be ∼96.8%. Furthermore, analyses for the class data revealed significant correlations between parameters like fractional water reabsorption and urine concentration, providing opportunities to discuss urine concentrating mechanisms and other physiological processes. The procedures outlined here are general enough that most undergraduate physiology laboratory courses should be able to implement them without difficulty.

  18. Functional and morphologic damage in the neonatally irradiated canine kidney

    SciTech Connect

    Peneyra, R.S.; Jaenke, R.S.

    1985-11-01

    Perinatal irradiation of the developing kidney results in progressive glomerulosclerosis (PGS) and renal failure. This syndrome may result from direct radiation damage to mature deep cortical nephrons and/or nephron functional adaptations resulting from outer cortical nephron ablation. Beagle dogs received single, whole-body exposures (330 R) to /sup 60/Co gamma radiation at 4 days of age (IR4) to study the combined effects of direct radiation damage and nephron loss, or at 30 days of age (IR30) to study the effects of renal irradiation alone. To study the effects of nephron loss alone, dogs underwent unilateral nephrectomy (UN4) or superficial hyperthermic renal ablation (HY4) at 4 days of age. Nephron loss due to irradiation (IR4) and partial renal ablation (UN4 and HY4) was associated with compensatory nephron hypertrophy and increased single nephron glomerular filtration rate (SNGFR), while irradiation at 30 days resulted in transitory decreased SNGFR. Similar degrees of PGS occurred in IR4 dogs which experienced both irradiation and loss of nephrons and UN4 and HY4 dogs which experienced only loss of nephrons. PGS of lesser severity also occurred in IR30 dogs. These findings indicate that PGS associated with perinatal renal irradiation results from direct radiation damage to deep cortical nephrons and compensatory functional changes occurring in response to loss of renal mass.

  19. Estimating residual kidney function in dialysis patients without urine collection.

    PubMed

    Shafi, Tariq; Michels, Wieneke M; Levey, Andrew S; Inker, Lesley A; Dekker, Friedo W; Krediet, Raymond T; Hoekstra, Tiny; Schwartz, George J; Eckfeldt, John H; Coresh, Josef

    2016-05-01

    Residual kidney function contributes substantially to solute clearance in dialysis patients but cannot be assessed without urine collection. We used serum filtration markers to develop dialysis-specific equations to estimate urinary urea clearance without the need for urine collection. In our development cohort, we measured 24-hour urine clearances under close supervision in 44 patients and validated these equations in 826 patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. For the development and validation cohorts, median urinary urea clearance was 2.6 and 2.4 ml/min, respectively. During the 24-hour visit in the development cohort, serum β-trace protein concentrations remained in steady state but concentrations of all other markers increased. In the validation cohort, bias (median measured minus estimated clearance) was low for all equations. Precision was significantly better for β-trace protein and β2-microglobulin equations and the accuracy was significantly greater for β-trace protein, β2-microglobulin, and cystatin C equations, compared with the urea plus creatinine equation. Area under the receiver operator characteristic curve for detecting measured urinary urea clearance by equation-estimated urinary urea clearance (both 2 ml/min or more) were 0.821, 0.850, and 0.796 for β-trace protein, β2-microglobulin, and cystatin C equations, respectively; significantly greater than the 0.663 for the urea plus creatinine equation. Thus, residual renal function can be estimated in dialysis patients without urine collections.

  20. Age, kidney function, and risk factors associate differently with cortical and medullary volumes of the kidney

    PubMed Central

    Wang, Xiangling; Vrtiska, Terri J.; Avula, Ramesh T.; Walters, Leah R.; Chakkera, Harini A.; Kremers, Walter K.; Lerman, Lilach O.; Rule, Andrew D.

    2013-01-01

    The kidney atrophies in patients with advanced chronic kidney disease (CKD) but factors influencing kidney size in normal adults are less clear. To help define this we measured kidney volumes on contrast-enhanced CT images from 1344 potential kidney donors (ages 18 to 75 years). Cortical volume per body surface area progressively declined in both genders with increased age. Statistically, this was primarily dependent on the age-related decline in glomerular filtration rate (GFR). Independent predictors of increased cortical volume per body surface area were male gender, increased GFR, increased 24-hour urine albumin, current smoker, and decreased high-density lipid cholesterol. Medullary volume per body surface area increased with age in men while it increased with age in women until age 50 followed by a subsequent decline. Independent predictors of increased medullary volume per body surface area were older age, male gender, increased GFR, increased 24-hour urine albumin, increased serum glucose, and decreased serum uric acid. Thus, while cortical volume declines with age along the same biological pathway as the age-related decline in GFR and albuminuria some CKD risk factors are actually associated with increased cortical or medullary volume among relatively healthy adults. Underlying hypertrophy or atrophy of different nephron regions may explain these findings. PMID:24067437

  1. Unilateral nephrectomy 24 hours after bilateral kidney irradiation reduces damage to the function and structure of the remaining kidney

    SciTech Connect

    Liao, Z.X.; Travis, E.L.

    1994-09-01

    The effect of unilateral nephrectomy 24 h after irradiation on renal function and death with renal insufficiency as well as histopathological changes in the kidney was assessed. Single doses totaling 8-18 Gy were given bilaterally to unanesthetized female and male C3Hf/Kam mice. Renal function damage was assayed by blood urea nitrogen (BUN) and hematocrit (Hct). Histological damage was quantified by two parameters: kidney area and number of surviving tubule cells along the renal capsule. The number of glomeruli was scored as an indication of the number of nephrons. Changes in the two functional parameters did not appear sooner after irradiation in the nephrectomized mice than in the non-nephrectomized mice. Rather, less impairment of function was measured by both parameters in the nephrectomized mice but only after radiation doses greater than 12 Gy. The LD{sub 50} at 424 days after irradiation was also higher in the nephrectomized mice than in the mice receiving only irradiation, 13.98 Gy (95% confidence limits = 12.03, 15.93) and 11.71 Gy (95% confidence limits = 10.4, 13.1), respectively, in agreement with the data on function. Unilateral nephrectomy alone induced a 10% increase in size of the contralateral kidney. The dose-response curve for the kidney area from nephrectomized mice was parallel to and displaced above that for non-nephrectomized mice, indicating that the increase in renal mass occurred independent of and was not compromised by radiation. Unilateral nephrectomy alone induced no increase in the number of proximal tubules in the contralateral kidney. 30 refs., 9 figs., 1 tab.

  2. 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.

  3. 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.

  4. Function of osteocytes in bone--their role in mechanotransduction.

    PubMed

    Burger, E H; Klein-Nulend, J; van der Plas, A; Nijweide, P J

    1995-07-01

    Although osteocytes are by far the most abundant cell type of bone, they are least understood in terms of function and regulation. Previous studies have concentrated on their possible role as mobilizers of bone calcium, via the process of osteocytic osteolysis. Currently, however, their possible involvement in mechanical adaptation, the process whereby bone tissue maintains maximal functional strength with minimal bone mass, is discussed. We have recently obtained experimental evidence that osteocytes are the mechanosensory cells of bone, involved in the transduction of mechanical loads into biochemical signals. Our results support the hypothesis that flow of fluid through the lacunar-canalicular system as a result of loading provides the physical signal that activates the cells.

  5. 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.

  6. Identification of differentially expressed miRNAs associated with chronic kidney disease-mineral bone disorder.

    PubMed

    Kim, Kyung Im; Jeong, Sohyun; Han, Nayoung; Oh, Jung Mi; Oh, Kook-Hwan; Kim, In-Wha

    2017-09-01

    The purpose of this study is to characterize a meta-signature of differentially expressed mRNA in chronic kidney disease (CKD) to predict putative microRNA (miRNA) in CKD-mineral bone disorder (CKD-MBD) and confirm the changes in these genes and miRNA expression under uremic conditions by using a cell culture system. PubMed searches using MeSH terms and keywords related to CKD, uremia, and mRNA arrays were conducted. Through a computational analysis, a meta-signature that characterizes the significant intersection of differentially expressed mRNA and expected miRNAs associated with CKD-MBD was determined. Additionally, changes in gene and miRNA expressions under uremic conditions were confirmed with human Saos-2 osteoblast-like cells. A statistically significant mRNA meta-signature of upregulated and downregulated mRNA levels was identified. Furthermore, miRNA expression profiles were inferred, and computational analyses were performed with the imputed microRNA regulation based on weighted ranked expression and putative microRNA targets (IMRE) method to identify miRNAs associated with CKD occurrence. TLR4 and miR-146b levels were significantly associated with CKD-MBD. TLR4 levels were significantly downregulated, whereas primiR- 146b and miR-146b were upregulated in the presence of uremic toxins in human Saos-2 osteoblast-like cells. Differentially expressed miRNAs associated with CKD-MBD were identified through a computational analysis, and changes in gene and miRNA expressions were confirmed with an in vitro cell culture system.

  7. Modeling transport in the kidney: investigating function and dysfunction

    PubMed Central

    2010-01-01

    Mathematical models of water and solute transport in the kidney have significantly expanded our understanding of renal function in both health and disease. This review describes recent theoretical developments and emphasizes the relevance of model findings to major unresolved questions and controversies. These include the fundamental processes by which urine is concentrated in the inner medulla, the ultrastructural basis of proteinuria, irregular flow oscillation patterns in spontaneously hypertensive rats, and the mechanisms underlying the hypotensive effects of thiazides. Macroscopic models of water, NaCl, and urea transport in populations of nephrons have served to test, confirm, or refute a number of hypotheses related to the urine concentrating mechanism. Other macroscopic models focus on the mechanisms, role, and irregularities of renal hemodynamic control and on the regulation of renal oxygenation. At the mesoscale, models of glomerular filtration have yielded significant insight into the ultrastructural basis underlying a number of disorders. At the cellular scale, models of epithelial solute transport and pericyte Ca2+ signaling are being used to elucidate transport pathways and the effects of hormones and drugs. Areas where further theoretical progress is conditional on experimental advances are also identified. PMID:19889951

  8. Nephron hypertrophy and glomerulosclerosis and their association with kidney function and risk factors among living kidney donors.

    PubMed

    Elsherbiny, Hisham E; Alexander, Mariam P; Kremers, Walter K; Park, Walter D; Poggio, Emilio D; Prieto, Mikel; Lieske, John C; Rule, Andrew D

    2014-11-07

    The relationship of kidney function and CKD risk factors to structural changes in the renal parenchyma of normal adults is unclear. This study assessed whether nephron hypertrophy and nephrosclerosis had similar or different associations with kidney function and risk factors. From 1999 to 2009, 1395 living kidney donors had a core needle biopsy of their donated kidney during transplant surgery. The mean nonsclerotic glomerular volume and glomerular density (globally sclerotic and nonsclerotic) were estimated using the Weibel and Gomez stereologic methods. All tubules were counted in 1 cm(2) of cortex to determine a mean profile tubular area. Nephron hypertrophy was identified by larger glomerular volume, larger profile tubular area, and lower nonsclerotic glomerular density. Nephrosclerosis was identified by higher globally sclerotic glomerular density. The mean (± SD) age was 44 ± 12 years, 24-hour urine albumin excretion was 5 ± 7 mg, measured GFR was 103 ± 17 ml/min per 1.73 m(2), uric acid was 5.2 ± 1.4 mg/dl, and body mass index was 28 ± 5 kg/m(2). Of the study participants, 43% were men, 11% had hypertension, and 52% had a family history of ESRD. Larger glomerular volume, larger profile tubular area, and lower nonsclerotic glomerular density were correlated. Male sex, higher 24-hour urine albumin excretion, family history of ESRD, and higher body mass index were independently associated with each of these measures of nephron hypertrophy. Higher uric acid, higher GFR, and older age were also independently associated with some of these measures of nephron hypertrophy. Hypertension was not independently associated with measures of nephron hypertrophy. However, hypertension and older age were independently associated with higher globally sclerotic glomerular density. Nephron hypertrophy and nephrosclerosis are structural characteristics in normal adults that relate differently to clinical characteristics and may reflect kidney function and risk factors via

  9. Rapamycin reduces kidney volume and delays the loss of renal function in a patient with autosomal-dominant polycystic kidney disease

    PubMed Central

    Peces, Ramón; Peces, Carlos; Pérez-Dueñas, Virginia; Cuesta-López, Emilio; Azorín, Sebastián; Selgas, Rafael

    2009-01-01

    This is the first report of a case of a reduction in kidney volume and preservation of renal function in a patient with autosomal-dominant polycystic kidney disease (ADPKD) receiving rapamycin. A 42-year-old man with ADPKD and a severe persistent bleeding from his solitary left kidney was successfully treated with tranexamic acid (TXA). He also received low-dose rapamycin for 8 months, and this was associated with a 23.5% reduction in kidney volume, improvement and stabilization of renal function, and normalization of haemoglobin levels. When treatment with rapamycin was interrupted, renal function deteriorated within an 8-month period and haemodialysis (HD) became necessary. Kidney volume increased at once, and life-threatening bleeding prompted a nephrectomy 4 months after the onset of HD. These data suggest that the reduction in kidney volume and preservation of renal function with rapamycin could be the result of the antiangiogenic, antiproliferative effects of rapamycin. PMID:25949309

  10. Rapamycin reduces kidney volume and delays the loss of renal function in a patient with autosomal-dominant polycystic kidney disease.

    PubMed

    Peces, Ramón; Peces, Carlos; Pérez-Dueñas, Virginia; Cuesta-López, Emilio; Azorín, Sebastián; Selgas, Rafael

    2009-04-01

    This is the first report of a case of a reduction in kidney volume and preservation of renal function in a patient with autosomal-dominant polycystic kidney disease (ADPKD) receiving rapamycin. A 42-year-old man with ADPKD and a severe persistent bleeding from his solitary left kidney was successfully treated with tranexamic acid (TXA). He also received low-dose rapamycin for 8 months, and this was associated with a 23.5% reduction in kidney volume, improvement and stabilization of renal function, and normalization of haemoglobin levels. When treatment with rapamycin was interrupted, renal function deteriorated within an 8-month period and haemodialysis (HD) became necessary. Kidney volume increased at once, and life-threatening bleeding prompted a nephrectomy 4 months after the onset of HD. These data suggest that the reduction in kidney volume and preservation of renal function with rapamycin could be the result of the antiangiogenic, antiproliferative effects of rapamycin.

  11. Renal function in congenital anomalies of the kidney and urinary tract.

    PubMed

    Kemper, M J; Müller-Wiefel, D E

    2001-11-01

    Congenital anomalies of the kidneys and urinary tract are a major cause of chronic and end-stage renal failure in children. The molecular mechanisms having been elaborated, there is now growing evidence that kidney function is to a large extent determined genetically at an early stage. Assessment of kidney function is an important tool in clinical medicine and is feasible in utero. Postnatally, determination of absolute glomerular filtration rate and also of split and excretory renal function play an important role in the determination of treatment and prognosis. This is supplemented by other biochemical, molecular and interventional prognostic factors, which are of help in preservation of kidney survival by minimizing modulating factors. If chronic or terminal renal failure ensues in childhood or even in early infancy, however, improved medical care has led to encouraging results, ultimately influencing the motivation in the care of children with congenital anomalies of the kidney and urinary tract.

  12. 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

  13. 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

  14. 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

  15. Short-term Effects of Tolvaptan in Individuals With Autosomal Dominant Polycystic Kidney Disease at Various Levels of Kidney Function.

    PubMed

    Boertien, Wendy E; Meijer, Esther; de Jong, Paul E; ter Horst, Gert J; Renken, Remco J; van der Jagt, Eric J; Kappert, Peter; Ouyang, John; Engels, Gerwin E; van Oeveren, Willem; Struck, Joachim; Czerwiec, Frank S; Oberdhan, Dorothee; Krasa, Holly B; Gansevoort, Ron T

    2015-06-01

    A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance≥60mL/min. The aim of our study was to determine whether the renal hemodynamic effects and pharmacodynamic efficacy of tolvaptan in ADPKD are dependent on GFR. Clinical trial with comparisons before and after treatment. Patients with ADPKD with a wide range of measured GFRs (mGFRs; 18-148 mL/min) in a hospital setting. Participants were studied at baseline and after 3 weeks of treatment with tolvaptan given in increasing dosages, if tolerated (doses of 60, 90, and 120mg/d in weeks 1, 2, and 3, respectively). Change in markers for aquaresis (free-water clearance, urine and plasma osmolality, 24-hour urine volume, and plasma copeptin) and kidney injury (TKV and kidney injury biomarkers). GFR was measured by (125)I-iothalamate clearance; TKV, by magnetic resonance imaging; biomarker excretion, by enzyme-linked immunosorbent assay; and osmolality, by freezing point depression. In 27 participants (52% men; aged 46±10 years; mGFR, 69±39mL/min; TKV, 2.15 [IQR, 1.10-2.77] L), treatment with tolvaptan led to an increase in urine volume and free-water clearance and a decrease in urine osmolality, TKV, and kidney injury marker excretion. Changes in urine volume and osmolality with treatment were less in participants with lower baseline mGFRs (both P<0.01). However, change in fractional free-water clearance was greater at lower baseline mGFRs (P=0.001), suggesting that participants with decreased GFRs responded more to tolvaptan per functioning nephron. Limited sample size, no control group. In patients with ADPKD with decreased kidney function, response to tolvaptan is lower for TKV, urinary volume, and osmolality, but larger for fractional free-water clearance. This latter finding suggests that patients with ADPKD with

  16. 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.

  17. Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States.

    PubMed

    Huang, Yihung; Tilea, Anca; Gillespie, Brenda; Shahinian, Vahakn; Banerjee, Tanushree; Grubbs, Vanessa; Powe, Neil; Rios-Burrows, Nilka; Pavkov, Meda; Saran, Rajiv

    2017-03-07

    Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m(2) and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m(2) among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.

  18. Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation.

    PubMed

    Ting, Stephen M S; Iqbal, Hasan; Kanji, Hemali; Hamborg, Thomas; Aldridge, Nicolas; Krishnan, Nithya; Imray, Chris H E; Banerjee, Prithwish; Bland, Rosemary; Higgins, Robert; Zehnder, Daniel

    2014-01-01

    Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for ≤5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT <40% of predicted peak VO2 had a significantly reduced 5-year cumulative overall survival rate compared with those with AT ≥40% (P<0.001). Regarding the cohort with AT <40%, patients who underwent kidney transplantation (6 deaths) had significantly better survival compared with nontransplanted patients (17 deaths) (hazard ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT ≥40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

  19. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2015-12-01

    Award Number: W81XWH-12-1-0377 TITLE: The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation PRINCIPAL...Sep 2015 4. TITLE AND SUBTITLE The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in 5a. CONTRACT NUMBER PR110178 Bone...adapt to mechanical loading (exercise). Degeneration in peripheral nerve function with age may be one of these mechanisms, as neuropeptides affect

  20. Residual Kidney Function Decline and Mortality in Incident Hemodialysis Patients.

    PubMed

    Obi, Yoshitsugu; Rhee, Connie M; Mathew, Anna T; Shah, Gaurang; Streja, Elani; Brunelli, Steven M; Kovesdy, Csaba P; Mehrotra, Rajnish; Kalantar-Zadeh, Kamyar

    2016-12-01

    In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9-5.0) and -1.1±2.8 ml/min per 1.73 m(2), respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of -6.0 and +3.0 ml/min per 1.73 m(2) per year associated with case mix-adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: -1.5 ml/min per 1.73 m(2) per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined. Copyright © 2016 by the American Society of Nephrology.

  1. Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation.

    PubMed

    Kaths, J Moritz; Echeverri, Juan; Chun, Yi Min; Cen, Jun Yu; Goldaracena, Nicolas; Linares, Ivan; Dingwell, Luke S; Yip, Paul M; John, Rohan; Bagli, Darius; Mucsi, Istvan; Ghanekar, Anand; Grant, David R; Robinson, Lisa A; Selzner, Markus

    2017-04-01

    Donation after circulatory death (DCD) is current clinical practice to increase the donor pool. Deleterious effects on renal graft function are described for hypothermic preservation. Therefore, current research focuses on investigating alternative preservation techniques, such as normothermic perfusion. We compared continuous pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) with static cold storage (SCS) in a porcine model of DCD autotransplantation. After 30 minutes of warm ischemia, right kidneys were removed from 30-kg Yorkshire pigs and preserved with 8-hour NEVKP or in 4°C histidine-tryptophan-ketoglutarate solution (SCS), followed by kidney autotransplantation. Throughout NEVKP, electrolytes and pH values were maintained. Intrarenal resistance decreased over the course of perfusion (0 hour, 1.6 ± 0.51 mm per minute vs 7 hours, 0.34 ± 0.05 mm Hg/mL per minute, P = 0.005). Perfusate lactate concentration also decreased (0 hour, 10.5 ± 0.8 vs 7 hours, 1.4 ± 0.3 mmol/L, P < 0.001). Cellular injury markers lactate dehydrogenase and aspartate aminotransferase were persistently low (lactate dehydrogenase < 100 U/L, below analyzer range; aspartate aminotransferase 0 hour, 15.6 ± 9.3 U/L vs 7 hours, 24.8 ± 14.6 U/L, P = 0.298). After autotransplantation, renal grafts preserved with NEVKP demonstrated lower serum creatinine on days 1 to 7 (P < 0.05) and lower peak values (NEVKP, 5.5 ± 1.7 mg/dL vs SCS, 11.1 ± 2.1 mg/dL, P = 0.002). The creatinine clearance on day 4 was increased in NEVKP-preserved kidneys (NEVKP, 39 ± 6.4 vs SCS, 18 ± 10.6 mL/min; P = 0.012). Serum neutrophil gelatinase-associated lipocalin at day 3 was lower in the NEVKP group (1267 ± 372 vs 2697 ± 1145 ng/mL, P = 0.029). Continuous pressure-controlled NEVKP improves renal function in DCD kidney transplantation. Normothermic ex vivo kidney perfusion might help to decrease posttransplant delayed graft function rates and to increase the donor pool.

