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Concept: Nephrology


BACKGROUND: Maintenance hemodialysis (HD) patients universally suffer from excess toxin load. Hemodiafiltration (HDF) has shown its potential in better removal of small as well as large sized toxins, but its efficacy is restricted by inter-compartmental clearance. Intra-dialytic exercise on the other hand is also found to be effective for removal of toxins; the augmented removal is apparently obtained by better perfusion of skeletal muscles and decreased inter-compartmental resistance. The aim of this trial is to compare the toxin removal outcome associated with intra-dialytic exercise in HD and with post-dilution HDF.Methods/designThe main hypothesis of this study is that intra-dialytic exercise enhances toxin removal by decreasing the inter-compartmental resistance, a major impediment for toxin removal. To compare the HDF and HD with exercise, the toxin rebound for urea, creatinine, phosphate, and beta2-microglobulin will be calculated after 2 hours of dialysis. Spent dialysate will also be collected to calculate the removed toxin mass. To quantify the decrease in inter-compartmental resistance, the recently developed regional blood flow model will be employed. The study will be single center, randomized, self-control, open-label prospective clinical research where 15 study subjects will undergo three dialysis protocols (a) high flux HD, (b) post-dilution HDF, © high flux HD with exercise. Multiple blood samples during each study session will be collected to estimate the unknown model parameters. DISCUSSION: This will be the first study to investigate the exercise induced physiological change(s) responsible for enhanced toxin removal, and compare the toxin removal outcome both for small and middle sized toxins in HD with exercise and HDF. Successful completion of this clinical research will give important insights into exercise effect on factors responsible for enhanced toxin removal. The knowledge will give confidence for implementing, sustaining, and optimizing the exercise in routine dialysis care. We anticipate that toxin removal outcomes from intra-dialytic exercise session will be comparable to that obtained by standalone HDF. These results will encourage clinicians to combine HDF with intra-dialytic exercise for significantly enhanced toxin removal.Trial number, NCT01674153.

Concepts: Chronic kidney disease, Nephrology, Dialysis, Clinical trial, Effectiveness, Hemodialysis, Renal replacement therapy, Clinical research


Prolonged hypothermic storage causes ischemia-reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK-2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia-hypoxia challenge stabilized the HK-2 cellular structure, diminished cytoplasmic translocation of high-mobility group box (HMGB) 1 and suppressed NF-κB activation. In the syngeneic Lewis-to-Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase-3 expression, localized HMGB-1 within nuclei and prevented TLR-4/NF-κB activation in tubular cells; serum pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis-to-Lewis isografts and Fischer-to-Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF-1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long-term graft survival.

Concepts: Protein, Kidney, Nephrology, Cell nucleus, Cell, Cytoplasm, Organ transplant, Protection


Kawasaki disease (KD) is a systemic vasculitis and affects many organ systems. It often presents sterile pyuria, microscopic hematuria, and proteinuria due to renal involvement. The aims of this study were to define clinical characteristics of acute KD patients with pyuria and to analyze meaning of pyuria in KD.

Concepts: Nephrology, Vasculitis, Nephrotic syndrome, Arthralgia, Glomerulonephritis, Kawasaki disease, Urinalysis, IgA nephropathy


The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m(2)) and longstanding type 2 diabetes not adequately controlled with insulin therapy, which is a difficult-to-treat population, with limited therapeutic options and a high susceptibility to hypoglycemia.

Concepts: Renal failure, Nephrology, Dialysis, Insulin, Diabetes mellitus type 2, Diabetes mellitus, Diabetes mellitus type 1, Renal function


BACKGROUND: Fibroblast growth factor 23 (FGF23) is an important hormone in the regulation of phosphate metabolism. It is unclear whether FGF23 is associated with carotid artery calcification (CAAC) in predialysis patients. The present study aimed to clarify the relationship between FGF23 and CAAC in patients with chronic kidney disease (CKD) who were not on dialysis. METHODS: One-hundred ninety-five predialysis CKD patients were enrolled in this cross-sectional study. CAAC was assessed using multidetector computed tomography, and the prevalence of CAAC was examined. Intact FGF23 was measured in each patient. The risk factors for CAAC were evaluated using a logistic regression model. RESULTS: We found CAAC in 66% of the patients. The prevalence of CAAC significantly increased across CKD stages: it was 37% in CKD stages 1–2, 58% in stage 3; 75% in stage 4, and 77% in stage 5 (p < 0.01). In multivariate analysis, smoking, diabetes mellitus and log FGF23 were each identified as risk factors for CAAC. The study population was divided in quartiles of FGF23 levels. Compared with the lowest FGF23 quartile, each subsequent quartile had a progressively higher odds ratio (OR) for CAAC, adjusted for confounders (ORs [95% confidence interval] of 2.34 [0.78 to 7.31], 5.28 [1.56 to 19.5], and 13.6 [2.92 to 74.6] for the second, third, and fourth quartiles, respectively. CONCLUSIONS: The prevalence of CAAC is increased with the decline in the kidney function. FGF23 is independently related to CAAC in patients with CKD who are not on dialysis.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Erythropoietin, Epidemiology, Diabetes mellitus, Medical statistics


Chronic renal failure (CRF) is associated with the development of secondary hyperparathyroidism and vascular calcifications. We evaluated the efficacy of PA21, a new iron-based non-calcium phosphate binder, in controlling phosphocalcic disorders and preventing vascular calcifications in uremic rats. Rats with adenine-diet-induced CRF were randomized to receive either PA21 0.5%, 1.5% or 5% or calcium carbonate (CaCO3) 3% in the diet, for 4 weeks and were compared with uremic and non-uremic control groups. After 4 weeks' phosphate binder treatment, serum calcium, creatinine and body weight were similar between all CRF groups. Serum phosphorus was reduced with CaCO3 3% (2.06 mmol/l, P≤0.001), PA21 1.5% (2.29 mmol/l, P<0.05) and PA21 5% (2.21 mmol/l, P≤0.001) versus CRF controls (2.91 mmol/l). Intact parathyroid hormone was strongly reduced in the PA21 5% and CaCO3 3% CRF groups to a similar extent (1138 and 1299 pg/ml, respectively) versus CRF controls (3261 pg/ml, both P≤0.001). A lower serum fibroblast growth factor 23 concentration was observed in the PA21 5%, compared with CaCO3 3% and CRF, control groups. PA21 5% CRF rats had a lower vascular calcification score compared with CaCO3 3% CRF rats and CRF controls. In conclusion, PA21 was as effective as CaCO3 at controlling phosphocalcic disorders but superior in preventing the development of vascular calcifications in uremic rats. Thus, PA21 represents a possible alternative to calcium-based phosphate binders in CRF patients.

Concepts: Renal failure, Nephrology, Carbon dioxide, Parathyroid hormone, Calcium carbonate, Hyperparathyroidism, Organ failure, Phosphate binders


Kidney stones (nephrolithiasis) are a widespread disease. Thus, blocking stone formation and finding new therapeutic methods is an important area of study. Diosmin (a major component of the bile) is known to have antioxidant as well as renoprotective effects. The present investigation aimed to evaluate the effect of diosmin on renal tissue protection in rats with ethylene glycol