  2. MicroRNA-22 Is a Master Regulator of Bone Morphogenetic Protein-7/6 Homeostasis in the Kidney*

    PubMed Central

    Long, Jianyin; Badal, Shawn S.; Wang, Yin; Chang, Benny H. J.; Rodriguez, Antony; Danesh, Farhad R.

    2013-01-01

    Accumulating evidence suggests that microRNAs (miRNAs) contribute to a myriad of kidney diseases. However, the regulatory role of miRNAs on the key molecules implicated in kidney fibrosis remains poorly understood. Bone morphogenetic protein-7 (BMP-7) and its related BMP-6 have recently emerged as key regulators of kidney fibrosis. Using the established unilateral ureteral obstruction (UUO) model of kidney fibrosis as our experimental model, we examined the regulatory role of miRNAs on BMP-7/6 signaling. By analyzing the potential miRNAs that target BMP-7/6 in silica, we identified miR-22 as a potent miRNA targeting BMP-7/6. We found that expression levels of BMP-7/6 were significantly elevated in the kidneys of the miR-22 null mouse. Importantly, mice with targeted deletion of miR-22 exhibited attenuated renal fibrosis in the UUO model. Consistent with these in vivo observations, primary renal fibroblast isolated from miR-22-deficient UUO mice demonstrated a significant increase in BMP-7/6 expression and their downstream targets. This phenotype could be rescued when cells were transfected with miR-22 mimics. Interestingly, we found that miR-22 and BMP-7/6 are in a regulatory feedback circuit, whereby not only miR-22 inhibits BMP-7/6, but miR-22 by itself is induced by BMP-7/6. Finally, we identified two BMP-responsive elements in the proximal region of miR-22 promoter. These findings identify miR-22 as a critical miRNA that contributes to renal fibrosis on the basis of its pivotal role on BMP signaling cascade. PMID:24163368

  3. 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

  4. Evaluation of the ability of bone marrow derived cells to engraft the kidney and promote renal tubular regeneration in mice following exposure to cisplatin.

    PubMed

    Bataille, Aurélien; Galichon, Pierre; Wetzstein, Morgane; Legouis, David; Vandermeersch, Sophie; Rondeau, Eric; Hertig, Alexandre

    2016-01-01

    It has been suggested that bone marrow derived stem cells have the ability to engraft the kidney and improve the outcome of severe acute kidney injury (AKI) in mice exposed to high doses of cisplatin, providing hope for cancer patients in whom irreversible renal damage occasionally occurs following the use of this highly effective anti-tumor drug. We tested the therapeutic potential of bone marrow derived cells injected during the acute phase (day 3 after cisplatin administration) of experimentally-induced AKI in C57Bl6/J mice, characterized by massive tubular necrosis, apoptosis, and a low proliferation capacity. We failed to show any benefit of bone marrow derived cells versus a regular homogenate of intact renal cells, or normal saline. Using cell tracers and flow cytometry, we demonstrated that bone marrow derived cells did indeed home to the bone marrow of the recipients but failed to settle in the kidney. Conversely, renal cells homed to injured kidneys. However, neither cell therapy protected the animals against cisplatin-induced death. We therefore question the short-term efficacy of bone marrow derived cells used to repair established injuries of the tubular epithelium.

  5. Age-related changes in the function of autophagy in rat kidneys.

    PubMed

    Cui, Jing; Bai, Xue-Yuan; Shi, Suozhu; Cui, Shaoyuan; Hong, Quan; Cai, Guangyan; Chen, Xiangmei

    2012-04-01

    Autophagy is a highly regulated intracellular process for the degradation of cytoplasmic components, especially protein aggregates and damaged organelles. It is essential for maintaining healthy cells. Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. In this study, we investigated the effects of age on autophagy in the kidneys of 3-, 12-, and 24-month-old Fischer 344 rats. The results revealed that autophagy-related gene (Atg)7 was significantly downregulated in kidneys of increasing age. The protein expression level of the autophagy marker light chain 3/Atg8 exhibited a marked decline in aged kidneys. The levels of p62/SQSTM1 and polyubiquitin aggregates, representing the function of autophagy and proteasomal degradation, increased in older kidneys. The level of 8-hydroxydeoxyguanosine, a marker of mitochondrial DNA oxidative damage, was also increased in older kidneys. Analysis by transmission electron microscope demonstrated swelling and disintegration of cristae in the mitochondria of aged kidneys. These results suggest that autophagic function decreases with age in the kidneys of Fischer 344 rats, and autophagy may mediate the process of kidney aging, leading to the accumulation of damaged mitochondria.

  6. Bone quality and biomechanical function: a lesson from human ossicles.

    PubMed

    Duboeuf, François; Burt-Pichat, Brigitte; Farlay, Delphine; Suy, Paul; Truy, Eric; Boivin, Georges

    2015-04-01

    In humans, the middle ear contains a chain of three ossicles with a major highly specific mechanical property (transmission of vibrations) and modeling that stops rapidly after birth. Their bone quality has been rarely studied either in noninflammatory ossicles or in those from ears with chronic inflammation. Our primary goal was to assess bone microarchitecture, morphology and variables reflecting bone quality from incuses, in comparison with those from human femoral cortical bone as controls. Secondly, the impact of chronic inflammation on quality of ossicles was documented. The study was performed on 15 noninflammatory incuses from 15 patients (35±32 years, range: 2-91). Comparisons were performed with 13 inflammatory incuses from 13 patients (55±20 years, range: 1-79) with chronic inflammation of the middle ear, essentially cholesteatoma. Microarchitecture and bone mineral density (BMD) were assessed by microcomputed tomography. Microhardness was measured by microindentation. Mineral and organic characteristics were investigated by Fourier transform infrared microspectroscopy. Noninflammatory incuses were composed of a compact, well mineralized bone without bone marrow and with sparse vessels. Remodeling activity was rarely observed. Woven or lamellar textures and numerous osteocytes were observed. In inflammatory incuses, architecture was degraded, organic tissue was abundant and bone cavities contained fibrocellular tissue and adipocytes. BMD of noninflammatory incuses was significantly higher than BMD from both control bones (4 embedded cortical femoral bone samples; age: 72±15 years, range: 50-85) and inflammatory incuses. Noninflammatory incuses were less hard than both control bone (8 cortical femoral bone samples; age: 49±18 years, range: 24-74) and inflammatory incuses. All incuses were more mineralized and less mature than controls. In conclusion, bone quality of incuses (dense, well mineralized, hard) is well adapted to their function of sound

  7. Effect of low dose dopamine on early graft function in living unrelated kidney donors.

    PubMed

    Hosseinzadeh, Hamzeh; Golzari, Samad E J; Golzari, Samad; Abravesh, Mohammad; Mahmoodpoor, Ata; Aghamohammadi, Davood; Zomorrodi, Afshar; Hosseinzadeh, Parisa

    2012-01-01

    To evaluate the effect of low-dose dopamine administration on the early function of the kidney in unrelated kidney donors after transplantation. In this double-blinded clinical trial, 60 adult kidney donors and 60 recipients, younger than 50 years old, were studied. Donors and recipients were randomly divided into two groups; group 1 received dopamine 3 µ/kg/min and group 2 received similar regimen of placebo. During the first 3 days postoperatively, serum levels of urea and creatinine as well as urine output and early kidney function were compared between two groups. Serum levels of creatinine and urea and urine output during the first three days after the operation did not differ statistically significantly between two groups (P = .549, P = .306, and P = .375, respectively). Early kidney function was better significantly in group 1 (5.3 ± 3.2 versus 8.6 ± 8.0 hours; P = .048). Premedication of the kidney transplant donors with low-dose dopamine accelerates early kidney function after transplantation, but has no effect on the hemodynamic status and serum levels of creatinine and urea in the donors.

  8. Acute presentations of renal artery stenosis in three patients with a solitary functioning kidney.

    PubMed

    Pun, E; Dowling, R J; Mitchell, P J

    2004-12-01

    Renal artery stenosis can present uncommonly in the acute state as flash pulmonary oedema and hypertensive encephalopathy. We present three such cases in patients with a solitary functioning kidney, with successful management via renal artery angioplasty and stent insertion.

  9. Kidney function assessment and its role in drug development, review and utilization.

    PubMed

    Tortorici, Michael A; Nolin, Thomas D

    2014-07-01

    A key regulatory requirement pertaining to drug development is characterization of the role of kidney function in drug disposition and response, along with provision of corresponding renal dose adjustment recommendations. Traditionally, this information has been derived from Phase I pharmacokinetic studies in which regulatory guidance exists for pharmaceutical manufacturers on the design, conduct, analysis, and interpretation of data. Categorization and stratification of subjects into kidney function groups and dosing recommendations have historically been based on creatinine clearance estimates using the Cockcroft-Gault equation. As new estimating equations have emerged, the choice of equation for assessment of kidney function has become an area of debate. This review highlights these equations and provides recent examples of the use of quantitative models, incorporating efficacy and safety to make rational dose recommendations in subjects with impaired kidney function.

  10. Kidney Function as a Determinant of HDL and Triglyceride Concentrations in the Australian Population

    PubMed Central

    Thompson, Michael; Ray, Udayan; Yu, Richard; Hudspeth, Andrew; Smillie, Michael; Jordan, Neville; Bartle, Janet

    2016-01-01

    Background: Chronic kidney disease (CKD) is a potent risk factor for cardiovascular disease (CVD). CVD risk increases in a stepwise manner with increasing kidney impairment and is significantly reduced by kidney transplantation, suggesting a causal relationship. Dyslipidemia, a well recognised CVD risk factor, is highly prevalent in CKD. While dyslipidemia is a risk factor for CKD, kidney impairment can also induce a dyslipidemic state that may contribute to the excess burden of CVD in CKD. We utilised a multipronged approach to determine whether a causal relationship exists. Materials and Methods: Retrospective case-control analysis of 816 patients admitted to the Royal Hobart Hospital in 2008–2009 with different degrees of kidney impairment and retrospective before-after cohort analysis of 60 patients who received a transplanted kidney between 1999 and 2009. Results: Decreased estimated GFR (eGFR) was independently associated with decreased high density lipoprotein (HDL, p < 0.0001) and increased triglyceride concentrations (p < 0.01) in multivariate analysis. There was no significant relationship between eGFR and low density lipoprotein (LDL) or total cholesterol in multivariate analysis. Kidney transplantation increased HDL (p < 0.0001) and decreased triglyceride (p = 0.007) concentration, whereas there was no significant change in LDL and total cholesterol. These effects were dependent on maintenance of graft function, statin therapy (those who were on) if graft failure occurred then HDL again decreased and triglycerides increased. Conclusions: Kidney transplantation ameliorated alterations in plasma lipoprotein profile associated with kidney impairment, an effect that was dependent on the maintenance of graft function. These data suggest that kidney function is a determinant of HDL and triglyceride concentrations in patients with CKD. PMID:27005668

  11. Dietary interventions for mineral and bone disorder in people with chronic kidney disease.

    PubMed

    Liu, Zhuangzhu; Su, Guobin; Guo, Xinfeng; Wu, Yifan; Liu, Xusheng; Zou, Chuan; Zhang, Lei; Yang, Qianchun; Xu, Yuan; Ma, Weizhong

    2015-09-16

    Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic dysfunction of mineral and bone metabolism in people with CKD. Recent research shows that phosphate retention plays a significant role in the development of CKD-MBD. Compared with drug therapies, dietary interventions may be simple, inexpensive and feasible for phosphate retention. However, there is little evidence to support these interventions. Our objective was to assess the benefits and harms of any dietary intervention for preventing and treating CKD-MBD. We searched Cochrane Kidney and Transplant's Specialised Register to 27 August 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We also searched the Chinese Biomedicine Database (CBM) (1976 to August 2015), China Knowledge Resource Integrated Database (CNKI) (1979 to August 2015), and VIP (1989 to August 2015). Randomised controlled trials (RCTs) and quasi-RCTs looking at dietary interventions for prevention or treatment of CKD-MBD were eligible for inclusion. Two authors independently assessed the eligibility, methodological quality, and extracted data. Continuous outcomes (serum calcium level, serum phosphorus level, calcium × phosphate product, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23) and alkaline phosphatase) were expressed as mean difference (MD) with 95% confidence interval (CI). Dichotomous outcomes (mortality) were expressed as risk ratio (RR) with 95% CI. We used a random-effects model to meta-analyse studies. Nine studies were included in this review which analysed 634 participants. Study duration ranged from 4 to 24 weeks. The interventions included calcium-enriched bread, low phosphorus intake, low protein intake, very low protein intake, post haemodialysis supplements and hypolipaemic diet. Only one study reported death; none of the included studies reported cardiovascular events or fractures. There was insufficient reporting of design and

  12. 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.

  13. A Teaching Aid for Physiologists--Simulation of Kidney Function

    ERIC Educational Resources Information Center

    Packer, J. S.; Packer, J. E.

    1977-01-01

    Presented is the development of a simulation model of the facultative water transfer mechanism of the mammalian kidney. Discussion topics include simulation philosophy, simulation facilities, the model, and programming the model as a teaching aid. Graphs illustrate typical program displays. A listing of references concludes the article. (MA)

  14. A Teaching Aid for Physiologists--Simulation of Kidney Function

    ERIC Educational Resources Information Center

    Packer, J. S.; Packer, J. E.

    1977-01-01

    Presented is the development of a simulation model of the facultative water transfer mechanism of the mammalian kidney. Discussion topics include simulation philosophy, simulation facilities, the model, and programming the model as a teaching aid. Graphs illustrate typical program displays. A listing of references concludes the article. (MA)

  15. Apelin and copeptin: two opposite biomarkers associated with kidney function decline and cyst growth in autosomal dominant polycystic kidney disease.

    PubMed

    Lacquaniti, Antonio; Chirico, Valeria; Lupica, Rosaria; Buemi, Antoine; Loddo, Saverio; Caccamo, Chiara; Salis, Paola; Bertani, Tullio; Buemi, Michele

    2013-11-01

    Vasopressin (AVP) plays a detrimental role in autosomal dominant polycystic kidney disease (ADPKD). Copeptin represents a measurable substitute for circulating AVP whereas apelin counteracts AVP signaling. The aim of this study was to investigate the predictive value of apelin and copeptin for the progression of ADPKD disease. 52 ADPKD patients were enrolled and followed until the end of the observation period or the primary study endpoint was reached, defined by the combined outcome of decrease of glomerular filtration rate associated with a total renal volume increase. Receiver operating characteristics (ROC) analysis was employed for identifying the progression of renal disease and Kaplan-Meier curves assessed the renal survival. Adjusted risk estimates for progression endpoint and incident renal replacement therapy (RRT) were calculated using Cox proportional hazard regression analysis. ADPKD patients were characterized by lower apelin levels and higher copeptin levels when compared with healthy subjects. These biomarkers were strictly correlated with osmolality and markers of renal function. At ROC analysis, apelin and copeptin showed a very good diagnostic profile in identifying ADPKD progression. After the follow up of 24 months, 33 patients reached the endpoint. Cox proportional hazard regression analysis showed that apelin predicted renal disease progression and incident RRT independently of other potential confounders. Apelin is associated with kidney function decline in ADPKD, suggesting that it may be a new marker to predict kidney outcome.

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

    SciTech Connect

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

    1986-03-01

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

  17. Spatial mapping of functional pelvic bone marrow using FLT PET.

    PubMed

    McGuire, Sarah M; Menda, Yusuf; Boles Ponto, Laura L; Gross, Brandie; TenNapel, Mindi; Smith, Brian J; Bayouth, John E

    2014-07-08

    The purpose of this study was to determine the ability of regions identified with bony landmarks on CT imaging to accurately represent active bone marrow when compared to FLT PET imaging. These surrogate regions could then be used to create a bone marrow sparing radiation therapy plan when FLT PET imaging is not available. Whole body (WB) FLT PET images were obtained of 18 subjects prior to chemoradiation therapy. The FLT image of each subject was registered to a CT image acquired for that subject to obtain anatomic information of the pelvis. Seventeen regions were identified based on features of the pelvic bones, sacrum, and femoral heads. The probability of FLT uptake being located in each of 17 different CT-based regions of the bony pelvis was calculated using Tukey's multiple comparison test. Statistical analysis of FLT uptake in the pelvis indicated four distinct groups within the 17 regions that had similar levels of activity. Regions located in the central part of the pelvis, including the superior part of the sacrum, the inner halves of the iliac crests, and the L5 vertebral body, had greater FLT uptake than those in the peripheral regions (p-value < 0.05). We have developed a method to use CT-defined pelvic bone regions to represent FLT PET-identified functional bone marrow. Individual regions that have a statistically significant probability of containing functional bone marrow can be used as avoidance regions to reduce radiation dose to functional bone marrow in radiation therapy planning. However, because likely active bone marrow regions and pelvic targets typically overlap, patient-specific spatial detail may be advantageous in IMRT planning scenarios and may best be provided using FLT PET imaging.

  18. 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

  19. Prevascularisation with endothelial progenitor cells improved restoration of the architectural and functional properties of newly formed bone for bone reconstruction.

    PubMed

    Pang, Hao; Wu, Xue-Hui; Fu, Sheng-Long; Luo, Fei; Zhang, Ze-Hua; Hou, Tian-Yong; Li, Zhi-Qiang; Chang, Zheng-Qi; Yu, Bo; Xu, Jian-Zhong

    2013-04-01

    The aim of this study was to examine whether the addition of endothelial progenitor cells (EPCs) contributes to restoring the architectural and functional properties of newly formed bone for reconstruction of bone defects. Bone marrow-derived EPCs and mesenchymal stem cells (MSCs) were co-seeded onto demineralized bone matrix (DBM) as a prevascularized tissue-engineered bone (TEB) for the repair of segmental bone defects to evaluate the effects of prevascularization of TEB on ameliorating morphological, haemodynamic and mechanical characteristics. The restoration of the intraosseous vasculature and medullary cavity was improved markedly compared to the non-prevascularized groups. The blood supply, biomechanical strength, and bone mineral density of the prevascularized group were significantly higher than those of the non-prevascularized groups during bone reconstruction. The present study indicates that EPC-dependent prevascularization contributes to bone healing with structural reconstruction and functional recovery and may improve the understanding of correlation between angiogenesis and osteogenesis.

  20. Effect of telmisartan on kidney function in patients with chronic kidney disease: an observational study

    PubMed Central

    Agrawal, Ashish; Kamila, Shibnath; Reddy, Swetha; Lilly, Joyal; Mariyala, MS Sadhguna

    2016-01-01

    Abstract Background: Globally the burden of chronic kidney disease (CKD) is rising, an important cause of death and loss of disability-adjusted life years. Activation of the renin-angiotensin-aldosterone system is involved in its pathogenesis. The aim of the present study was to examine the effects of telmisartan (40 mg/day), an angiotensin receptor blocker (ARB) in Indian patients with CKD in real-life setting. Method: This was a prospective observational study. Fifty-six patients (>18 years) diagnosed with CKD were enrolled into the study. Serum creatinine, 24-h urinary protein, spot urine protein-to-creatinine ratio, glomerular filtration rate (GFR) and blood pressure (BP) were assessed along with safety. Results: A total of 55 patients (96.36% hypertensive; 63.61% diabetic) with mean age of 48.23 years completed the study. At the end of 3 months treatment with telmisartan, 24-h urinary protein, spot urine protein-to-creatinine, serum creatinine and BP significantly reduced (p < .05) by 806.78 mg, 0.95, 0.44 mg/dl and 8.9/4.7 mmHg in the overall population. GFR increased from the baseline value of 52.13 to 65.01 ml/min. Telmisartan was well tolerated and treatment was discontinued in one patient because of hyperkalemia. Conclusion: This study demonstrated that telmisartan effectively and safely reduces proteinuria in chronic kidney disease patients. PMID:27994942

  1. The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.

    PubMed

    Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P; Schreuder, Michiel F

    2016-01-01

    Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. © 2016 S. Karger AG, Basel.

  2. Antioxidant effects of maslinic acid in livers, hearts and kidneys of streptozotocin-induced diabetic rats: effects on kidney function.

    PubMed

    Mkhwanazi, Blessing N; Serumula, Metse R; Myburg, Rene B; Van Heerden, Fanie R; Musabayane, Cephas T

    2014-04-01

    Studies indicate that hyperglycemia-induced oxidative stress triggers the development of microvascular and macrovascular complications in diabetes. Accordingly, we hypothesized that maslinic acid (MA) prevents these complications due to its antioxidant properties. We, therefore, investigated the effects of 5-week MA treatment of streptozotocin (STZ)-induced diabetic rats on anti-oxidative status of cardiac, hepatic and renal tissues as well as on kidney function. Proximal tubular effects of MA were studied in anesthetized rats challenged with hypotonic saline after a 3.5 h equilibration for 4 h of 1 h control, 1.5 h treatment and 1.5 h recovery periods using lithium clearance. MA was added to the infusate during the treatment period. Oral glucose tolerance responses to MA were monitored in rats given a glucose load after an 18 h fast. Compared with untreated diabetic rats, MA-treated diabetic animals exhibited significantly low malondialdehyde (MDA, a marker of lipid peroxidation) and increased the activity of antioxidant enzymes; superoxide dismutase and glutathione peroxidase in hepatic, cardiac and renal tissues. The expressions of gastrocnemius muscle GLUT4 and kidney GLUT1 and GLUT2 were assessed to elucidate the mechanism of the hypoglycemic effects of MA. MA-treatment diminished the expression of GLUT1 and GLUT2 in diabetic kidney and reduced glycemia values of diabetic rats. MA administration increased urinary Na+ outputs and additionally the FENa indicating that at least part of the overall reduction in Na+ reabsorption occurred in the proximal tubules. These results suggest antioxidant effects of MA can ameliorate oxidative stress and improve kidney function in diabetes mellitus.

  3. Mediterranean Diet, Kidney Function, and Mortality in Men with CKD

    PubMed Central

    Jiménez-Moleón, José Juan; Lindholm, Bengt; Cederholm, Tommy; Ärnlöv, Johan; Risérus, Ulf; Sjögren, Per; Carrero, Juan Jesús

    2013-01-01

    Summary Background and objectives Adherence to a Mediterranean diet may link to a better preserved kidney function in the community as well as a favorable cardiometabolic profile and reduced mortality risk in individuals with manifest CKD. Design, setting, participants, & measurements Dietary habits were determined by 7-day dietary records in a population-based cohort of 1110 Swedish men (age 70 years) from 1991 to 1995, 506 of whom were considered to have CKD because of a GFR<60 ml/min per 1.73 m2. A Mediterranean Diet Score was calculated, and participants were categorized as having low, medium, or high adherence. Adequate dietary reporters were identified with Goldberg cutoffs (n=597). Deaths were registered during a median follow-up of 9.9 years. Results Compared with low adherents, medium and high adherents were 23% and 42% less likely to have CKD, respectively (adjusted odds ratio [95% confidence interval]=0.77 [0.57 to 1.05] and 0.58 [0.38 to 0.87], respectively, P for trend=0.04). Among those individuals with CKD, phosphate intake and net endogenous acid production were progressively lower across increasing adherence groups. No differences were observed regarding other cardiometabolic risk factors across adherence groups. As many as 168 (33%) CKD individuals died during follow-up. Compared with low adherents, proportional hazards regression associated medium and high adherents to a 25% and 23% lower mortality risk, respectively (adjusted hazard ratio [95% confidence interval]=0.75 [0.52 to 1.06] and 0.77 [0.44 to 1.36], respectively, P for trend=0.10). Sensitivity analyses showed significant and stronger associations when only adequate dietary reporters were considered. Conclusions Adherence to a Mediterranean dietary pattern is associated with lower likelihood of CKD in elderly men. A greater adherence to this diet independently predicted survival in those patients with manifest CKD. Clinical trials are warranted to test the hypothesis that following such

  4. 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.

  5. Modular flow chamber for engineering bone marrow architecture and function.

    PubMed

    Di Buduo, Christian A; Soprano, Paolo M; Tozzi, Lorenzo; Marconi, Stefania; Auricchio, Ferdinando; Kaplan, David L; Balduini, Alessandra

    2017-11-01

    The bone marrow is a soft, spongy, gelatinous tissue found in the hollow cavities of flat and long bones that support hematopoiesis in order to maintain the physiologic turnover of all blood cells. Silk fibroin, derived from Bombyx mori silkworm cocoons, is a promising biomaterial for bone marrow engineering, because of its tunable architecture and mechanical properties, the capacity of incorporating labile compounds without loss of bioactivity and demonstrated ability to support blood cell formation. In this study, we developed a bone marrow scaffold consisting of a modular flow chamber made of polydimethylsiloxane, holding a silk sponge, prepared with salt leaching methods and functionalized with extracellular matrix components. The silk sponge was able to support efficient platelet formation when megakaryocytes were seeded in the system. Perfusion of the chamber allowed the recovery of functional platelets based on multiple activation tests. Further, inhibition of AKT signaling molecule, which has been shown to be crucial in regulating physiologic platelet formation, significantly reduced the number of collected platelets, suggesting the applicability of this tissue model for evaluation of the effects of bone marrow exposure to compounds that may affect platelet formation. In conclusion, we have bioengineered a novel modular system that, along with multi-porous silk sponges, can provide a useful technology for reproducing a simplified bone marrow scaffold for blood cell production ex vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction Intervals.

    PubMed

    Yanik, Elizabeth L; Clarke, Christina A; Snyder, Jon J; Pfeiffer, Ruth M; Engels, Eric A

    2016-05-01

    Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin's lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin's lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin's lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention. Copyright © 2016 by the American Society of Nephrology.

  7. Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction Intervals

    PubMed Central

    Clarke, Christina A.; Snyder, Jon J.; Pfeiffer, Ruth M.; Engels, Eric A.

    2016-01-01

    Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin’s lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin’s lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin’s lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention. PMID:26563384

  8. Ethanol inhibits human bone cell proliferation and function in vitro

    SciTech Connect

    Friday, K.E.; Howard, G.A. )

    1991-06-01

    The direct effects of ethanol on human bone cell proliferation and function were studied in vitro. Normal human osteoblasts from trabecular bone chips were prepared by collagenase digestion. Exposure of these osteoblasts to ethanol in concentrations of 0.05% to 1% for 22 hours induced a dose-dependent reduction in bone cell DNA synthesis as assessed by incorporation of 3H-thymidine. After 72 hours of ethanol exposure in concentrations of 0.01% to 1%, protein synthesis as measured by 3H-proline incorporation into trichbroacetic acid (TCA)-precipitable material was reduced in a dose-dependent manner. Human bone cell protein concentrations and alkaline phosphatase total activity were significantly reduced after exposure to 1% ethanol for 72 hours, but not with lower concentrations of ethanol. This reduction in osteoblast proliferation and activity may partially explain the development of osteopenia in humans consuming excessive amounts of ethanol.

  9. Reducing bone cancer cell functions using selenium nanocomposites.

    PubMed

    Stolzoff, Michelle; Webster, Thomas J

    2016-02-01

    Cancer recurrence at the site of tumor resection remains a major threat to patient survival despite modern cancer therapeutic advances. Osteosarcoma, in particular, is a very aggressive primary bone cancer that commonly recurs after surgical resection, radiation, and chemotherapeutic treatment. The objective of the present in vitro study was to develop a material that could decrease bone cancer cell recurrence while promoting healthy bone cell functions. Selenium is a natural part of our diet which has shown promise for reducing cancer cell functions, inhibiting bacteria, and promoting healthy cells functions, yet, it has not been widely explored for osteosarcoma applications. For this purpose, due to their increased surface area, selenium nanoparticles (SeNP) were precipitated on a very common orthopedic tissue engineering material, poly-l-lactic acid (or PLLA). Selenium-coated PLLA materials were shown to selectively decrease long-term osteosarcoma cell density while promoting healthy, noncancerous, osteoblast functions (for example, up to two times more alkaline phosphatase activity on selenium coated compared to osteoblasts grown on typical tissue culture plates), suggesting they should be further studied for replacing tumorous bone tissue with healthy bone tissue. Importantly, results of this study were achieved without the use of chemotherapeutics or pharmaceutical agents, which have negative side effects.

  10. Characterizing microcrack orientation distribution functions in osteonal bone samples.

    PubMed

    Wolfram, U; Schwiedrzik, J J; Mirzaali, M J; Bürki, A; Varga, P; Olivier, C; Peyrin, F; Zysset, P K

    2016-12-01

    Prefailure microdamage in bone tissue is considered to be the most detrimental factor in defining its strength and toughness with respect to age and disease. To understand the influence of microcracks on bone mechanics it is necessary to assess their morphology and three-dimensional distribution. This requirement reaches beyond classic histology and stereology, and methods to obtain such information are currently missing. Therefore, the aim of the study was to develop a methodology that allows to characterize three-dimensional microcrack distributions in bulk bone samples. Four dumbbell-shaped specimens of human cortical bone of a 77-year-old female donor were loaded beyond yield in either tension, compression or torsion (one control). Subsequently, synchrotron radiation micro-computed tomography (SRμCT) was used to obtain phase-contrast images of the damaged samples. A microcrack segmentation algorithm was developed and used to segment microcrack families for which microcrack orientation distribution functions were determined. Distinct microcrack families were observed for each load case that resulted in distinct orientation distribution functions. Microcracks had median areas of approximately 4.7 μm(2) , 33.3 μm(2) and 64.0 μm(2) for tension, compression and torsion. Verifying the segmentation algorithm against a manually segmented ground truth showed good results when comparing the microcrack orientation distribution functions. A size dependence was noted when investigating the orientation distribution functions with respect to the size of the volume of interest used for their determination. Furthermore, a scale separation between tensile, compressive and torsional microcracks was noticeable. Visual comparison to classic histology indicated that microcrack families were successfully distinguished. We propose a methodology to analyse three-dimensional microcrack distributions in overloaded cortical bone. Such information could improve our understanding of

  11. Aortic Calcification and Femoral Bone Density Are Independently Associated with Left Ventricular Mass in Patients with Chronic Kidney Disease

    PubMed Central

    Chue, Colin D.; Wall, Nadezhda A.; Crabtree, Nicola J.; Zehnder, Daniel; Moody, William E.; Edwards, Nicola C.; Steeds, Richard P.; Townend, Jonathan N.; Ferro, Charles J.

    2012-01-01

    Background Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study. Methodology and Principal Findings A total of 120 patients were recruited (54% male, mean age 55±14 years, mean glomerular filtration rate 50±13 ml/min/1.73 m2). Abdominal aortic calcification was assessed using lateral lumbar spine radiography and was present in 48%. Mean femoral Z-score measured using dual energy x-ray absorptiometry was 0.60±1.06. Cardiovascular magnetic resonance imaging was used to determine left ventricular mass. One patient had left ventricular hypertrophy. Subjects with aortic calcification had higher left ventricular mass compared to those without (56±16 vs. 48±12 g/m2, P = 0.002), as did patients with femoral Z-scores below zero (56±15 vs. 49±13 g/m2, P = 0.01). In univariate analysis presence of aortic calcification correlated with left ventricular mass (r = 0.32, P = 0.001); mean femoral Z-score inversely correlated with left ventricular mass (r = −0.28, P = 0.004). In a multivariate regression model that included presence of aortic calcification, mean femoral Z-score, gender and 24-hour systolic blood pressure, 46% of the variability in left ventricular mass was explained (P<0.001). Conclusions In patients with stage 3 non-diabetic chronic kidney disease, lower mean femoral Z-score and presence of aortic calcification are independently associated with increased left ventricular mass. Further research exploring the pathophysiology that underlies these relationships is warranted. PMID:22723973

  12. Nonalcoholic fatty liver disease associated with impairment of kidney function in nondiabetes population

    PubMed Central

    Li, Guolin; Shi, Wang; Hu, Hui; Chen, Yaqin; Liu, Li; Yin, Dazhong

    2012-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is associated with the increased burden of kidney. However, there is still no large population study to explore the potential relationship between NAFLD and mild kidney function damage (MKFD) after adjusted for confounding factors. This study is to test the hypothesis that NAFLD is associated with MKFD under controlling the effects of confounding factors. Materials and methods: Levels of serum fasting glucose, creatinine, cholesterol, triglyceride, alanine aminotransferase and aspartate aminotransferase were analyzed from 1412 Chinese Han adults. Questionnaire and physical examination were performed to explore the potential association of NAFLD with kidney function. Results: NAFLD was associated with impairment of kidney function. Multivariate-adjusted odds ratio illustrated that, compared to subjects with normal liver, NAFLD subjects had a significantly higher risk of MKFD with or without adjusted for blood glucose and other covariates (P = 0.041). Further results from multi-interaction analysis demonstrated that the underlying mechanisms linked NAFLD with impaired kidney function may be that they share common risk factors and similar pathological processes. Conclusions: The most striking finding of this study is that NAFLD is negatively associated with kidney function, in nondiabetic population. NAFLD and MKFD may share similar risk factors and/or pathological processes. PMID:22384523

  13. Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease.

    PubMed

    Coca, Steven G; Nadkarni, Girish N; Huang, Yuan; Moledina, Dennis G; Rao, Veena; Zhang, Jane; Ferket, Bart; Crowley, Susan T; Fried, Linda F; Parikh, Chirag R

    2017-09-01

    Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D). At baseline, median concentrations of TNFR-1, TNFR-2, and KIM-1 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD population (ACCORD). In both cohorts, patients who reached the renal outcome had higher baseline levels than those who did not reach the outcome. Associations between doubling in TNFR-1, TNFR-2, and KIM-1 levels and risk of the renal outcomes were significant for both cohorts. Inclusion of these biomarkers in clinical models increased the area under the curve (SEM) for predicting the renal outcome from 0.68 (0.02) to 0.75 (0.02) in NEPHRON-D. Systematic review of the literature illustrated high consistency in the association between these biomarkers of inflammation and renal outcomes in DKD. In conclusion, TNFR-1, TNFR-2, and KIM-1 independently associated with higher risk of eGFR decline in persons with early or advanced DKD. Moreover, addition of these biomarkers to clinical prognostic models significantly improved discrimination for the renal outcome. Copyright © 2017 by the American Society of Nephrology.

  14. Sub-chronic Dermal Toxicity of Silver Nanoparticles in Guinea Pig: Special Emphasis to Heart, Bone and Kidney Toxicities.

    PubMed

    Korani, Mitra; Rezayat, Seyed Mahdi; Arbabi Bidgoli, Sepideh

    2013-01-01

    Silver nanoparticles (Ag NPs) have been widely used as new potent antimicrobial agents in cosmetic and hygienic products. Present study compares the tissue levels of Ag NPs in different organs of Guiana Pigs quantitatively after dermal application and analysis the morphological changes and pathological abnormalities on the basis of the Ag NPs tissue levels. Before toxicological assessments,the size of colloidal nanosilver was recorded by X-Ray Diffraction and Transmission Electron Microscope tests and the sizes of samples were recorded in sizes less than 100 nm. For toxicological evaluation, male guinea pigs were exposed to three concentrations of Ag NPs (100, 1000 and 10000 ppm) according to acute pretests for further assessments in subchronic model in a period of 13 weeks . A close correlation between dermal exposure and tissue levels of Ag NPs was found (p < 0.05) and tissue uptakes happened in dose dependent manner with the following ranking: ki dney>muscle>bone>skin>liver>heart >spleen. In histopathological studies, severe proximal convoluted tubule degeneration and distal convoluted tubule were seen in the kidneys of the middle and high-dose animals. Separated lines and marrow space narrow were determined as two major signs of bone toxicities which observed in three different dose levels of Ag NPs. Increased dermal dose of Ag NPs caused cardiocyte deformity, congestion and inflammation. The three different Ag NPs concentration gave comparable results for several endpoints measured in heart, bone and kidney, but differed in tissue concentrations and the extent of histopathological changes. It seems that Ag ions could be detected in different organs after dermal exposure ,which has the potential to provide target organ toxicities in a time and dose dependent manner.

  15. Adverse mandibular bone effects associated with kidney disease are only partially corrected with bisphosphonate and/or calcium treatment

    PubMed Central

    Allen, Matthew R.; Chen, Neal X.; Gattone, Vincent H.; Moe, Sharon M.

    2014-01-01

    Background/Aims Patients with chronic kidney disease (CKD) have high prevalence of periodontal disease that may predispose to tooth loss and inflammation. The goal of this study was to test the hypotheses that a genetic rat model of progressive CKD would exhibit altered oral bone properties and that treatment with either bisphosphonates or calcium could attenuate these adverse changes. Methods At 25 weeks of age, rats were treated with zoledronate, calcium gluconate, or their combination for 5 or 10 weeks. Mandible bone properties were assessed using micro-computed tomography to determine bone volume (BV/TV) and cement-enamel junction to alveolar crest distance (CEJ-AC). Results Untreated CKD animals had significantly lower BV/TV at both 30 (−5%) and 35 (−14%) weeks of age and higher CEJ-AC (+27 and 29%) compared to normal animals. CKD animals had significantly higher PTH compared to normal animals yet similar levels of C-reactive protein. Zoledronate-treatment normalized BV/TV over the first 5 weeks but this benefit was lost by 10 weeks. Calcium treatment, alone or in combination with zoledronate, was effective in normalizing BV/TV at both time points. Neither zoledronate nor calcium was able to correct the higher CEJ-AC caused by CKD. Calcium, but not zoledronate, significantly reduced serum parathyroid hormone (PTH) while neither treatment affected C-reactive protein. Conclusions 1) this progressive animal model of chronic kidney disease shows a clear mandibular skeletal phenotype consistent with periodontitis, 2) the periodontitis is not associated with systemic inflammation as measured by C-reactive protein, and 3) reducing PTH has positive effects on the mandible phenotype. PMID:24280830

  16. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    PubMed

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  17. Impact of Kidney Graft Weight-to-Recipient Body Weight Ratio on Long-Term Graft Function in Living Donor Kidney Transplant.

    PubMed

    Simforoosh, Nasser; Soltani, Mohammad Hossein; Kashi, Amirhossein; Basiri, Abbas; Tabibi, Ali; Narouie, Behzad; Yahyazadeh, Seyed Reza

    2017-10-01

    Our objective was to evaluate the effect of kidney graft weight-to-recipient body weight ratio as a nonimmune factor that may affect long-term graft function. We retrospectively collected data from 2531 living donor kidney transplant procedures performed between 1994 and 2010 at Shahid Labbafinejad Medical Center; 635 patients were included in this study. Each kidney was weighed after cold wash. The kidney weight-to-recipient body weight ratio was calculated. As an indicator of graft function, we used the Modification of Diet in Renal Disease Study Group equation to estimate glomerular filtration rate. For statistical analyses, we used simple linear regression analysis and the mixed model test using SPSS version 17.0 software (SPSS, Chicago, IL, USA). Mean age of recipients and median follow-up duration were 37.5 years (range, 6-77 y) and 36 months (range, 25-84 mo). Long-term graft function showed a positive correlation with kidney graft-to-recipient body weight ratio but not with the graft weight alone. The magnitude of this correlation was higher early after surgery (day 7) and decreased with long-term follow-up but was still statistically significant (P < .001). From our results, we conclude that kidney graft-to-recipient body weight ratio is correlated with the kidney graft function; graft size matching may be considered for kidney donor selection.

  18. Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease

    PubMed Central

    Finch, Jane L.; Tokumoto, Masanori; Nakamura, Hironori; Yao, Wei; Shahnazari, Mohammad; Lane, Nancy

    2010-01-01

    Calcimimetics activate the calcium-sensing receptor (CaR) and reduce parathyroid hormone (PTH) by increasing the sensitivity of the parathyroid CaR to ambient calcium. The calcimimetic, cinacalcet, is effective in treating secondary hyperparathyroidism in dialysis patients [chronic kidney disease (CKD 5)], but little is known about its effects on stage 3–4 CKD patients. We compared cinacalcet and paricalcitol in uremic rats with creatinine clearances “equivalent” to patients with CKD 3–4. Uremia was induced in anesthetized rats using the 5/6th nephrectomy model. Groups were 1) uremic control, 2) uremic + cinacalcet (U+Cin; 15 mg·kg−1·day−1 po for 6 wk), 3) uremic + paricalcitol (U+Par; 0.16 μg/kg, 3 × wk, ip for 6 wk), and 4) normal. Unlike U+Par animals, cinacalcet promoted hypocalcemia and marked hyperphosphatemia. The Ca × P in U+Cin rats was twice that of U+Par rats. Both compounds suppressed PTH. Serum 1,25-(OH)2D3 was decreased in both U+Par and U+Cin rats. Serum FGF-23 was increased in U+Par but not in U+Cin, where it tended to decrease. Analysis of tibiae showed that U+Cin, but not U+Par, rats had reduced bone volume. U+Cin rats had similar bone formation and reduced osteoid surface, but higher bone resorption. Hypocalcemia, hyperphosphatemia, low 1,25-(OH)2D3, and cinacalcet itself may play a role in the detrimental effects on bone seen in U+Cin rats. This requires further investigation. In conclusion, due to its effects on bone and to the hypocalcemia and severe hyperphosphatemia it induces, we believe that cinacalcet should not be used in patients with CKD without further detailed studies. PMID:20200094

  19. Differences of cell surface marker expression between bone marrow- and kidney-derived murine mesenchymal stromal cells and fibroblasts.

    PubMed

    Cakiroglu, F; Osbahr, J W; Kramer, J; Rohwedel, J

    2016-10-31

    Mesenchymal stromal cells (MSC) are undifferentiated, multipotent adult cells with regenerative properties. They are particularly relevant for therapeutic approaches due to the simplicity of their isolation and cultivation. Since MSC show an expression pattern of cell surface marker, which is almost identical to fibroblasts, many attempts have been made to address the similarities and differences between MSC and fibroblasts. In this study we aimed to isolate murine MSC from bone marrow (BM) and kidney to characterize them in comparison to fibroblasts. Cells were isolated from murine kidney, BM and abdominal skin by plastic adherence and subsequently characterized by analysing their capability to build colony-forming unit-fibroblasts (CFU-F), their morphology, their proliferation, expression of telomerase activity and cell surface antigens as well as their differentiation capacity. Plastic adherent cells from the 3 mouse tissues showed similar morphology, proliferation profiles and CFU-F building capacities. However, while MSC from BM and kidney differentiated into the adipogenic, chondrogenic and osteogenic direction, fibroblasts were not able to do so efficiently. In addition, a tendency for lower expression of telomerase was found in the fibroblast population. Proliferating cells from kidney and BM expressed the MSC-specific cell surface markers CD105 and Sca-1 on a significantly higher and CD117 on a significantly lower level compared to fibroblasts and were thereby distinguishable from fibroblasts. Furthermore, we found that certain CD markers were specifically expressed on a higher level, either in BM-derived cells or fibroblasts. This study demonstrates that murine MSC isolated from different organs express certain specific markers, which enable their discrimination.

  20. In patients with type 1 diabetes simultaneous pancreas and kidney transplantation preserves long-term kidney graft ultrastructure and function better than transplantation of kidney alone.

    PubMed

    Lindahl, Jørn P; Reinholt, Finn P; Eide, Ivar A; Hartmann, Anders; Midtvedt, Karsten; Holdaas, Hallvard; Dorg, Linda T; Reine, Trine M; Kolset, Svein O; Horneland, Rune; Øyen, Ole; Brabrand, Knut; Jenssen, Trond

    2014-11-01

    In patients with type 1 diabetes and end-stage renal disease (ESRD) we aimed to determine whether long-term normoglycaemia, as achieved by successful simultaneous pancreas and kidney (SPK) transplantation, would preserve kidney graft structure and function better than live donor kidney (LDK) transplantation alone. Estimated GFR (eGFR) was calculated in SPK (n = 25) and LDK (n = 17) recipients in a stable phase 3 months after transplantation and annually during follow-up. Kidney graft biopsies were obtained at follow-up for measurement of glomerular volume (light microscopy), glomerular basement membrane (GBM) and podocyte foot process widths and mesangial volume fraction (electron microscopy). SPK and LDK recipients were similar in age and diabetes duration at engraftment. Donor age was higher in the LDK group. Median follow-up time was 10.1 years. Mean HbA1c levels during follow-up were 5.5 ± 0.4% (37 ± 5 mmol/mol) and 8.3 ± 1.5% (68 ± 16 mmol/mol) in the SPK and LDK group, respectively (p < 0.001). Compared with SPK recipients, LDK recipients had wider GBM (369 ± 109 nm vs 281 ± 57 nm; p = 0.008) and increased mesangial volume fraction (median 0.23 [range 0.13-0.59] vs 0.16 [0.10-0.41]; p = 0.007) at follow-up. Absolute eGFR change from baseline was -11 ± 21 and -23 ± 15 ml min(-1) 1.73 m(-2) (p = 0.060), whereas eGFR slope was -1.1 (95% CI -1.7, -0.5) and -2.6 (95% CI -3.1, -2.1) ml min(-1) 1.73 m(-2) per year in the SPK and LDK group, respectively (p = 0.001). In patients with type 1 diabetes and long-term normoglycaemia after successful SPK transplantation, kidney graft ultrastructure and function were better preserved compared with LDK transplantation alone.

  1. Men and women in space: bone loss and kidney stone risk after long-duration spaceflight.

    PubMed

    Smith, Scott M; Zwart, Sara R; Heer, Martina; Hudson, Edgar K; Shackelford, Linda; Morgan, Jennifer Ll

    2014-07-01

    Bone loss, a key concern for long-duration space travelers, is typically considered a female issue. The number of women who have flown long-duration space missions is now great enough to allow a quantitative comparison of changes in bone and renal stone risk by sex. Participants were 42 astronauts (33 men and 9 women) on long-duration missions to the International Space Station. Bone mineral density (by dual-energy X-ray absorptiometry) and biochemical markers of bone metabolism (from blood and urine samples) were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. Missions were 49 to 215 days in duration, flown between 2000 and 2012. The bone density response to spaceflight was the same for men and women in both exercise groups. The bone mineral density response to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an advanced resistive exercise device. Biochemical markers of bone formation and resorption responded similarly in male and female astronauts. The response of urinary supersaturation risk to spaceflight was not significantly different between men and women, although risks were typically increased after flight in both groups, and risks were greater in men than in women before and after flight. The responses of men and women to spaceflight with respect to these measures of bone health were not different. © 2014 American Society for Bone and Mineral Research.

  2. 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.

  3. Wntless functions in mature osteoblasts to regulate bone mass.

    PubMed

    Zhong, Zhendong; Zylstra-Diegel, Cassandra R; Schumacher, Cassie A; Baker, Jacob J; Carpenter, April C; Rao, Sujata; Yao, Wei; Guan, Min; Helms, Jill A; Lane, Nancy E; Lang, Richard A; Williams, Bart O

    2012-08-14

    Recent genome-wide association studies of individuals of Asian and European descent have found that SNPs located within the genomic region (1p31.3) encoding the Wntless (Wls)/Gpr177 protein are associated significantly with reduced bone mineral density. Wls/Gpr177 is a newly identified chaperone protein that specifically escorts Wnt ligands for secretion. Given the strong functional association between the Wnt signaling pathways and bone development and homeostasis, we generated osteoblast-specific Wls-deficient (Ocn-Cre;Wls-flox) mice. Homozygous conditional knockout animals were born at a normal Mendelian frequency. Whole-body dual-energy X-ray absorptiometry scanning revealed that bone-mass accrual was significantly inhibited in homozygotes as early as 20 d of age. These homozygotes had spontaneous fractures and a high frequency of premature lethality at around 2 mo of age. Microcomputed tomography analysis and histomorphometric data revealed a dramatic reduction of both trabecular and cortical bone mass in homozygous mutants. Bone formation in homozygotes was severely impaired, but no obvious phenotypic change was observed in mice heterozygous for the conditional deletion. In vitro studies showed that Wls-deficient osteoblasts had a defect in differentiation and mineralization, with significant reductions in the expression of key osteoblast differentiation regulators. In summary, these results reveal a surprising and crucial role of osteoblast-secreted Wnt ligands in bone-mass accrual.

  4. Hematuria and decreased kidney function as initial signs of acute B-cell lymphoblastic leukemia.

    PubMed

    Seo-Mayer, Patricia; Kenney, Barton; McNamara, Joseph; Stein, Jeffrey; Moeckel, Gilbert W

    2010-11-01

    We report the case of a 14-year-old boy who presented with hematuria and decreased kidney function as initial manifestations of acute lymphoblastic leukemia (ALL). Computed tomography of the abdomen showed extensive retroperitoneal lymphadenopathy and bilateral nephromegaly. The patient's kidney biopsy specimen showed a dense monomorphous interstitial infiltrate of small round blue cells with significant nuclear atypia. Immunohistochemical workup showed positive staining for CD20, CD10, and terminal deoxynucleotidyl transferase (TdT), consistent with ALL. The patient underwent induction chemotherapy, attained remission 4 weeks after induction, and presently is stable in the consolidation phase of chemotherapy. This is an unusual case of ALL involving both kidneys with initial presenting signs of hematuria and decreased kidney function.

  5. Vicarious liver visualization in solitary functioning kidney with technetium-99m ethylenedicysteine renal scintigraphy

    PubMed Central

    Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Gupta, Nitin; Sood, Ashwani; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2015-01-01

    We present a case of 3-year-old boy who was incidentally diagnosed to have single left kidney on ultrasonography. Dynamic technetium-99m ethylenedicysteine renal scintigraphy was acquired for assessing the existing kidney function showed the tracer localization in bilateral renal fossae during the entire study. The single-photon emission computerized tomography/computerized tomography study revealed activity in the right renal fossa to be in the enlarged right lobe of the liver, which was mimicking as impaired functioning right kidney in planar images. The hybrid imaging helped in accurate delineation of tracer uptake by confirming it to be the false appearance of the right kidney in planar imaging. This case report also highlights the possible mechanism of renal tracer uptake in the liver parenchyma. PMID:26170576

  6. The Structure and Function of Non-Collagenous Bone Proteins

    NASA Technical Reports Server (NTRS)

    Hook, Magnus; McQuillan, David J.

    1997-01-01

    The research done under the cooperative research agreement for the project titled 'The structure and function of non-collagenous bone proteins' represented the first phase of an ongoing program to define the structural and functional relationships of the principal noncollagenous proteins in bone. An ultimate goal of this research is to enable design and execution of useful pharmacological compounds that will have a beneficial effect in treatment of osteoporosis, both land-based and induced by long-duration space travel. The goals of the now complete first phase were as follows: 1. Establish and/or develop powerful recombinant protein expression systems; 2. Develop and refine isolation and purification of recombinant proteins; 3. Express wild-type non-collagenous bone proteins; 4. Express site-specific mutant proteins and domains of wild-type proteins to enhance likelihood of crystal formation for subsequent solution of structure.

  7. Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet: association with hyperoxaluria, altered kidney and bone minerals, and renal tissue phospholipid-calcium interaction.

    PubMed

    Schmiedl, A; Schwille, P O; Bonucci, E; Erben, R G; Grayczyk, A; Sharma, V

    2000-12-01

    To determine whether an "atherogenic" diet (excess of cholesterol and neutral fat) induces pathological calcification in various organs, including the kidney, and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either normal lab chow (controls, n = 12) or the cholesterol- and fat-rich experimental diet (CH-F, n = 12) for 111 +/- 3 days. CH-F rats developed dyslipidemia [high blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low-density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol, total phospholipids], elevated serum total alkaline phosphatase and lactate dehydrogenase (LDH) levels, in the absence of changes in overall renal function, extracellular mineral homeostasis [serum protein-corrected total calcium, magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D)], plasma glycolate and oxalate levels. There was a redistribution of bone calcium and enhanced exchange of this within the extraosseous space, which was accompanied by significant bone calcium loss, but normal bone histomorphometry. Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were three times higher than in the controls. Urinary glycolate, oxalate, calcium and total protein excretion levels were elevated, the latter showing an excess of proteins > 100 kD and a deficit of proteins > 30-50 kD. Urinary calcium oxalate supersaturation was increased, and calcium phosphate supersaturation was unchanged. There were dramatically increased (by number, circumference, and area) renal calcium phosphate calcifications in the cortico-medullary region, but calcium oxalate deposits were not detectable. Electron microscopy (EM) and elemental analysis revealed intratubular calcium phosphate, apparently needle-like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed co-localization of phospholipids and calcium phosphate. It is concluded that rats fed the CH-F diet exhibited: (1) a

  8. Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function.

    PubMed

    Parikh, C R; Hall, I E; Bhangoo, R S; Ficek, J; Abt, P L; Thiessen-Philbrook, H; Lin, H; Bimali, M; Murray, P T; Rao, V; Schröppel, B; Doshi, M D; Weng, F L; Reese, P P

    2016-05-01

    Hypothermic machine perfusion (HMP) is increasingly used in deceased donor kidney transplantation, but controversy exists regarding the value of perfusion biomarkers and pump parameters for assessing organ quality. We prospectively determined associations between perfusate biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1, IL-18 and liver-type fatty acid-binding protein [L-FABP]) and pump parameters (resistance and flow) with outcomes of delayed graft function (DGF) and 6-mo estimated GFR (eGFR). DGF occurred in 230 of 671 (34%) recipients. Only 1-h flow was inversely associated with DGF. Higher NGAL or L-FABP concentrations and increased resistance were inversely associated with 6-mo eGFR, whereas higher flow was associated with higher adjusted 6-mo eGFR. Discarded kidneys had consistently higher median resistance and lower median flow than transplanted kidneys, but median perfusate biomarker concentrations were either lower or not significantly different in discarded compared with transplanted kidneys. Notably, most recipients of transplanted kidneys with isolated "undesirable" biomarker levels or HMP parameters experienced acceptable 6-mo allograft function, suggesting these characteristics should not be used in isolation for discard decisions. Additional studies must confirm the utility of combining HMP measurements with other characteristics to assess kidney quality.

  9. Impaired Function of Bone Marrow Stromal Cells in Systemic Mastocytosis

    PubMed Central

    Nemeth, K.; Wilson, T.M.; Ren, J.J.; Sabatino, M.; Stroncek, D.F.; Krepuska, M.; Bai, Y.; Robey, P.G.; Metcalfe, D.D.; Mezey, E.

    2015-01-01

    Patients with systemic mastocytosis (SM) have a wide variety of problems, including skeletal abnormalities. The disease results from a mutation of the stem cell receptor (c-kit) in mast cells and we wondered if the function of bone marrow stromal cells (BMSCs; also known as MSCs or mesenchymal stem cells) might be affected by the invasion of bone marrow by mutant mast cells. As expected, BMSCs from SM patients do not have a mutation in c-kit, but they proliferate poorly. In addition, while osteogenic differentiation of the BMSCs seems to be deficient, their adipogenic potential appears to be increased. Since the hematopoietic supportive abilities of BMSCs are also important, we also studied the engraftment in NSG mice of human CD34+ hematopoietic progenitors, after being co-cultured with BMSCs of healthy volunteers vs. BMSCs derived from patients with SM. BMSCs derived from the bone marrow of patients with SM could not support hematopoiesis to the extent that healthy BMSCs do. Finally, we performed an expression analysis and found significant differences between healthy and SM derived BMSCs in the expression of genes with a variety of functions, including the WNT signaling, ossification, and bone remodeling. We suggest that some of the symptoms associated with SM might be driven by epigenetic changes in BMSCs caused by dysfunctional mast cells in the bone marrow of the patients. PMID:26001169

  10. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.

    PubMed

    van Koppen, Arianne; Joles, Jaap A; van Balkom, Bas W M; Lim, Sai Kiang; de Kleijn, Dominique; Giles, Rachel H; Verhaar, Marianne C

    2012-01-01

    Chronic kidney disease (CKD) is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC) have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM) reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX) combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM) twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance) and effective renal plasma flow (PAH clearance) were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.

  11. Relationship between Fibroblast Growth Factor 23 and Biochemical and Bone Histomorphometric Alterations in a Chronic Kidney Disease Rat Model Undergoing Parathyroidectomy

    PubMed Central

    Liao, Hung-Wei; Hung, Peir-Haur; Hsiao, Chih-Yen; Liou, Hung-Hsiang; Lin, Hsin-Shih; Huang, Tsang-Hai; Jou, I-Ming; Tsai, Kuen-Jer

    2015-01-01

    Background Phosphate burden in chronic kidney disease (CKD) leads to elevated serum fibroblast factor-23 (FGF-23) levels, secondary hyperparathyroidism and chronic kidney disease-mineral bone disorder (CKD-MBD). However dissociated hyperphosphatemia and low serum FGF-23 concentrations have been observed in experimentally parathyoridectomized rats. The relationships between serum mineral, hormone, and bone metabolism may be altered in the presence of CKD. The aim of our study was to investigate whether a consistent relationship existed between serum FGF-23 levels, specific serum biochemical markers, and histomorphometric parameters of bone metabolism in a parathyroidectomized CKD animal model. Results Sprague Dawley rats were divided into 3 groups: parathyroidectomy (PTX) and CKD (PTX+CKD, 9 rats), CKD without PTX (CKD, 9 rats), and neither PTX nor CKD (sham-operated control, 8 rats); CKD was induced by partial nephrectomy. At 8 weeks after partial nephrectomy, serum biomarkers were measured. Bone histomorphometries of the distal femoral metaphyseal bone were analyzed. The mean serum FGF-23 levels and mean bone formation rate were the highest in the CKD group and the lowest in the PTX+CKD group. Bone volume parameters increased significantly in the PTX+CKD group. Pearson’s correlation revealed that serum FGF-23 levels associated with those of intact parathyroid hormone, phosphate, collagen type I C-telopeptide, and calcium. Univariate linear regression showed that serum FGF-23 values correlated with bone formation rate, bone volume, and osteoid parameters. Stepwise multivariate regression analysis revealed that circulating FGF-23 values were independently associated with bone volume and thickness (β = -0.737; p < 0.001 and β = -0.526; p = 0.006, respectively). Serum parathyroid hormone levels independently correlated with bone formation rate (β = 0.714; p < 0.001) while collagen type I C-telopeptide levels correlated with osteoid parameter. Conclusion Serum FGF

  12. Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment?

    PubMed

    Weaver, Virginia M; Kotchmar, Dennis J; Fadrowski, Jeffrey J; Silbergeld, Ellen K

    2016-01-01

    Biomonitoring has become a standard approach for exposure assessment in occupational and environmental epidemiology. The use of biological effect markers to identify early adverse changes in target organs has also become widely adopted. However, the potential for kidney function to affect biomarker levels in the body and the optimal approach to adjustment of biomarker concentrations in spot urine samples for hydration status are two important but underappreciated challenges associated with biomarker use. Several unexpected findings, such as positive associations between urine nephrotoxicant levels and estimated glomerular filtration rate (eGFR), have been reported recently in research using biomarkers. These and other findings, discussed herein, suggest an impact of kidney glomerular filtration or tubule processing on biomarker levels. This is more commonly raised in the context of decreased kidney filtration, traditionally referred to as reverse causality; however, recent data suggest that populations with normal kidney filtration may be affected as well. Misclassification bias would result if biomarkers reflect kidney function as well as either exposures or early biological effect outcomes. Furthermore, urine biomarker associations with eGFR that differ markedly by approach used to adjust for urine concentration have been reported. Associations between urine measures commonly used for this adjustment, such as urine creatinine, and specific research outcomes could alter observed biomarker associations with outcomes. Research recommendations to address the potential impact of kidney function and hydration status adjustment on biomarkers are provided, including a range of approaches to study design, exposure and outcome assessment, and adjustment for urine concentration.

  13. The transcriptome of the implant biopsy identifies donor kidneys at increased risk of delayed graft function.

    PubMed

    Mueller, T F; Reeve, J; Jhangri, G S; Mengel, M; Jacaj, Z; Cairo, L; Obeidat, M; Todd, G; Moore, R; Famulski, K S; Cruz, J; Wishart, D; Meng, C; Sis, B; Solez, K; Kaplan, B; Halloran, P F

    2008-01-01

    Improved assessment of donor organ quality at time of transplantation would help in management of potentially usable organs. The transcriptome might correlate with risk of delayed graft function (DGF) better than conventional risk factors. Microarray results of 87 consecutive implantation biopsies taken postreperfusion in 42 deceased (DD) and 45 living (LD) donor kidneys were compared to clinical and histopathology-based scores. Unsupervised analysis separated the 87 kidneys into three groups: LD, DD1 and DD2. Kidneys in DD2 had a greater incidence of DGF (38.1 vs. 9.5%, p < 0.05) than those in DD1. Clinical and histopathological risk scores did not discriminate DD1 from DD2. A total of 1051 transcripts were differentially expressed between DD1 and DD2, but no transcripts separated DGF from immediate graft function (adjusted p < 0.01). Principal components analysis revealed a continuum from LD to DD1 to DD2, i.e. from best to poorest functioning kidneys. Within DD kidneys, the odds ratio for DGF was significantly increased with a transcriptome-based score and recipient age (p < 0.03) but not with clinical or histopathologic scores. The transcriptome reflects kidney quality and susceptibility to DGF better than available clinical and histopathological scoring systems.

  14. [Frontiers in Live Bone Imaging Researches. Functional cross talk between bone and nervous system].

    PubMed

    Fukuda, Toru; Takeda, Shu

    2015-06-01

    Bone homeostasis is maintained by bone formation and bone resorption. The traditional view of bone metabolism as a primarily endocrine regulation has been expanded in recent years following the identification of nervous system controlling bone metabolism. Especially, sympathetic and parasympathetic nervous system regulates bone formation and bone resorption. In addition, sensory nervous system also has been shown to be involved in the regulation of bone homeostasis. These studies demonstrated that nervous system is closely related to bone remodeling.

  15. Is blood ammonia influenced by kidney function? A prospective study.

    PubMed

    Imran, Muhammad; Shah, Yaser; Nundlall, Seema; Roberts, Norman B; Howse, Matthew

    2012-03-01

    We have investigated whether blood ammonia is increased with worsening CKD. Fifty eight subjects with a range of CKD were recruited for analysis of plasma ammonia and other electrolytes. The concentrations of plasma ammonia were all within the normal reference range and there was no correlation between ammonia and CKD without any effect of dialysis. Blood ammonia is not elevated in or related to the severity of chronic kidney disease. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Maintenance of vascular integrity by pericytes is essential for normal kidney function.

    PubMed

    Lemos, Dario R; Marsh, Graham; Huang, Angela; Campanholle, Gabriela; Aburatani, Takahide; Dang, Lan; Gomez, Ivan; Fisher, Ken; Ligresti, Giovanni; Peti-Peterdi, Janos; Duffield, Jeremy S

    2016-12-01

    Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1(+) mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Loss of pericytes led to a rapid accumulation of neutral lipid vacuoles, swollen mitochondria, and apoptosis in tubular epithelial cells. Pericyte ablation led to endothelial cell swelling, reduced expression of vascular homeostasis markers, and peritubular capillary loss. Despite the observed injury, no signs of the acute inflammatory response were observed. Pathway enrichment analysis of genes expressed in kidney pericytes in vivo identified basement membrane proteins, angiogenic factors, and factors regulating vascular tone as major regulators of vascular function. Using novel microphysiological devices, we recapitulated human kidney peritubular capillaries coated with pericytes and showed that pericytes regulate permeability, basement membrane deposition, and microvascular tone. These findings suggest that through the active support of the microvasculature, pericytes are essential to adult kidney homeostasis.

  17. Splenic concentration of bone imaging agents in functional asplenia

    SciTech Connect

    Dhekne, R.D.

    1981-07-01

    Three cases of sickle cell disease associated with functional asplenia are described. The spleen was not visualized on routine Tc-99m-sulfur colloid scan. The bone scan performed with Tc-99m-phosphate compounds revealed abnormal splenic activity in all three cases. The previous case reports and the literature on this subject are reviewed.

  18. Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

    PubMed Central

    Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B.; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L. R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C. M.; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Chasman, Daniel I.; Kao, W. H. Linda; Fox, Caroline S.

    2012-01-01

    Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD. PMID:22479191

  19. Genome-wide association and functional follow-up reveals new loci for kidney function.

    PubMed

    Pattaro, Cristian; Köttgen, Anna; Teumer, Alexander; Garnaas, Maija; Böger, Carsten A; Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C M; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Goessling, Wolfram; Chasman, Daniel I; Kao, W H Linda; Fox, Caroline S

    2012-01-01

    Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

  20. Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children.

    PubMed

    Rodieux, Frederique; Wilbaux, Melanie; van den Anker, Johannes N; Pfister, Marc

    2015-12-01

    Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood has an impact not only on renal clearance but also on absorption, distribution, metabolism and nonrenal clearance of drugs. 'Omics'-based technologies, such as proteomics and metabolomics, can be leveraged to uncover novel markers for kidney function during normal development, acute kidney injury, and chronic diseases. Pharmacometric modeling and simulation can be applied to simplify the design of pediatric investigations, characterize the effects of kidney function on drug exposure and response, and fine-tune dosing in pediatric patients, especially in those with impaired kidney function. One case study of amikacin dosing in neonates with reduced kidney function is presented. Collaborative efforts between clinicians and scientists in academia, industry, and regulatory agencies are required to evaluate new renal biomarkers, collect and share prospective pharmacokinetic, genetic and clinical data, build integrated pharmacometric models for key drugs, optimize and standardize dosing strategies, develop bedside decision tools, and enhance labels of drugs utilized in neonates, infants, and children.

  1. [Bone metabolism and cardiovascular function update. Role of vitamin D in the bone and vascular intercommunication].

    PubMed

    Okano, Toshio

    2014-07-01

    Vascular calcification, hypertension and cardiac hypertrophy have been often complicated in osteoporotic patients with low bone mass. Since there are many similarities among the processes of bone formation and vascular calcification, vitamin D insufficiency has been thought to be deeply involved in the pathogenesis of these diseases. Indeed, in animal studies, vitamin D receptor gene knockout mice have been shown to display severe vascular calcification, high blood pressure, and left ventricular hypertrophy. On the other hand, in clinical studies, active vitamin D restores vascular calcification and improves heart function in dialysis patients. Whether 1,25 (OH) ₂D₃ acts directly on vascular smooth muscle cells and cardiomyocytes or acts indirectly on them via regulating calcium metabolism remains unclear. The elucidation of the role of vitamin D in the bone and vascular intercommunication and its application toward drug development could be an important step forward in the realization of health and longevity society.

  2. Pentoxifylline plus ACEIs/ARBs for proteinuria and kidney function in chronic kidney disease: a meta-analysis.

    PubMed

    Liu, Dong; Wang, Li-Na; Li, Hong-Xia; Huang, Ping; Qu, Liang-Bo; Chen, Fei-Yan

    2017-04-01

    Objective This meta-analysis aimed to investigate the efficacy and safety of pentoxifylline (PTF) plus angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) for proteinuria and kidney function in chronic kidney disease (CKD). Methods CENTRAL, EMBASE, Ovid-MEDLINE, PubMed, and CNKI were searched for relevant, randomized, controlled trials (RCTs). A meta-analysis was performed to review the effect of PTF plus ACEIs/ARBs vs. ACEIs/ARBs alone on proteinuria and kidney function in CKD. Results Eleven RCTs including 705 patients were retrieved. PTF plus ACEI/ARB treatment significantly decreased proteinuria in patients with CKD within 6 months (standard mean difference [SMD] -0.52; 95% CI -0.90 to 0.15; I(2 )= 68%) and significantly attenuated a decrease in estimated glomerular filtration rate (eGFR) in patients with stages 3-5 CKD after 6 months of treatment (standard mean difference [SMD] 0.30; confidence limit [Cl] 95% CI 0.06 to 0.54; I(2 )= 0%). PTF plus ACEIs/ARBs for 9 to 12 months significantly reduced albuminuria in patients with CKD (SMD-0.30, 95% CI -0.57 to 0.03; I(2 )= 0%) and alleviated the decline in eGFR in patients with stages 3-5 CKD (SMD 0.51; 95% CI 0.06 to 0.96; I(2 )= 61%). Conclusion The combination of an ACEI or ARB and PTF has a protective effect in reducing proteinuria by ameliorating the decline in eGFR in patients with stages 3-5 CKD.

  3. Low serum bicarbonate and kidney function decline: the Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Driver, Todd H; Shlipak, Michael G; Katz, Ronit; Goldenstein, Leonard; Sarnak, Mark J; Hoofnagle, Andrew N; Siscovick, David S; Kestenbaum, Bryan; de Boer, Ian H; Ix, Joachim H

    2014-10-01

    Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Retrospective cohort study. 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. Serum bicarbonate concentrations. Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. Cause of metabolic acidosis cannot be determined in this study. Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2). Copyright © 2014 National Kidney Foundation, Inc

  4. Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

    NASA Astrophysics Data System (ADS)

    Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra; Troppmann, Christoph; Demos, Stavros G.

    2017-05-01

    Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. The aim is to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. The signals were analyzed to obtain time constants, which were correlated to kidney dysfunction as determined by a subsequent survival study and histopathological analysis. Analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.

  5. Culture-modified bone marrow cells attenuate cardiac and renal injury in a chronic kidney disease rat model via a novel antifibrotic mechanism.

    PubMed

    Yuen, Darren A; Connelly, Kim A; Advani, Andrew; Liao, Christine; Kuliszewski, Michael A; Trogadis, Judy; Thai, Kerri; Advani, Suzanne L; Zhang, Yuan; Kelly, Darren J; Leong-Poi, Howard; Keating, Armand; Marsden, Philip A; Stewart, Duncan J; Gilbert, Richard E

    2010-03-04

    Most forms of chronic kidney disease are characterized by progressive renal and cardiac fibrosis leading to dysfunction. Preliminary evidence suggests that various bone marrow-derived cell populations have antifibrotic effects. In exploring the therapeutic potential of bone marrow derived cells in chronic cardio-renal disease, we examined the anti-fibrotic effects of bone marrow-derived culture modified cells (CMCs) and stromal cells (SCs). In vitro, CMC-conditioned medium, but not SC-conditioned medium, inhibited fibroblast collagen production and cell signalling in response to transforming growth factor-beta. The antifibrotic effects of CMCs and SCs were then evaluated in the 5/6 nephrectomy model of chronic cardio-renal disease. While intravascular infusion of 10(6) SCs had no effect, 10(6) CMCs reduced renal fibrosis compared to saline in the glomeruli (glomerulosclerosis index: 0.8+/-0.1 v 1.9+/-0.2 arbitrary units) and the tubulointersitium (% area type IV collagen: 1.2+/-0.3 v 8.4+/-2.0, p<0.05 for both). Similarly, 10(6) CMCs reduced cardiac fibrosis compared to saline (% area stained with picrosirius red: 3.2+/-0.3 v 5.1+/-0.4, p<0.05), whereas 10(6) SCs had no effect. Structural changes induced by CMC therapy were accompanied by improved function, as reflected by reductions in plasma creatinine (58+/-3 v 81+/-11 micromol/L), urinary protein excretion (9x/divided by 1 v 64x/divided by 1 mg/day), and diastolic cardiac stiffness (left ventricular end-diastolic pressure-volume relationship: 0.030+/-0.003 v 0.058+/-0.011 mm Hg/microL, p<0.05 for all). Despite substantial improvements in structure and function, only rare CMCs were present in the kidney and heart, whereas abundant CMCs were detected in the liver and spleen. Together, these findings provide the first evidence suggesting that CMCs, but not SCs, exert a protective action in cardio-renal disease and that these effects may be mediated by the secretion of diffusible anti-fibrotic factor(s).

  6. Culture-Modified Bone Marrow Cells Attenuate Cardiac and Renal Injury in a Chronic Kidney Disease Rat Model via a Novel Antifibrotic Mechanism

    PubMed Central

    Advani, Andrew; Liao, Christine; Kuliszewski, Michael A.; Trogadis, Judy; Thai, Kerri; Advani, Suzanne L.; Zhang, Yuan; Kelly, Darren J.; Leong-Poi, Howard; Keating, Armand; Marsden, Philip A.; Stewart, Duncan J.; Gilbert, Richard E.

    2010-01-01

    Background Most forms of chronic kidney disease are characterized by progressive renal and cardiac fibrosis leading to dysfunction. Preliminary evidence suggests that various bone marrow-derived cell populations have antifibrotic effects. In exploring the therapeutic potential of bone marrow derived cells in chronic cardio-renal disease, we examined the anti-fibrotic effects of bone marrow-derived culture modified cells (CMCs) and stromal cells (SCs). Methodology/Principal Findings In vitro, CMC-conditioned medium, but not SC-conditioned medium, inhibited fibroblast collagen production and cell signalling in response to transforming growth factor-ß. The antifibrotic effects of CMCs and SCs were then evaluated in the 5/6 nephrectomy model of chronic cardio-renal disease. While intravascular infusion of 106 SCs had no effect, 106 CMCs reduced renal fibrosis compared to saline in the glomeruli (glomerulosclerosis index: 0.8±0.1 v 1.9±0.2 arbitrary units) and the tubulointersitium (% area type IV collagen: 1.2±0.3 v 8.4±2.0, p<0.05 for both). Similarly, 106 CMCs reduced cardiac fibrosis compared to saline (% area stained with picrosirius red: 3.2±0.3 v 5.1±0.4, p<0.05), whereas 106 SCs had no effect. Structural changes induced by CMC therapy were accompanied by improved function, as reflected by reductions in plasma creatinine (58±3 v 81±11 µmol/L), urinary protein excretion (9×/÷1 v 64×/÷1 mg/day), and diastolic cardiac stiffness (left ventricular end-diastolic pressure-volume relationship: 0.030±0.003 v 0.058±0.011 mm Hg/µL, p<0.05 for all). Despite substantial improvements in structure and function, only rare CMCs were present in the kidney and heart, whereas abundant CMCs were detected in the liver and spleen. Conclusions/Significance Together, these findings provide the first evidence suggesting that CMCs, but not SCs, exert a protective action in cardio-renal disease and that these effects may be mediated by the secretion of diffusible anti

  7. Kidney function and cerebral small vessel disease in the general population.

    PubMed

    Akoudad, Saloua; Sedaghat, Sanaz; Hofman, Albert; Koudstaal, Peter J; van der Lugt, Aad; Ikram, M Arfan; Vernooij, Meike W

    2015-06-01

    Anatomic and hemodynamic similarities between renal and cerebral vessels suggest a tight link between kidney disease and brain disease. Although several distinct markers are used to identify subclinical kidney and brain disease, a comprehensive assessment of how these markers link damage at both end organs is lacking. To investigate whether measures of kidney function were associated with cerebral small vessel disease on MRI. In 2526 participants of the population-based Rotterdam Study, we measured urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate based on serum creatinine and cystatin C. All participants underwent brain magnetic resonance imaging. We assessed presence of cerebral small vessel disease by calculating white matter lesion volumes and rating the presence of lacunes and cerebral microbleeds. We used multivariable linear and logistic regression to investigate the association between kidney function and cerebral small vessel disease. Worse kidney function was consistently associated with a larger white matter lesion volume (mean difference per standard deviation increase in albumin-to-creatinine ratio: 0.09, 95% confidence interval 0.05; 0.12; per standard deviation decrease in creatinine-based estimated glomerular filtration rate: -0.04, 95% confidence interval -0.08;-0.01, and per standard deviation decrease in cystatin C-based estimated glomerular filtration rate: -0.09, 95% confidence interval -0.13;-0.05). Persons with higher albumin-to-creatinine ratio or lower cystatin C-based estimated glomerular filtration rate levels had a higher prevalence of lacunes (odds ratio per standard deviation increase in albumin-to-creatinine ratio: 1.24, 95% confidence interval 1.07; 1.43). Only participants in the highest quartile of albumin-to-creatinine ratio had a higher frequency of microbleeds compared to the lowest quartile. Worse kidney function is associated with cerebral small vessel disease. Of all measures of kidney function, in

  8. 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

  9. Extracellular pH regulates bone cell function.

    PubMed

    Arnett, Timothy R

    2008-02-01

    The skeletons of land vertebrates contain a massive reserve of alkaline mineral (hydroxyapatite), which is ultimately available to buffer metabolic H+ if acid-base balance is not maintained within narrow limits. The negative impact of acidosis on the skeleton has long been known but was thought to result from passive, physicochemical dissolution of bone mineral. This brief, selective review summarizes what is now known of the direct functional responses of bone cells to extracellular pH. We discovered that bone resorption by cultured osteoclasts is stimulated directly by acid. The stimulatory effect is near-maximal at pH 7.0, whereas above pH 7.4, resorption is switched off. In bone organ cultures, H+-stimulated bone mineral release is almost entirely osteoclast-mediated, with a negligible physicochemical component. Acidification is the key requirement for osteoclasts to excavate resorption pits in all species studied to date, and extracellular H+ may thus be regarded as the long-sought osteoclast activation factor. Acid-activated osteoclasts can be stimulated further by agents such as parathyroid hormone, 1,25-dihydroxycholecalciferol, and receptor activator of nuclear factor kappaB ligand. Osteoclasts may respond to pH changes via H+-sensing ion channels such as transient receptor potential vanilloid 1, a nociceptor that is also activated by capsaicin. Acidosis also exerts a powerful, reciprocal inhibitory effect on the mineralization of bone matrix by cultured osteoblasts. This is caused by increased hydroxyapatite solubility at low pH, together with selective inhibition of alkaline phosphatase, which is required for mineralization. Diets or drugs that shift acid-base balance in the alkaline direction may provide useful treatments for bone loss disorders.

  10. PHYSICAL ACTIVITY AND RAPID DECLINE IN KIDNEY FUNCTION AMONG OLDER ADULTS

    PubMed Central

    Robinson-Cohen, Cassianne; Katz, Ronit; Mozaffarian, Dariush; Dalrymple, Lorien S; de Boer, Ian; Sarnak, Mark; Shlipak, Mike; Siscovick, David; Kestenbaum, Bryan

    2010-01-01

    BACKGROUND Physical activity promotes diverse metabolic benefits that may moderate the long-term risk of progressive kidney dysfunction. OBJECTIVE To test the hypothesis that greater physical activity is associated with a lower risk of rapid kidney function decline among a general population of older adults. DESIGN Prospective cohort study of community-dwelling older men and women. SETTING Community-based sample in 4 U.S. sites recruited from Medicare eligibility files. PARTICIPANTS A total of 5888 men and women aged 65 years or older participating in the Cardiovascular Health Study. Participants who did not complete at least two measurements of kidney function, those who were unable to complete basic household chores, and those with missing physical activity data were excluded, leaving 4011 participants for analysis. MAIN EXPOSURE MEASURE Physical activity score calculated by summation of leisure-time activity (ordinal score of 1–5 for quintiles of 105, 480, 1012.5, and 2089 kilocalories per week) and walking pace (ordinal score of 1–3 for categories of less than 2, 2–3, and greater than 3 miles per hour). MAIN OUTCOME MEASURE Rapid kidney function decline, defined by the loss of >3.0 mL/min per 1.73 m2 per year in the estimated glomerular filtration rate, calculated using longitudinal serum measurements of cystatin C. RESULTS There were 958 participants (23.9%) with a rapid decline in kidney function, (4.1 events per 100 person-years). The estimated risk of rapid kidney function decline was 16% in the highest physical activity group and 30% in the lowest physical activity group. After full adjustment for demographics, clinical, and subclinical disease characteristics, the two highest physical activity groups were associated with a 28% lower (95% CI: 21% to 41% lower) risk of rapid kidney function decline, compared to the two lowest physical activity groups. Greater kilocalories of leisure time physical activity, walking pace, and exercise intensity were

  11. Effects of Chinese herbal medicine on bone structure and function.

    PubMed

    Xu, Hong; Lawson, David

    2004-09-01

    This study examined the effects of four-months of treatment using Chinese herbal Shu Di Shan Zha Formula on bone health. Fourteen Australian menopausal women participated in this paired study and completed all the tests at the commencement, 4th month (when the treatment group and control group cross over) and the 8th month (end) of the study. Data from bone structure and function tests (broadband ultrasonic attenuation--BUA and velocity of sound--VOS), biomarkers of bone turnover (osteocalcin--OSTN and urinary pyridum crosslinks--PYR and D-PYR) were collected from each subject. Results showed that Shu Di Shan Zha Formula was able to affect the level of BUA, and reduce the level of D-PYR in menopausal women.

  12. Blood flow controls bone vascular function and osteogenesis

    PubMed Central

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Schiller, Maria; Zeuschner, Dagmar; Bixel, M. Gabriele; Milia, Carlo; Gamrekelashvili, Jaba; Limbourg, Anne; Medvinsky, Alexander; Santoro, Massimo M.; Limbourg, Florian P.; Adams, Ralf H.

    2016-01-01

    While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system. PMID:27922003

  13. 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.

  14. [Bone metabolism and cardiovascular function update. Inter-communication between bone marrow hematopoiesis and skeletal/vascular network].

    PubMed

    Katayama, Yoshio

    2014-07-01

    The hematopoiesis takes place in the bone marrow. Because bone marrow is the "marrow" of the bone, bone marrow does not exist without bone. The specialized microenvironment for hematopoietic stem cells (HSCs) to be appropriately functional is called "niche" . In the recent ten years since the bone-forming osteoblast was identified as a HSC niche, the entire mesenchymal lineage cells from mesenchymal stem cells to end-terminal osteocytes have been recognized as niche cells or niche-modulators. Among these, mesenchymal stem/progenitor cells are located at perivascular area. The very recent study showed the difference between arteriolar and sinusoidal niches. It is likely that the vascular network and the bone tissue are connected by the mesenchymal lineage cells as a complex of bone forming system, and HSCs utilize this complex as a series of niche.

  15. Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration

    PubMed Central

    Zhang, Xingdi; Zeng, Deliang; Li, Nan; Wen, Jin; Jiang, Xinquan; Liu, Changsheng; Li, Yongsheng

    2016-01-01

    Mesoporous bioactive glass (MBG), which possesses excellent bioactivity, biocompatibility and osteoconductivity, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with high compressive strength for applications in bone regeneration; this difficulty has greatly hindered its development and use. To solve this problem, a simple powder processing technique has been successfully developed to fabricate a novel type of MBG scaffold (MBGS). Furthermore, amino or carboxylic groups could be successfully grafted onto MBGSs (denoted as N-MBGS and C-MBGS, respectively) through a post-grafting process. It was revealed that both MBGS and the functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bMSCs. Due to its positively charged surface, N-MBGS presented the highest in vitro osteogenic capability of the three samples. Moreover, in vivo testing results demonstrated that N-MBGS could promote higher levels of bone regeneration compared with MBGS and C-MBGS. In addition to its surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in promoting bone regeneration. These findings indicate that MBGSs are promising materials with potential practical applications in bone regeneration, which can be successfully fabricated by combining a powder processing technique and post-grafting process. PMID:26763311

  16. Relation between kidney function, proteinuria, and adverse outcomes.

    PubMed

    Hemmelgarn, Brenda R; Manns, Braden J; Lloyd, Anita; James, Matthew T; Klarenbach, Scott; Quinn, Robert R; Wiebe, Natasha; Tonelli, Marcello

    2010-02-03

    The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system. To determine the association between reduced GFR, proteinuria, and adverse clinical outcomes. Community-based cohort study with participants identified from a province-wide laboratory registry that includes eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). All-cause mortality, myocardial infarction, and progression to kidney failure. The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m(2) or greater. Over median follow-up of 35 months (range, 0-59 months), 27 959 participants (3.0%) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60 mL/min/1.73 m(2) or greater, as compared with those with eGFR of 45 to 59.9 mL/min/1.73 m(2) and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs 2.9 [95% CI, 2.7-3.0] per 1000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. The risks of mortality

  17. Morphological and functional characteristics of three-dimensional engineered bone-ligament-bone constructs following implantation.

    PubMed

    Ma, Jinjin; Goble, Kristen; Smietana, Michael; Kostrominova, Tatiana; Larkin, Lisa; Arruda, Ellen M

    2009-10-01

    The incidence of ligament injury has recently been estimated at 400,000/year. The preferred treatment is reconstruction using an allograft, but outcomes are limited by donor availability, biomechanical incompatibility, and immune rejection. The creation of an engineered ligament in vitro solely from patient bone marrow stromal cells (has the potential to greatly enhance outcomes in knee reconstructions. Our laboratory has developed a scaffoldless method to engineer three-dimensional (3D) ligament and bone constructs from rat bone marrow stem cells in vitro. Coculture of these two engineered constructs results in a 3D bone-ligament-bone (BLB) construct with viable entheses, which was successfully used for medial collateral ligament (MCL) replacement in a rat model. 1 month and 2 month implantations were applied to the engineered BLBs. Implantation of 3D BLBs in a MCL replacement application demonstrated that our in vitro engineered tissues grew and remodeled quickly in vivo to an advanced phenotype and partially restored function of the knee. The explanted 3D BLB ligament region stained positively for type I collagen and elastin and was well vascularized after 1 and 2 months in vivo. Tangent moduli of the ligament portion of the 3D BLB 1 month explants increased by a factor of 2.4 over in vitro controls, to a value equivalent to those observed in 14-day-old neonatal rat MCLs. The 3D BLB 1 month explants also exhibited a functionally graded response that closely matched native MCL inhomogeneity, indicating the constructs functionally adapted in vivo.

  18. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation best characterizes kidney function in patients being considered for lung transplantation.

    PubMed

    Osho, Asishana A; Castleberry, Anthony W; Snyder, Laurie D; Palmer, Scott M; Stafford-Smith, Mark; Lin, Shu S; Duane Davis, R; Hartwig, Matthew G

    2014-12-01

    Methods for direct measurement of glomerular filtration rate (GFR) are expensive and inconsistently applied across transplant centers. The Modified Diet in Renal Disease (MDRD) equation is commonly used for GFR estimation, but is inaccurate for GFRs >60 ml/min per 1.73 m(2). The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) and Wright equations have shown improved predictive capabilities in some patient populations. We compared these equations to determine which one correlates best with direct GFR measurement in lung transplant candidates. We conducted a retrospective cohort analysis of 274 lung transplant recipients. Pre-operative GFR was measured directly using a radionuclide GFR assay. Results from the MDRD, CKDEPI, Wright, and Cockroft-Gault equations were compared with direct measurement. Findings were validated using logistic regression models and receiver operating characteristic (ROC) analyses in looking at GFR as a predictor of mortality and renal function outcomes post-transplant. Assessed against the radionuclide GFR measurement, CKDEPI provided the most consistent results, with low values for bias (0.78), relative standard error (0.03) and mean absolute percentage error (15.02). Greater deviation from radionuclide GFR was observed for all other equations. Pearson's correlation between radionuclide and calculated GFR was significant for all equations. Regression and ROC analyses revealed equivalent utility of the radionuclide assay and GFR equations for predicting post-transplant acute kidney injury and chronic kidney disease (p < 0.05). In patients being evaluated for lung transplantation, CKDEPI correlates closely with direct radionuclide GFR measurement and equivalently predicts post-operative renal outcomes. Transplant centers could consider replacing or supplementing direct GFR measurement with less expensive, more convenient estimation by using the CKDEPI equation. Copyright © 2014 International Society for Heart and Lung

  19. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation best characterizes kidney function in patients being considered for lung transplantation

    PubMed Central

    Osho, Asishana A.; Castleberry, Anthony W.; Snyder, Laurie D.; Palmer, Scott M.; Stafford-Smith, Mark; Lin, Shu S.; Davis, R. Duane; Hartwig, Matthew G.

    2015-01-01

    BACKGROUND Methods for direct measurement of glomerular filtration rate (GFR) are expensive and inconsistently applied across transplant centers. The Modified Diet in Renal Disease (MDRD) equation is commonly used for GFR estimation, but is inaccurate for GFRs > 60 ml/min per 1.73 m2. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) and Wright equations have shown improved predictive capabilities in some patient populations. We compared these equations to determine which one correlates best with direct GFR measurement in lung transplant candidates. METHODS We conducted a retrospective cohort analysis of 274 lung transplant recipients. Pre-operative GFR was measured directly using a radionuclide GFR assay. Results from the MDRD, CKDEPI, Wright, and Cockroft–Gault equations were compared with direct measurement. Findings were validated using logistic regression models and receiver operating characteristic (ROC) analyses in looking at GFR as a predictor of mortality and renal function outcomes post-transplant. RESULTS Assessed against the radionuclide GFR measurement, CKDEPI provided the most consistent results, with low values for bias (0.78), relative standard error (0.03) and mean absolute percentage error (15.02). Greater deviation from radionuclide GFR was observed for all other equations. Pearson’s correlation between radionuclide and calculated GFR was significant for all equations. Regression and ROC analyses revealed equivalent utility of the radionuclide assay and GFR equations for predicting post-transplant acute kidney injury and chronic kidney disease (p < 0.05). CONCLUSIONS In patients being evaluated for lung transplantation, CKDEPI correlates closely with direct radionuclide GFR measurement and equivalently predicts post-operative renal outcomes. Transplant centers could consider replacing or supplementing direct GFR measurement with less expensive, more convenient estimation by using the CKDEPI equation. PMID:25107351

  20. Sodium Intake as a Modulator of Kidney Function.

    PubMed

    Krekels, Marielle M E; Kroon, Abraham A; de Leeuw, Peter W

    2015-01-01

    Individual responses to alterations in salt intake vary widely. While salt has no effect on blood pressure in some people, it may substantially increase pressure in others. The reason why this difference exists is not very clear yet but many observations point towards the kidney as an important mediator. The adaptation in urinary output of sodium after a salt challenge (increase or decrease) also is not uniform. It is thought that the renin-angiotensin system may play an important role in determining how much sodium the body expels or retains after salt intake is suddenly reduced or augmented. Recent data suggest that the peptide Ang (1-7) and the endogenous nitric oxide inhibitor asymmetric dimethylarginine could be critically involved in the regulation of the renal response to altered salt intake.

  1. [Changes of bone morphogenetic protein-7 and inhibitory Smad expression in streptozotocin-induced diabetic nephropathy rat kidney].

    PubMed

    Yang, Qin; Han, Bing; Xie, Ru-Jia; Cheng, Ming-Liang

    2007-04-25

    The present study was designed to observe the expressions of bone morphogenetic protein-7 (BMP-7) and inhibitory Smads in kidney of rats with diabetic nephropathy (DN), and explore the possible mechanism of DN. Male Wistar rats weighing 180-220 g were single injected with streptozocin (STZ, 55 mg/kg body weight) for 2, 4, 8 and 16 weeks to induce DN. Blood glucose, kidney weight/body weight and 24-hour urine protein in the control and DN rats were examined; the expressions of BMP-7, Smad6 and Smad7 were detected by using immunohistochemical techniques, Western blot and real-time PCR. The results showed that blood glucose and 24-hour urine protein in DN rats were higher than that in the control rats and kidney weight/body weight was also elevated in DN rats, especially in 16-week STZ-induced rats. The expressions of BMP-7 and Smad6 proteins in DN rats were elevated, while BMP-7 mRNA expression was increased 2 weeks after STZ injection and decreased 16 weeks after STZ injection. The expressions of Smad7 protein and mRNA were elevated in DN rats 2 weeks after STZ injection and decreased 16 weeks after STZ injection. In addition, the expressions of transforming growth factor-beta1 (TGF-beta1) and collagen type I (COL-I) mRNA were increased in DN rats. These results suggest in the early stage of DN, increase in BMP-7 and inhibitory Smad expression may play a role in the feedback regulation and restrain the development of DN.

  2. Reduced Renal Calcium Excretion in the Absence of Sclerostin Expression: Evidence for a Novel Calcium-Regulating Bone Kidney Axis

    PubMed Central

    Vallon, Volker

    2014-01-01

    The kidneys contribute to calcium homeostasis by adjusting the reabsorption and excretion of filtered calcium through processes that are regulated by parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3). Most of the filtered calcium is reabsorbed in the proximal tubule, primarily by paracellular mechanisms that are not sensitive to calcium-regulating hormones in physiologically relevant ways. In the distal tubule, however, calcium is reabsorbed by channels and transporters, the activity or expression of which is highly regulated and increased by PTH and 1α,25(OH)2D3. Recent research suggests that other, heretofore unrecognized factors, such as the osteocyte-specific protein sclerostin, also regulate renal calcium excretion. Clues in this regard have come from the study of humans and mice with inactivating mutations of the sclerostin gene that both have increased skeletal density, which would necessitate an increase in intestinal absorption and/or renal reabsorption of calcium. Deletion of the sclerostin gene in mice significantly diminishes urinary calcium excretion and increases fractional renal calcium reabsorption. This is associated with increased circulating 1α,25(OH)2D3 levels, whereas sclerostin directly suppresses 1α-hydroxylase in immortalized proximal tubular cells. Thus, evidence is accumulating that sclerostin directly or indirectly reduces renal calcium reabsorption, suggesting the presence of a novel calcium-excreting bone-kidney axis. PMID:24876121

  3. DNA methylation profile associated with rapid decline in kidney function: findings from the CRIC Study

    PubMed Central

    Wing, Maria R.; Devaney, Joseph M.; Joffe, Marshall M.; Xie, Dawei; Feldman, Harold I.; Dominic, Elizabeth A.; Guzman, Nicolas J.; Ramezani, Ali; Susztak, Katalin; Herman, James G.; Cope, Leslie; Harmon, Brennan; Kwabi-Addo, Bernard; Gordish-Dressman, Heather; Go, Alan S.; He, Jiang; Lash, James P.; Kusek, John W.; Raj, Dominic S.

    2014-01-01

    Background Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD). Methods We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium HumanMethylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate. Results The mean eGFR slope was 2.2 (1.4) and −5.1 (1.2) mL/min/1.73 m2 in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E−05 to 9.5E−05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E−03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD. Conclusions Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD. PMID:24516231

  4. Metformin-associated lactic acidosis in a patient with normal kidney function.

    PubMed

    van Sloten, T T; Pijpers, E; Stehouwer, C D A; Brouwers, M C G J

    2012-06-01

    The existence of metformin-induced lactic acidosis has been questioned, in particular in the absence of specific risk factors such as impaired renal function. This report describes the presence of lactic acidosis in a patient with normal kidney function and normal doses of metformin. Subsequent positive rechallenge with metformin confirms causality.

  5. Polygenic overlap between kidney function and large artery atherosclerotic stroke.

    PubMed

    Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Stephen; Maguire, Jane; Koblar, Simon A; Sturm, Jonathan; Hankey, Graeme J; Oldmeadow, Christopher; McEvoy, Mark; Sudlow, Cathie; Rothwell, Peter M; Coresh, Josef; Hamet, Pavel; Tremblay, Johanne; Turner, Stephen T; de Andrade, Mariza; Rao, Madhumathi; Schmidt, Reinhold; Crick, Peter A; Robino, Antonietta; Peralta, Carmen A; Jukema, J Wouter; Mitchell, Paul; Rosas, Sylvia E; Wang, Jie Jin; Scott, Rodney J; Dichgans, Martin; Mitchell, Braxton D; Kao, W H Linda; Fox, Caroline S; Levi, Christopher; Attia, John; Markus, Hugh S

    2014-12-01

    Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes. Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73 998), eGFR using cystatin C (eGFRcys: n=22 937), and urinary albumin to creatinine ratio (n=31 580). For each, single nucleotide polymorphisms passing 10 P value thresholds were used to form profile scores in 4561 IS cases and 7094 controls from the United Kingdom, Germany, and Australia. Scores were tested for association with IS and its 3 aetiological subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease. Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of large artery atherosclerosis, with 5 scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher urinary albumin to creatinine ratio, of which 3 associated with large artery atherosclerosis (peak P=0.01) and all showed the expected directional association. One urinary albumin to creatinine ratio-based score also associated with small vessel disease (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02). This study suggests possible polygenic correlation between renal dysfunction and IS. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders seems merited. © 2014 American Heart Association, Inc.

  6. Polygenic overlap between kidney function and large artery atherosclerotic stroke

    PubMed Central

    Holliday, Elizabeth G.; Traylor, Matthew; Malik, Rainer; Bevan, Stephen; Maguire, Jane; Koblar, Simon A.; Sturm, Jonathan; Hankey, Graeme J.; Oldmeadow, Christopher; McEvoy, Mark; Sudlow, Cathie; Rothwell, Peter M.; Coresh, Josef; Hamet, Pavel; Tremblay, Johanne; Turner, Stephen T.; de Andrade, Mariza; Rao, Madhumathi; Schmidt, Reinhold; Crick, Peter A.; Robino, Antonietta; Peralta, Carmen A.; Jukema, J. Wouter; Mitchell, Paul; Rosas, Sylvia E.; Wang, Jie Jin; Scott, Rodney J.; Dichgans, Martin; Mitchell, Braxton D.; Linda Kao, W. H.; Fox, Caroline S.; Levi, Christopher; Attia, John; Markus, Hugh S

    2014-01-01

    Background and Purpose Epidemiological studies show strong associations between kidney dysfunction and risk of ischaemic stroke, the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability due to a common polygenic basis and whether this differed for ischaemic stroke subtypes. Methods Polygenic models were derived using GWAS meta-analysis results for three kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: N=73,998), eGFR using cystatin C (eGFRcys: N=22,937) and urinary albumin to creatinine ratio (UACR: N=31,580). For each, SNPs passing ten P-value thresholds were used to form profile scores in 4,561 ischaemic stroke cases and 7,094 controls from the UK, Germany and Australia. Scores were tested for association with ischaemic stroke and its three aetiological subtypes: large artery atherosclerosis (LAA), cardioembolism (CE) and small vessel disease (SVD). Results Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of LAA, with five scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher UACR, of which three associated with LAA (peak P=0.01) and all showed the expected directional association. One UACR-based score also associated with SVD (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02). Conclusions This study suggests possible polygenic correlation between renal dysfunction and ischaemic stroke. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders appears merited. PMID:25352485

  7. Association Between Age-Related Decline of Kidney Function and Plasma Malondialdehyde

    PubMed Central

    Chen, Yaqin; Hu, Hui; Liu, Li; Hu, Xiaofei; Wang, Jun; Shi, Wang; Yin, Dazhong

    2012-01-01

    Abstract Oxidative stress is a key factor linked renal function decline with age. However, there is still no large cohort study exploring the potential role of oxidative stress in mild insufficiency of kidney function (MIKF) and chronic kidney disease (CKD) after adjusting for confounding factors. This study tested the hypothesis that oxidative stress, indicated by plasma malondialdehyde (MDA), is associated with the prevalence of MIKF and CKD after controlling the effects of confounding factors. Plasma levels of MDA and serum levels of fasting glucose, cholesterol, triglycerides, creatinine, alanine aminotransferase, and aspartate aminotransferase were analyzed from 2,169 Chinese Han adults. A questionnaire and physical examination were performed to identify and suspect risk factors of renal function decline with age. Kidney function, as indicated by estimated glomerular filtration rate, showed a significant decline with age in both male and female. Although the association between age and plasma MDA levels was nonlinear, MDA was negatively related to kidney function. The multivariate-adjusted odds ratios showed that plasma MDA had a significantly graded relation to the prevalence of MIKF and CKD with or without adjustment for covariates. By comparison with the lowest quartile, individuals with the highest quartile of MDA level had a 99% and 223% increased risk of developing MIKF and CKD, respectively. Further results from multiinteraction analysis demonstrated that plasma MDA may be the mediator linking different covariates with renal function decline. The most striking finding of this study was that oxidative stress, as indicated by plasma MDA levels, is associated with the prevalence of MIKF and/or CKD. Although imposing an increasing burden on the kidney and/or promoting a cyclical process of oxidative stress in the body, high levels of MDA in plasma may link the decline of kidney function with age. PMID:22530729

  8. The impact of anaemia and kidney function in congestive heart failure and preserved systolic function.

    PubMed

    Philipp, Sebastian; Ollmann, Henrike; Schink, Tania; Dietz, Rainer; Luft, Friedrich C; Willenbrock, Roland

    2005-05-01

    The importance of anaemia in chronic heart failure was highlighted recently by different cohort studies. The aim of this study was to assess the prevalence of anaemia and its relationship to renal function, left ventricular function and symptoms of heart failure. We surveyed cases of patients admitted to the Department of Cardiology during 22 consecutive months. Laboratory measurements, blood pressure and echocardiographic parameters were obtained with standardized methods. Out of a total number of 2941 patients, 238 patients (8.1%) had haemoglobin values <11 g/dl. There was a positive association of anaemia with the symptoms of heart failure with a lowering of the median haemoglobin from 14.2 g/dl [New York Heart Association (NYHA) I] to 12.9 g/dl (NYHA IV, P<0.001). Interestingly, anaemia was not associated with left ventricular function or any left ventricular parameters. Symptoms of heart failure, however, were associated with kidney function. The estimated glomerular filtration rate (GFR) was 82 ml/min at NYHA I and 59 ml/min at NYHA IV, P<0.05. There was an association between impaired renal function and haemoglobin values. Haemoglobin was 14.2 g/dl in the group with normal renal function and 11.1 g/dl in the group with a GFR <25 ml/min (P<0.001). Even in patients with normal renal function (878 patients, GFR >85 ml/min), we still found an association of anaemia with the symptoms of heart failure. Haemoglobin was 14.5 g/dl at NYHA I and 13.4 g/dl at NYHA IV, P<0.0001. Anaemia is found in 8.1% of patients admitted to cardiology service. Anaemia was clearly associated with symptoms of congestive heart failure even in patients with normal renal function. Anaemia was not associated with left ventricular function.

  9. Functional Status, Time to Transplantation, and Survival Benefit of Kidney Transplantation Among Wait-Listed Candidates

    PubMed Central

    Reese, Peter P.; Shults, Justine; Bloom, Roy D.; Mussell, Adam; Harhay, Meera N.; Abt, Peter; Levine, Matthew; Johansen, Kirsten L.; Karlawish, Jason T.; Feldman, Harold I.

    2015-01-01

    Background In the context of an aging end-stage renal disease population with multiple comorbidities, transplantation professionals face challenges in evaluating the global health of patients awaiting kidney transplantation. Functional status might be useful for identifying which patients will derive a survival benefit from transplantation versus dialysis. Study Design Retrospective cohort study of wait-listed patients using data on functional status from a national dialysis provider linked to United Network for Organ Sharing registry data. Setting & Participants Adult kidney transplant candidates added to the waiting list between the years 2000 and 2006. Predictor Physical function scale of the Medical Outcomes Study 36-Item Short Form Healthy Survey, analyzed as a time-varying covariate. Outcomes Kidney transplantation; Survival benefit of transplantation versus remaining wait-listed. Measurements We used multivariable Cox regression to assess the association between physical function with study outcomes. In survival benefit analyses, transplant status was modeled as a time-varying covariate. Results The cohort comprised 19,242 kidney transplant candidates (median age, 51 years; 36% black race) receiving maintenance dialysis. Candidates in the lowest baseline physical function quartile were more likely to be inactivated (adjusted HR vs. highest quartile, 1.30; 95% CI, 1.21-1.39) and less likely to undergo transplantation (adjusted HR vs. highest quartile, 0.64; 95% CI, 0.61-0.68). After transplantation, worse physical function was associated with shorter 3-year survival (84% vs. 92% for the lowest vs. highest function quartiles). However, compared to dialysis, transplantation was associated with a statistically significant survival benefit by 9 months for patients in every function quartile. Limitations Functional status is self-reported. Conclusions Even patients with low function appear to live longer with kidney transplantation versus dialysis. For waitlisted

  10. Allograft tolerance in pigs after fractionated lymphoid irradiation. II. Kidney graft after conventional total lymphoid irradiation and bone marrow cell grafting

    SciTech Connect

    Fradelizi, D.; Mahouy, G.; de Riberolles, C.; Lecompte, Y.; Alhomme, P.; Douard, M.C.; Chotin, G.; Martelli, H.; Daburon, F.; Vaiman, M.

    1981-05-01

    Experiments with pigs have been performed in order to establish bone marrow chimerism and kidney graft tolerance between SLA genotyped semi-incompatible animals. Recipients were conditioned by means of conventional fractionated total lymphoid irradiation (TLI) delivered by a vertical cobalt source. The principal lymphoid regions of the pig, including thymus and spleen, were submitted to irradiation. Two protocols were tested: A = 250 cGy four times a week x 13 times (TLI) (two animals) and B = 350 cGy three times a week x 8 times (TLI) (four animals). Bone marrow cells were injected 24 h after the last irradiation. One day later, bilateral nephrectomy and the graft of one kidney from the bone marrow cell donor were performed simultaneously. Results convinced us that application of the TLI protocol to humans is not yet practicable and that further experimental work is needed.

  11. Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Driver, Todd H.; Shlipak, Michael G.; Katz, Ronit; Goldenstein, Leonard; Sarnak, Mark J.; Hoofnagle, Andrew N.; Siscovick, David S.; Kestenbaum, Bryan; de Boer, Ian H.; Ix, Joachim H.

    2014-01-01

    Background Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Study Design Retrospective cohort study. Setting & Participants 6380 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m2 using the CKD-EPI (CKD Epidemiology Collaboration) creatinine–cystatin C equation. Predictors Serum bicarbonate concentrations. Outcomes Rapid kidney function decline (eGFR decline >5% per year) and incident reduced eGFR (eGFR<60 mL/min/1.73 m2 with minimum rate of eGFR loss of 1 mL/min/1.73 m2 per year). Results The average bicarbonate concentration was 23.2 ± 1.8 mEq/L. 1730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%–20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03–1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate <21mEq/L relative to 23–24 mEq/L was 1.35 (95% CI, 1.05–1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83–1.62) for incident reduced eGFR. Limitations Etiology of metabolic acidosis cannot be determined in this study. Conclusions Lower serum bicarbonate concentrations are independently associated with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with a baseline eGFR >60 mL/min/1.73 m2. If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria, or may have a causal role

  12. Changes in bone matrix mineralization after growth hormone treatment in children and adolescents with chronic kidney failure treated by dialysis: a paired biopsy study.

    PubMed

    Nawrot-Wawrzyniak, Kamilla; Misof, Barbara M; Roschger, Paul; Pańczyk-Tomaszewska, Małgorzata; Ziółkowska, Helena; Klaushofer, Klaus; Fratzl-Zelman, Nadja

    2013-05-01

    Patients with chronic kidney disease (CKD) develop renal osteodystrophy with alterations in bone turnover, mineralization, and volume (TMV). A specific skeletal complication in children is growth impairment, which currently is treated by recombinant human growth hormone (rhGH). The effects on bone material properties are poorly understood. This study assesses the effects of rhGH treatment on bone matrix mineralization. Observational study. 18 short children and adolescents (aged 3.6-16 years) with CKD on dialysis therapy. rhGH treatment for 1 year. Tetracycline-labeled bone biopsy classified according to the TMV system. Bone mineralization density distribution (BMDD) was evaluated by quantitative backscattered electron imaging in trabecular and cortical compartments. Additional data for patients' height and biochemical bone serum parameters were obtained. Prior to rhGH treatment, our cohort showed low bone turnover and high mineralization densities versus reference data: Ca(mean) (weighted mean calcium content) in cancellous bone, +3.3% (P = 0.04); Ca(mean) in cortical bone, +6.7% (P < 0.001); Ca(peak) (mode of the BMDD) in cancellous bone, +5.0% (P < 0.001); Ca(peak) in cortical bone, +8.2% (P < 0.001); Ca(width) (heterogeneity in mineralization), no significant difference for cancellous (P = 0.2) and cortical (P = 0.1) bone; Ca(high) (portion of fully mineralized bone) in cancellous bone, 5-fold greater (P < 0.001); Ca(high) in cortical bone, 14-fold greater (P < 0.001); Ca(low) (portion of low mineralized bone) in cancellous bone, +23.9% (P = 0.02); Ca(low) in cortical bone, -22.2% (P = 0.05). After rhGH treatment, height increased by 9.1 cm (P < 0.001) and bone turnover indices to normal values or beyond. Matrix mineralization was lesser and more heterogeneous compared to baseline: Ca(width) for cancellous bone, +15.3% (P < 0.001); Ca(width) for cortical bone, +34.1% (P < 0.001). Ca(mean), Ca(peak), and Ca(high) for cancellous bone and Ca(mean) and Ca(peak) for

  13. Subclinical cardiac abnormalities and kidney function decline: the multi-ethnic study of atherosclerosis.

    PubMed

    Park, Meyeon; Shlipak, Michael G; Katz, Ronit; Agarwal, Subhashish; Ix, Joachim H; Hsu, Chi-Yuan; Peralta, Carmen A

    2012-07-01

    Clinical heart failure (HF) is associated with CKD and faster rates of kidney function decline. Whether subclinical abnormalities of cardiac structure are associated with faster kidney function decline is not known. The association between cardiac concentricity and kidney function decline was evaluated. This is a longitudinal study of 3866 individuals from the Multi-Ethnic Study of Atherosclerosis (2000-2007) who were free of clinical cardiovascular disease, with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) at baseline and 5 years of follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by magnetic resonance imaging and evaluated as a continuous measurement and in quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The association of concentricity with annual eGFR decline, incident CKD, and rapid kidney function decline (>5% per year) was investigated using linear mixed models as well as Poisson and logistic regression, respectively. Analyses adjusted for demographics, BP, diabetes, and inflammatory markers. Median decline was -0.8 (interquartile range, -3.1, -0.5) by eGFRcr. Compared with the lowest quartile of concentricity, persons in the highest quartile had an additional 21% (9%-32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also associated with incident CKD and with rapid kidney function decline after adjustment. Subclinical abnormalities in cardiac structure are associated with longitudinal kidney function decline independent of diabetes and hypertension. Future studies should examine mechanisms to explain these associations.

  14. Subclinical Cardiac Abnormalities and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Shlipak, Michael G.; Katz, Ronit; Agarwal, Subhashish; Ix, Joachim H.; Hsu, Chi-yuan; Peralta, Carmen A.

    2012-01-01

    Summary Background and objectives Clinical heart failure (HF) is associated with CKD and faster rates of kidney function decline. Whether subclinical abnormalities of cardiac structure are associated with faster kidney function decline is not known. The association between cardiac concentricity and kidney function decline was evaluated. Design, setting, participants, & measurements This is a longitudinal study of 3866 individuals from the Multi-Ethnic Study of Atherosclerosis (2000–2007) who were free of clinical cardiovascular disease, with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m2 at baseline and 5 years of follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by magnetic resonance imaging and evaluated as a continuous measurement and in quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The association of concentricity with annual eGFR decline, incident CKD, and rapid kidney function decline (>5% per year) was investigated using linear mixed models as well as Poisson and logistic regression, respectively. Analyses adjusted for demographics, BP, diabetes, and inflammatory markers. Results Median decline was −0.8 (interquartile range, −3.1, −0.5) by eGFRcr. Compared with the lowest quartile of concentricity, persons in the highest quartile had an additional 21% (9%–32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also associated with incident CKD and with rapid kidney function decline after adjustment. Conclusions Subclinical abnormalities in cardiac structure are associated with longitudinal kidney function decline independent of diabetes and hypertension. Future studies should examine mechanisms to explain these associations. PMID:22580783

  15. Analysis of nephron composition and function in the adult zebrafish kidney.

    PubMed

    McCampbell, Kristen K; Springer, Kristin N; Wingert, Rebecca A

    2014-08-09

    The zebrafish model has emerged as a relevant system to study kidney development, regeneration and disease. Both the embryonic and adult zebrafish kidneys are composed of functional units known as nephrons, which are highly conserved with other vertebrates, including mammals. Research in zebrafish has recently demonstrated that two distinctive phenomena transpire after adult nephrons incur damage: first, there is robust regeneration within existing nephrons that replaces the destroyed tubule epithelial cells; second, entirely new nephrons are produced from renal progenitors in a process known as neonephrogenesis. In contrast, humans and other mammals seem to have only a limited ability for nephron epithelial regeneration. To date, the mechanisms responsible for these kidney regeneration phenomena remain poorly understood. Since adult zebrafish kidneys undergo both nephron epithelial regeneration and neonephrogenesis, they provide an outstanding experimental paradigm to study these events. Further, there is a wide range of genetic and pharmacological tools available in the zebrafish model that can be used to delineate the cellular and molecular mechanisms that regulate renal regeneration. One essential aspect of such research is the evaluation of nephron structure and function. This protocol describes a set of labeling techniques that can be used to gauge renal composition and test nephron functionality in the adult zebrafish kidney. Thus, these methods are widely applicable to the future phenotypic characterization of adult zebrafish kidney injury paradigms, which include but are not limited to, nephrotoxicant exposure regimes or genetic methods of targeted cell death such as the nitroreductase mediated cell ablation technique. Further, these methods could be used to study genetic perturbations in adult kidney formation and could also be applied to assess renal status during chronic disease modeling.

  16. Analysis of Nephron Composition and Function in the Adult Zebrafish Kidney

    PubMed Central

    McCampbell, Kristen K.; Springer, Kristin N.; Wingert, Rebecca A.

    2014-01-01

    The zebrafish model has emerged as a relevant system to study kidney development, regeneration and disease. Both the embryonic and adult zebrafish kidneys are composed of functional units known as nephrons, which are highly conserved with other vertebrates, including mammals. Research in zebrafish has recently demonstrated that two distinctive phenomena transpire after adult nephrons incur damage: first, there is robust regeneration within existing nephrons that replaces the destroyed tubule epithelial cells; second, entirely new nephrons are produced from renal progenitors in a process known as neonephrogenesis. In contrast, humans and other mammals seem to have only a limited ability for nephron epithelial regeneration. To date, the mechanisms responsible for these kidney regeneration phenomena remain poorly understood. Since adult zebrafish kidneys undergo both nephron epithelial regeneration and neonephrogenesis, they provide an outstanding experimental paradigm to study these events. Further, there is a wide range of genetic and pharmacological tools available in the zebrafish model that can be used to delineate the cellular and molecular mechanisms that regulate renal regeneration. One essential aspect of such research is the evaluation of nephron structure and function. This protocol describes a set of labeling techniques that can be used to gauge renal composition and test nephron functionality in the adult zebrafish kidney. Thus, these methods are widely applicable to the future phenotypic characterization of adult zebrafish kidney injury paradigms, which include but are not limited to, nephrotoxicant exposure regimes or genetic methods of targeted cell death such as the nitroreductase mediated cell ablation technique. Further, these methods could be used to study genetic perturbations in adult kidney formation and could also be applied to assess renal status during chronic disease modeling. PMID:25145398

  17. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

    PubMed Central

    Ali, Quaisar

    2016-01-01

    We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions. PMID:27528887

  18. Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.

    PubMed

    Kelpke, Stacey S; Chen, Bo; Bradley, Kelley M; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A; Crossman, David K; Bray, Molly S; Eckhoff, Devin E; Agarwal, Anupam; Patel, Rakesh P

    2012-08-01

    Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

  19. Pre-clinical functional Magnetic Resonance Imaging Part I: The kidney.

    PubMed

    Zöllner, Frank G; Kalayciyan, Raffi; Chacón-Caldera, Jorge; Zimmer, Fabian; Schad, Lothar R

    2014-12-01

    The prevalence of chronic kidney disease (CKD) is increasing worldwide. In Europe alone, at least 8% of the population currently has some degree of CKD. CKD is associated with serious comorbidity, reduced life expectancy, and high economic costs; hence, the early detection and adequate treatment of kidney disease is important. Pre-clinical research can not only give insights into the mechanisms of the various kidney diseases but it also allows for investigating the outcome of new drugs developed to treat kidney disease. Functional magnetic resonance imaging provides non-invasive access to tissue and organ function in animal models. Advantages over classical animal research approaches are numerous: the same animal might be repeatedly imaged to investigate a progress or a treatment of disease over time. This has also a direct impact on animal welfare and the refinement of classical animal experiments as the number of animals in the studies might be reduced. In this paper, we review current state of the art in functional magnetic resonance imaging with a focus on pre-clinical kidney imaging. Copyright © 2014. Published by Elsevier GmbH.

  20. Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study.

    PubMed

    Ballew, Shoshana H; Chen, Yan; Daya, Natalie R; Godino, Job G; Windham, B Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E

    2017-02-01

    Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Observational study. 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C level (eGFRcys) and urine albumin-creatinine ratio. Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). 341 (7%) participants were classified as frail, 1,475 (30%) had eGFRcr<60mL/min/1.73m(2), 2,480 (50%) had eGFRcys<60mL/min/1.73m(2), and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys<60mL/min/1.73m(2) were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and albumin-creatinine ratio. Frail individuals with eGFRcr of 60 to <75mL/min/1.73m(2) were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m(2)). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Cross-sectional study design. Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in chronic kidney disease

  1. Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease.

    PubMed

    Ko, Yi-An; Yi, Huiguang; Qiu, Chengxiang; Huang, Shizheng; Park, Jihwan; Ledo, Nora; Köttgen, Anna; Li, Hongzhe; Rader, Daniel J; Pack, Michael A; Brown, Christopher D; Susztak, Katalin

    2017-06-01

    Chronic kidney disease (CKD) is a complex gene-environmental disease affecting close to 10% of the US population. Genome-wide association studies (GWASs) have identified sequence variants, localized to non-coding genomic regions, associated with kidney function. Despite these robust observations, the mechanism by which variants lead to CKD remains a critical unanswered question. Expression quantitative trait loci (eQTL) analysis is a method to identify genetic variation associated with gene expression changes in specific tissue types. We hypothesized that an integrative analysis combining CKD GWAS and kidney eQTL results can identify candidate genes for CKD. We performed eQTL analysis by correlating genotype with RNA-seq-based gene expression levels in 96 human kidney samples. Applying stringent statistical criteria, we detected 1,886 genes whose expression differs with the sequence variants. Using direct overlap and Bayesian methods, we identified new potential target genes for CKD. With respect to one of the target genes, lysosomal beta A mannosidase (MANBA), we observed that genetic variants associated with MANBA expression in the kidney showed statistically significant colocalization with variants identified in CKD GWASs, indicating that MANBA is a potential target gene for CKD. The expression of MANBA was significantly lower in kidneys of subjects with risk alleles. Suppressing manba expression in zebrafish resulted in renal tubule defects and pericardial edema, phenotypes typically induced by kidney dysfunction. Our analysis shows that gene-expression changes driven by genetic variation in the kidney can highlight potential new target genes for CKD development. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  2. Construction of kidney phantom model with acoustic shadow by rib bones and respiratory organ motion

    NASA Astrophysics Data System (ADS)

    Lee, Dongjun; Koizumi, Norihiro; Tsukihara, Hiroyuki; Azuma, Takashi; Nomiya, Akira; Yoshinaka, Kiyoshi; Sugita, Naohiko; Homma, Yukio; Matsumoto, Yoichiro; Mitsuishi, Mamoru

    2017-03-01

    We have been studying the Non-Invasive Ultrasound Theragnostic System (NIUTS), which tracks and follows the affected area while irradiating High Intensity Focused Ultrasound (HIFU). In this report, we propose a phantom model that includes rib bones and respiratory motion.

  3. A case report of disabling bone pain after long-term kidney transplantation.

    PubMed

    Myint, T M M; Vucak-Dzumhur, M; Ebeling, P R; Elder, G J

    2014-02-01

    A 77-year-old man, who received a renal transplant 13 years before for IgA glomerulonephritis, was referred after he developed bilateral mid-tibial aching pain that did not improve with simple analgesia. He had recently been changed from low-dose cyclosporine to tacrolimus, but the pain did not improve when this was reversed. He had a history of focal prostatic adenocarcinoma, cryptococcal lung infection, osteoporosis treated with alendronate for 2 years and multiple squamous cell carcinomas, including one requiring left neck dissection and radiotherapy. Upon physical examination, he had gouty tophi and marked bilateral tibial tenderness but had no other clinical findings. Laboratory investigations included an elevated intact parathyroid hormone value of 7.9 pmol/L (1.6 to 6.9), bone specific alkaline phosphatase of 22 µg/L (3.7 to 20.9), urinary deoxypyridinoline/creatinine ratio of 7.2 nmol/mmol (2.5 to 5.4) and C-reactive protein. Chest X-ray and tibial X-rays were normal, but there was marrow oedema and a prominent periosteal reaction on magnetic resonance imaging. A radionuclide bone scan showed increased symmetrical, linear uptake in both tibiae and the left femur, and uptake was also noted in both clinically asymptomatic humeri. Tibial bone biopsy disclosed small deposits of poorly differentiated metastatic cancer and a follow-up chest CT revealed a lung lesion. It was concluded that the bone pain and periostitis was caused by primary lung cancer with metastatic disease to bone, and an associated hypertrophic osteoarthropathy.

  4. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure.

    PubMed

    Boon, Ai-Ching; Lam, Alfred K; Gopalan, Vinod; Benzie, Iris F; Briskey, David; Coombes, Jeff S; Fassett, Robert G; Bulmer, Andrew C

    2015-10-26

    Mildly elevated bilirubin is associated with a reduction in the presence and progression of chronic kidney disease and related mortality, which may be attributed to bilirubin's antioxidant properties. This study investigated whether endogenously elevated bilirubin would protect against adenine-induced kidney damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals were orally administered adenine or methylcellulose solvent (vehicle) daily for 10 days and were then monitored for 28 days. Serum and urine were assessed throughout the protocol for parameters of kidney function and antioxidant/oxidative stress status and kidneys were harvested for histological examination upon completion of the study. Adenine-treated animals experienced weight-loss, polyuria and polydipsia; however, these effects were significantly attenuated in adenine-treated Gunn rats. No difference in the presence of dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane concentrations were significantly decreased in Gunn rats versus controls, with no change in urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine or kidney tissue F2-isoprostane concentrations. These data indicated that endogenously elevated bilirubin specifically protects from systemic oxidative stress in the vascular compartment. These data may help to clarify the protective relationship between bilirubin, kidney function and cardiovascular mortality in clinical investigations.

  5. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure

    PubMed Central

    Boon, Ai-Ching; Lam, Alfred K.; Gopalan, Vinod; Benzie, Iris F.; Briskey, David; Coombes, Jeff S.; Fassett, Robert G.; Bulmer, Andrew C.

    2015-01-01

    Mildly elevated bilirubin is associated with a reduction in the presence and progression of chronic kidney disease and related mortality, which may be attributed to bilirubin’s antioxidant properties. This study investigated whether endogenously elevated bilirubin would protect against adenine-induced kidney damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals were orally administered adenine or methylcellulose solvent (vehicle) daily for 10 days and were then monitored for 28 days. Serum and urine were assessed throughout the protocol for parameters of kidney function and antioxidant/oxidative stress status and kidneys were harvested for histological examination upon completion of the study. Adenine-treated animals experienced weight-loss, polyuria and polydipsia; however, these effects were significantly attenuated in adenine-treated Gunn rats. No difference in the presence of dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane concentrations were significantly decreased in Gunn rats versus controls, with no change in urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine or kidney tissue F2-isoprostane concentrations. These data indicated that endogenously elevated bilirubin specifically protects from systemic oxidative stress in the vascular compartment. These data may help to clarify the protective relationship between bilirubin, kidney function and cardiovascular mortality in clinical investigations. PMID:26498893

  6. Adverse mandibular bone effects associated with kidney disease are only partially corrected with bisphosphonate and/or calcium treatment.

    PubMed

    Allen, Matthew R; Chen, Neal X; Gattone, Vincent H; Moe, Sharon M

    2013-01-01

    Patients with chronic kidney disease (CKD) have a high prevalence of periodontal disease that may predispose to tooth loss and inflammation. The goal of this study was to test the hypotheses that a genetic rat model of progressive CKD would exhibit altered oral bone properties and that treatment with either bisphosphonates or calcium could attenuate these adverse changes. At 25 weeks of age, rats were treated with zoledronate (ZOL), calcium gluconate, or their combination for 5 or 10 weeks. Mandible bone properties were assessed using micro-computed tomography to determine bone volume (BV/TV) and cementum-enamel junction to alveolar crest distance (CEJ-AC). Untreated CKD animals had significantly lower BV/TV at both 30 (-5%) and 35 (-14%) weeks of age and higher CEJ-AC (+27 and 29%) compared to normal animals. CKD animals had a significantly higher parathyroid hormone (PTH) compared to normal animals, yet similar levels of C-reactive protein (CRP). ZOL treatment normalized BV/TV over the first 5 weeks but this benefit was lost by 10 weeks. Calcium treatment, alone or in combination with ZOL, was effective in normalizing BV/TV at both time points. Neither ZOL nor calcium was able to correct the higher CEJ-AC caused by CKD. Calcium, but not ZOL, significantly reduced serum PTH, while neither treatment affected CRP. (i) This progressive animal model of CKD shows a clear mandibular skeletal phenotype consistent with periodontitis, (ii) the periodontitis is not associated with systemic inflammation as measured by CRP, and (iii) reducing PTH has positive effects on the mandible phenotype. © 2013 S. Karger AG, Basel.

  7. Serum albumin and kidney function decline in HIV-infected women.

    PubMed

    Lang, Joshua; Scherzer, Rebecca; Tien, Phyllis C; Parikh, Chirag R; Anastos, Kathryn; Estrella, Michelle M; Abraham, Alison G; Sharma, Anjali; Cohen, Mardge H; Butch, Anthony W; Nowicki, Marek; Grunfeld, Carl; Shlipak, Michael G

    2014-10-01

    Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in human immunodeficiency virus (HIV)-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women. Retrospective cohort analysis. Study participants were recruited from the Women's Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and 2 follow-up measurements over an average of 8 years. The primary predictor was serum albumin concentration. We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR). Kidney function decline was determined by cystatin C-based (eGFR(cys)) and creatinine-based eGFR (eGFR(cr)) at baseline and follow-up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression. After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFR(cys) (P < 0.001), which was attenuated only slightly to 0.55 mL/min/1.73 m(2) after adjustment for albuminuria. Results were similar whether using eGFR(cys) or eGFR(cr). In adjusted analyses, each 0.5-g/dL lower baseline serum albumin level was associated with a 1.71-fold greater risk of rapid kidney function decline (P < 0.001) and a 1.72-fold greater risk of incident reduced eGFR (P < 0.001). The cohort is composed of only female participants from urban communities within the United States. Lower serum albumin levels were associated strongly with kidney function decline and incident reduced eGFRs in HIV-infected women independent of HIV disease status, body mass index, and albuminuria. Published

  8. Association of visceral and subcutaneous adiposity with kidney function.

    PubMed

    Young, Jill A; Hwang, Shih-Jen; Sarnak, Mark J; Hoffmann, Udo; Massaro, Joseph M; Levy, Daniel; Benjamin, Emelia J; Larson, Martin G; Vasan, Ramachandran S; O'Donnell, Christopher J; Fox, Caroline S

    2008-11-01

    Obesity is a risk factor for incident chronic kidney disease (CKD). Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer differential metabolic risk profiles. The relations of VAT and SAT were analyzed with CKD as estimated by creatinine- and cystatin-based estimating equations. Participants from the Framingham Offspring Study who underwent abdominal computed tomography for VAT and SAT quantification were included (n = 1299; 53% women; mean age 60 yr). CKD was defined as estimated GFR <60 ml/min per 1.73 m(2), as estimated using creatinine (n = 89) in the Modification of Diet in Renal Disease (MDRD) formula or by cystatin C (n = 136). Regression models evaluated the cross-sectional relations between VAT and SAT with CKD and cystatin C, with age and gender adjustment and cardiovascular risk factor adjustment. Neither VAT nor SAT was associated with CKD as estimated by the MDRD equation. In contrast, both VAT and SAT were associated with CKD when defined using cystatin-based equations. The estimated decrease in estimated GFR by cystatin C per 1-SD increase of VAT was 1.9 ml/min per 1.73 m(2) and for SAT was 2.6 ml/min per 1.73 m(2) in a multivariable-adjusted model. VAT and SAT were associated with CKD when defined using cystatin C estimating equations but not when using a creatinine-based estimating equation. Mechanisms linking adipose tissue to cystatin C warrant further research.

  9. Generation of Functional Kidney Organoids In Vivo Starting from a Single-Cell Suspension.

    PubMed

    Benedetti, Valentina; Brizi, Valerio; Xinaris, Christodoulos

    2016-08-19

    Novel methods in developmental biology and stem cell research have made it possible to generate complex kidney tissues in vitro that resemble whole organs and are termed organoids. In this chapter we describe a technique using suspensions of fully dissociated mouse kidney cells to yield organoids that can become vascularized in vivo and mature and display physiological functions. This system can be used to produce fine-grained human-mouse chimeric organoids in which the renal differentiation potential of human cells can be assessed. It can also be an excellent method for growing chimeric organoids in vivo using human stem cells, which can differentiate into specialized kidney cells and exert nephron-specific functions. We provide detailed methods, a brief discussion of critical points, and describe some successfully implemented examples of the system.

  10. [Functional activity of bone marrow-derived peptides (myelopeptides)].

    PubMed

    Mikhaĭlova, A A; Petrov, R V

    2009-12-01

    The review describes structure and functions of bone marrow-derived peptides (myelopeptides). The final biological effects of these endogenous bioregulators (antitumor, antiviral, anti-infectious, antileukemia etc.) are due to their immunocorrecting and differentiating activity. Myelopeptides are the integral parts of the immune homeostasis maintenance system. Nowadays, medical preparations with no side effects and natural mechanisms of action are being developed on the basis of synthesized myelopeptides.

  11. Molecular and functional characterization of human bone marrow adipocytes.

    PubMed

    Poloni, Antonella; Maurizi, Giulia; Serrani, Federica; Mancini, Stefania; Zingaretti, Maria Cristina; Frontini, Andrea; Cinti, Saverio; Olivieri, Attilio; Leoni, Pietro

    2013-06-01

    Adipocytes are a cell population largely located in the human bone marrow cavity. In this specific microenvironment where adipocytes can interact with a variety of different cells, the role of fat is mainly unknown. To our knowledge, this report is the first to characterize mature adipocytes isolated from human bone marrow (BM-A) molecularly and functionally to better understand their roles into the hematopoietic microenvironment. Healthy BM-A were isolated after collagenase digestion and filtration. We studied the morphology of BM-A, their gene expression and immunophenotypic profile and their functional ability in the hematopoietic microenvironment, comparing them with adipocytes derived from adipose tissue (AT-A). BM-A showed a unilocular lipid morphology similar to AT-A and did not lose their morphology in culture; they showed a comparable pattern of stem cell-surface antigens to AT-A. In line with these observations, molecular data showed that BM-A expressed some embryonic stem cells genes, such as Oct4, KLf4, c-myc, Gata4, Tbx1, and Sox17, whereas they did not express the stem cell markers Sox2 and Nanog. Moreover, BM-A had long telomeres that were similar to bone marrow mesenchymal stem cells. Notably, BM-A supported the survival and differentiation of hematopoietic stem cells in long-term cultures. These results showed that BM-A are stromal cells with a gene expression pattern that distinguished them from AT-A. BM-A showed stem cell properties through their hematopoietic supporting function, which was certainly linked to their role in the maintenance of the bone marrow microenvironment. Depending on specific demands, BM-A may acquire different functions based on their local environment. Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  12. Augmented mandibular bone structurally adapts to functional loading.

    PubMed

    Verhoeven, J W; Ruijter, J M; Koole, R; de Putter, C; Terlou, M; Cune, M S

    2013-12-01

    Long-term changes in trabecular bone structure during the 10 years following onlay grafting with simultaneous mandibular implant placement were studied. Extraoral radiographs of both mandibular sides in eight patients were taken regularly. Bone structure was analysed using a custom-written image analysis program. Parameters studied were trabecular area and perimeter and marrow cavity area and perimeter. After skeletonisation of the trabecular network, the number of end points and branching points, skeleton length, and branch angle were determined. The observed structural changes agree with the development of a more complex and more delicate or fine osseous structure. The bone shows more trabecular branching. All changes are most pronounced in the graft spongiosa, but are also found in the graft cortex and in the original mandible. The mean trabecular branch angle becomes more horizontal. The applied technique can be used to analyse long-term changes in the architecture of bone grafts. Changes found in the graft architecture correspond to changes expected after functional adaptation to loading. Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  13. Twelve-Month Pancreas Graft Function Significantly Influences Survival Following Simultaneous Pancreas-Kidney Transplantation

    PubMed Central

    Weiss, Andrew S.; Smits, Gerard; Wiseman, Alexander C.

    2009-01-01

    Background and objectives: Simultaneous pancreas-kidney transplantation (SPK) is regarded as the treatment of choice for type 1 diabetes (T1DM) and kidney dysfunction, despite the morbidity associated with pancreas transplantation. These morbidities often influence selection of SPK versus living-donor kidney alone (LD KA) transplant. This study quantifies the impact of pancreas graft function on outcomes following SPK. Design, setting, participants, & measurements: Using the SRTR database, SPK wait-listed patients transplanted from 1997 to 2005 were evaluated and segregated as: (1) SPK recipients with functioning pancreas graft 12 mo posttransplant (SPK, P+); (2) SPK recipients with loss of pancreas graft function within 12 mo posttransplant (SPK, P-); (3) recipients of deceased donor (DD) KA; (4) recipients of LD KA. The study compared patient and kidney graft survival to 84 mo posttransplant. Results: Patient survival for SPK, P+ was significantly better than the LD KA; SPK, P-; and DD KA cohorts (88.6% versus 80.0%, 73.9% and 64.8%, respectively [P < 0.001]), a finding confirmed by multivariate analysis and not influenced by pancreas-after-kidney transplantation (PAK) rates and outcomes. Unadjusted graft survival was also highest in the SPK, P+ cohort (72.0% versus 63.6%, 59.8%, 49.7%, P = 0.015 versus LD KA). Conclusions: SPK recipients with functioning pancreas grafts have superior survival compared with LD KA and DD KA, including in the setting of PAK. Early pancreas graft failure results in kidney and patient survival rates similar to KA. These data help further clarify the decision-making of SPK versus KA transplant options for patients and providers. PMID:19406961

  14. Twelve-month pancreas graft function significantly influences survival following simultaneous pancreas-kidney transplantation.

    PubMed

    Weiss, Andrew S; Smits, Gerard; Wiseman, Alexander C

    2009-05-01

    Simultaneous pancreas-kidney transplantation (SPK) is regarded as the treatment of choice for type 1 diabetes (T1DM) and kidney dysfunction, despite the morbidity associated with pancreas transplantation. These morbidities often influence selection of SPK versus living-donor kidney alone (LD KA) transplant. This study quantifies the impact of pancreas graft function on outcomes following SPK. Using the SRTR database, SPK wait-listed patients transplanted from 1997 to 2005 were evaluated and segregated as: (1) SPK recipients with functioning pancreas graft 12 mo posttransplant (SPK, P+); (2) SPK recipients with loss of pancreas graft function within 12 mo posttransplant (SPK, P-); (3) recipients of deceased donor (DD) KA; (4) recipients of LD KA. The study compared patient and kidney graft survival to 84 mo posttransplant. Patient survival for SPK, P+ was significantly better than the LD KA; SPK, P-; and DD KA cohorts (88.6% versus 80.0%, 73.9% and 64.8%, respectively [P < 0.001]), a finding confirmed by multivariate analysis and not influenced by pancreas-after-kidney transplantation (PAK) rates and outcomes. Unadjusted graft survival was also highest in the SPK, P+ cohort (72.0% versus 63.6%, 59.8%, 49.7%, P = 0.015 versus LD KA). SPK recipients with functioning pancreas grafts have superior survival compared with LD KA and DD KA, including in the setting of PAK. Early pancreas graft failure results in kidney and patient survival rates similar to KA. These data help further clarify the decision-making of SPK versus KA transplant options for patients and providers.

  15. Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

    PubMed Central

    Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

    2013-01-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

  16. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    PubMed Central

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-01-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45–4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

  17. Common variants in Mendelian kidney disease genes and their association with renal function.

    PubMed

    Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

    2013-12-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

  18. Combined effects of fluoride and cadmium on liver and kidney function in male rats.

    PubMed

    Zhang, Junmin; Song, Jingjuan; Zhang, Jun; Chen, Xiao; Zhou, Meixia; Cheng, Guang; Xie, Xinyou

    2013-12-01

    It has been shown that cadmium and fluoride may both have adverse effects on liver and kidney functions, but most studies focus on a single agent. In this study, we observed the effects of cadmium and fluoride on liver and kidney functions using a rat model. Total of 24 Sprague-Dawley male rats were divided into four groups, one control group and three exposure groups that were given cadmium (50 mg/L) and fluoride (100 mg/L) alone or in combination via drinking water. At the 12th week, urine, blood, and kidney tissues were collected. Aspartate transaminase, alanine transaminase (ALT), urinary β2-microglobulin, and albumin were determined. Contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver and kidney homogenates were measured to evaluate oxidative stress. There was a significant increase in serum ALT and urinary β2-microglobulin of rats in exposure groups compared with control. Serum ALT and urinary β2-microglobulin of rats exposed to cadmium and fluoride in combination was significantly higher than those treated with cadmium alone and fluoride alone. SOD declined significantly and MDA increased in combination group compared with control and those treated with cadmium and fluoride alone. Cadmium and fluoride co-exposure increase the liver and kidney damage compared with that exposed to cadmium or fluoride alone.

  19. Bone mineral density and functional measures in patients with arthrogryposis.

    PubMed

    Spencer, Hillard T; Bowen, Richard E; Caputo, Kimberly; Green, Terri A; Lawrence, John F

    2010-01-01

    Patients with arthrogryposis often report decreased ambulation and physical activity. Given that skeletal mineralisation is responsive to force, we identified the need to characterize bone mineral density and functional measures in this population, and conducted a cross-sectional study to establish a reference for future investigations. Thirty consecutive patients aged 5 to 18 years with either the diagnosis of amyoplasia or nonsyndromic arthrogryposis with predominantly lower extremity involvement underwent bone densitometry testing, and lumbar spine Z-scores were calculated against an age and sex-matched control population as is customary in children. Pediatric outcomes data collection instrument (PODCI) and functional independence measure for Children (WeeFIM) assessment forms were completed. Mean Z-scores, PODCI, and WeeFIM scores were calculated. Statistical analysis was performed to compare lumbar spine Z-scores between patients divided by ambulatory status and to correlate WeeFIM and PODCI scores. Mean lumbar spine Z-score was -0.47, with 73% of Z-scores being <0. Mean Z-score among nonambulators or home ambulators was -1.05, as compared to a mean Z-score among limited and unlimited community ambulators of -0.14 with a trend toward significance (P=0.10), and a dose-response relationship between higher bone density and increasing ambulatory function. Mean WeeFIM self-care and mobility quotient scores were 67.5/100 and 70.9/100, respectively. PODCI normative scores were decreased for upper extremity (10/50), transfer/basic mobility (-17/50), and sports/physical function (4/50), but normal in pain/comfort (45/50) and happiness (49/50). A linear relationship was noted between functional ambulation level and WeeFIM quotient and PODCI normative scores. There was good correlation between WeeFIM mobility and PODCI transfers and basic mobility standardised scores (R=0.86). This is the first study to measure bone mineral density in children with arthrogryposis, and

  20. [Effects of smoking on the thyroid gland, digestive system, kidney and bone].

    PubMed

    Underner, M; Hadjadj, S; Beauchant, M; Bridoux, F; Debiais, F; Meurice, J-C

    2008-12-01

    In addition to being a major cardiovascular risk factor, smoking promotes or worsens thyroid, digestive, renal and bone diseases. Smoking is positively associated with hyperthyroidism. It is associated with Graves' disease and it especially increases the risk of the development of severe exophthalmos. In contrast, smoking might exert a protective action for thyroid carcinoma. Smoking increases the severity of hepatic lesions in patients with chronic hepatitis C. Smoking accelerates the progression of primary biliary cirrhosis and increases the risk of hepatocellular carcinoma. Smoking increases risk of both hyperplastic and adenomatous polyps. While Crohn's disease is associated with smoking, ulcerative colitis is largely a disease of non smokers. Smoking increases risk of development of both renal cell carcinoma and chronic nephropathies, particularly in types 1 and 2 diabetes. Smoking is a risk factor for decreased bone density and is associated with a significantly increased risk of fracture. Smoking is related to the development of rheumatoid arthritis and may adversely influence its severity. Smoking might be considered a risk factor for the development of several thyroid, digestive, renal and bone diseases. Consequently, smoking prevention and cessation programs must be strongly encouraged among the patients concerned.

  1. Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters.

    PubMed

    Ketteler, Markus; Block, Geoffrey A; Evenepoel, Pieter; Fukagawa, Masafumi; Herzog, Charles A; McCann, Linda; Moe, Sharon M; Shroff, Rukshana; Tonelli, Marcello A; Toussaint, Nigel D; Vervloet, Marc G; Leonard, Mary B

    2017-07-01

    The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document. Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD-mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease. Copyright © 2017 KDIGO. Published by Elsevier Inc. All rights reserved.

  2. Kidney Dysplasia

    MedlinePlus

    ... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

  3. Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities

    PubMed Central

    Xie, Hui; Wang, Zhenxing; Zhang, Liming; Lei, Qian; Zhao, Aiqi; Wang, Hongxiang; Li, Qiubai; Cao, Yilin; Jie Zhang, Wen; Chen, Zhichao

    2017-01-01

    Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering. PMID:28367979

  4. Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities.

    PubMed

    Xie, Hui; Wang, Zhenxing; Zhang, Liming; Lei, Qian; Zhao, Aiqi; Wang, Hongxiang; Li, Qiubai; Cao, Yilin; Jie Zhang, Wen; Chen, Zhichao

    2017-04-03

    Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering.

  5. The excretory system of young chickens experiencing mercury toxicity--effects on kidney development, morphology, and function.

    PubMed

    Hester, P Y; Brake, J; Sikes, C V; Thaxton, P; Pardue, S L

    1978-01-01

    Four trials were conducted to determine if toxic levels of mercury affect kidney development, morphology, and renal function. Mercury, administered via the drinking water as mercuric chloride caused a reduction in gross kidney weight, an increase in relative kidney weight and a slight but significant increase in the percentage water retained by left kidney of 6-week-old cockerels. Mercury had no effect on renal function of 6-week-old birds as indicated by the clearance of phenol red from circulation. Histological discontinuity of the kidney was extensive and evidenced by foamy cell degeneration and nuclear pyknosis. Although mercury caused gross alterations in the morphology of the kidney, normal excretory function was maintained.

  6. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2013-10-01

    CONTRACTING ORGANIZATION: University of California, Davis Davis, CA 95818 REPORT DATE: October 2013 TYPE OF REPORT: Annual PREPARED FOR...Nerve Function in Age-Related Bone Loss and Changes in 5a. CONTRACT NUMBER Bone Adaptation 5b. GRANT NUMBER W81XWH- 12-1-0377 5c...metabolism, and neuropeptide concentrations in bone compared to vehicle-injected mice (months 1-12): 1a. Institutional approval of animal use protocols

  7. Bone tumor

    MedlinePlus

    ... primary bone tumors include: Chondrosarcoma Ewing sarcoma Fibrosarcoma Osteosarcomas Cancers that most often spread to the bone are cancers of the: Breast Kidney Lung Prostate Thyroid These forms of cancer usually affect ...

  8. The kidney disease quality of life cognitive function subscale and cognitive performance maintenance hemodialysis patients

    USDA-ARS?s Scientific Manuscript database

    Background: Cognitive impairment is common but often undiagnosed in patients with end-stage renal disease, in part reflecting limited validated and easily administered tools to assess cognitive function in dialysis patients. Accordingly, we assessed the utility of the Kidney Disease Quality of Life ...

  9. Donor kidney adapts to body dimensions of recipient: no influence of donor gender on renal function after transplantation.

    PubMed

    Tent, H; Lely, A T; Toering, T J; San Giorgi, M R M; Rook, M; Lems, S P M; Hepkema, B G; Hofker, H S; Ploeg, R J; Homan van der Heide, J J; Navis, G J

    2011-10-01

    Female kidneys and kidneys from small donors have been suggested to perform worse after kidney transplantation. Here, we evaluate the impact of gender and body dimensions on posttransplantation GFR in living donor transplantation. Two hundred and ninety-three donor-recipient pairs, who were transplanted at our center were evaluated. All pairs had detailed renal function measurement ((125) I-iothalamate and (131) I-hippuran) 4 months predonation in the donor and 2.5 months posttransplantation in donor and recipient. For 88 pairs, 5 years of recipient follow-up was available. Delta GFR was calculated as (recipient GFR-donor single kidney GFR). Recipients of both male and female kidneys had similar renal function at early and long term after transplantation. Male recipients had higher ERPF, ΔGFR and ΔERPF at both time points. Kidneys of donors smaller than their recipient had higher ΔGFR and ΔERPF than kidneys of larger donors at both time points (p < 0.05). In multivariate analysis, ΔGFR was predicted by donor/recipient BSA-ratio together with transplantation related factors (R(2) 0.19), irrespective of donor and recipient gender. In conclusion, in living donor transplantation, female kidneys perform as well as male donor kidneys. Kidneys adapt to the recipient's body size and demands, independent of gender, without detrimental effects in renal function and outcome up to mid-long term.

  10. Basal renal function reserve and mean kidney dose predict future radiation-induced kidney injury in stomach cancer patients.

    PubMed

    Yavas, Guler; Elsurer, Rengin; Yavas, Cagdas; Ata, Ozlem

    2014-02-01

    Adjuvant chemoradiotherapy (CRT) improves the survival in patients with locally advanced stomach cancer. The kidneys are the major dose-limiting organs for radiotherapy (RT) in upper abdominal cancers. We aimed to evaluate the impact of adjuvant CRT on renal function of patients with stomach cancer. Fifty-nine stomach cancer patients who underwent postoperative CRT were included. Demographic parameters (age, gender), and basal and 12th-month biochemical parameters were recorded. Mean kidney dose (MKD) administered was determined. Estimated glomerular filtration rate (eGFR) was calculated by modification of diet in renal disease formula. Fifty-nine patients were recruited (age 60.8 ± 11.9 years; female/male 25/34; follow-up duration 15.6 ± 9.8 months). Twenty-one patients (35.6 %) had basal eGFR <90 ml/min/1.73 m(2). When the basal and 12th-month eGFR was compared, eGFR decreased in 27 patients (45.8 %), whereas eGFR remained stable in 32 (54.2 %) patients. Cox regression analyses revealed that a MKD ≥1,500 cGy and basal eGFR <90 ml/min/1.73 m(2) significantly increased the risk of a decreased eGFR at 12th month (HR = 2.288, 95 % CI 1.009-5.188, p = 0.048 and HR = 2.854, 95 % CI 1.121-7.262, p = 0.028, respectively). MKD ≥1,500 cGy and a basal eGFR <90 ml/min/1.73 m(2) significantly increased the risk of a decreased eGFR at 12th month. We suggest that patients with stomach cancer be evaluated for their basal renal reserve prior to RT, and it may be more convenient to further minimize the dose to the kidneys with more sophisticated RT techniques in patients with stomach cancer, more specifically in patients with decreased renal reserve.

  11. Association of age and BMI with kidney function and mortality: a cohort study.

    PubMed

    Lu, Jun Ling; Molnar, Miklos Z; Naseer, Adnan; Mikkelsen, Margit K; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

    2015-09-01

    Compared with normal weight, obesity might be associated with worse clinical outcomes, including chronic kidney disease. Whether this association is modified by age is not known. We investigated the association of BMI with progressive loss of kidney function and all-cause mortality in US veterans. In a national cohort of 3,376,187 US veterans with an estimated glomerular filtration rate (eGFR) of more than 60 mL/min per 1·73 m(2), we assessed the association of BMI in patients of different ages (<40 years, 40 years to <50 years, 50 years to <60 years, 60 years to <70 years, 70 years to <80 years, and ≥80 years) with loss of kidney function and with all-cause mortality in logistic regression models and Cox proportional hazards models adjusted for ethnic origin, sex, comorbidities, medications, and baseline eGFR. 274,764 (8·1%) of 3,376,187 veterans had a rapid decline in kidney function (decrease in slope of >5 mL/min per 1·73 m(2)). The lowest risk for loss of kidney function was noted in patients with BMI of at least 25 kg/m(2) but less than 30 kg/m(2). A generally consistent U-shaped association was noted between BMI and rapid loss of kidney function that was more prominent with increasing age, except in the patients younger than 40 years, in whom BMI did not seem to be predictive of renal function impairment. 672,341 veterans died (28·7 per 1000 patient-years, 95% CI 28·6-28·7) over a median follow-up of 6·8 years (IQR 6·5-7·7). BMI also showed a U-shaped association with mortality, which was similar in all age groups. A BMI of 30 kg/m(2) or more is associated with rapid loss of kidney function in patients with eGFR of at least 60 mL/min per 1·73 m(2), and this association is accentuated in older patients. A BMI of 35 kg/m(2) or more is also associated with high mortality. A BMI of at least 25 kg/m(2) but less than 30 kg/m(2) is associated with the best clinical outcomes. National Institute of Health, Memphis VA Medical Center, Long Beach VA

  12. Antigravity suit inflation - Kidney function and cardiovascular and hormonal responses in men

    NASA Technical Reports Server (NTRS)

    Geelen, Ghislaine; Kravik, Stein E.; Hadj-Aissa, Aoumeur; Leftheriotis, Georges; Vincent, Madeleine

    1989-01-01

    The effect of the lower body positive pressure (LBPP) on kidney function in normal men was investigated in experiments in which the subjects underwent 30 min of sitting and then were subjected to 4.5 h of 70-deg head-up tilt. During the last 3 h of the tilt period, an antigravity suit (60 T legs, 30 T abdomen) was applied. The results showed that LBPP induces a significant increase in effective renal plasma flow and significant changes in the kidney excretory patterns, which were similar to those observed during a water immersion or the early phase of bed rest.

  13. Antigravity suit inflation - Kidney function and cardiovascular and hormonal responses in men

    NASA Technical Reports Server (NTRS)

    Geelen, Ghislaine; Kravik, Stein E.; Hadj-Aissa, Aoumeur; Leftheriotis, Georges; Vincent, Madeleine

    1989-01-01

    The effect of the lower body positive pressure (LBPP) on kidney function in normal men was investigated in experiments in which the subjects underwent 30 min of sitting and then were subjected to 4.5 h of 70-deg head-up tilt. During the last 3 h of the tilt period, an antigravity suit (60 T legs, 30 T abdomen) was applied. The results showed that LBPP induces a significant increase in effective renal plasma flow and significant changes in the kidney excretory patterns, which were similar to those observed during a water immersion or the early phase of bed rest.

  14. Impact of chronic kidney disease on quality of life, lung function, and functional capacity.

    PubMed

    Teixeira, Carolina Guimarães; Duarte, Maria do Carmo M B; Prado, Cecília Maciel; Albuquerque, Emídio Cavalcanti de; Andrade, Lívia B

    2014-01-01

    To evaluate the impact of the chronic kidney disease (CKD) on quality of life, from the children's and their parents' perspective, respiratory muscle strength, lung function, and functional capacity in children and adolescents. Cross-sectional study of children with CKD aged 8 to 17 years. Those incapable of taking the tests were excluded. After an interview, quality of life by Pediatric Quality of Life Inventory) (PedsQL(TM)), muscular strength, pulmonary function tests, and the 6-minute walking test (6MWT) were applied. Student's t-test, ANOVA (difference in means), and Pearson's coefficient of correlation were used. The level of significance was set at 5%. Of the 40 patients, the mean distance walked at the 6MWT was 396 meters, and the mean final score at the quality of life test as perceived by the children and parents was 50.9 and 51, respectively. From the children's perspective, the transplanted patients had a higher quality of life score when compared to those undergoing hemodialysis (p<0.001); those who practiced physical activity had better quality of life when compared to the sedentary children (p<0.001). From the children's and the parents' perspectives, the male gender had a higher quality of life score (p<0.05). There was a positive correlation between the distance walked at the 6MWT and age, height, final PedsQL(TM), forced vital capacity (FVC), and forced expiratory volume in the first second (FEV1), as well as a negative correlation between FEV1/FVC and the distance walked. A significant reduction in the quality of life and the functional capacity was observed in children with CKD, influenced by the type of treatment, gender, and sedentary life style. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  15. Radionuclide determination of individual kidney function in the treatment of chronic renal obstruction

    SciTech Connect

    Belis, J.A.; Belis, T.E.; Lai, J.C.; Goodwin, C.A.; Gabriele, O.F.

    1982-04-01

    Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The /sup 99m/Tc diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The /sup 131/I orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential /sup 99m/Tc diethylenetriaminepentaacetic acid and /sup 131/I orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients. The preservation of cortical perfusion on /supb 99m/Tc diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the /sup 131/I orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively.

  16. Radionuclide determination of individual kidney function in the treatment of chronic renal obstruction.

    PubMed

    Belis, J A; Belis, T E; Lai, J C; Goodwin, C A; Gabriele, O F

    1982-04-01

    Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The 99mtechnetium diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The 131iodine orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential 99mtechnetium diethylenetriaminepentaacetic acid and 131iodine orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients. The preservation of cortical perfusion on 99mtechnetium diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the 131iodine orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively.

  17. Mineral and Bone Disorder and Its Association with Cardiovascular Parameters in Chinese Patients with Chronic Kidney Disease.

    PubMed

    Zhou, Chu; Wang, Fang; Wang, Jin-Wei; Zhang, Lu-Xia; Zhao, Ming-Hui

    2016-10-05

    Mineral and bone disorder (MBD), especially hyperphosphatemia, is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD). However, CKD-MBD among Chinese population was poorly studied. This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD. Chinese Cohort Study of Chronic Kidney Diseas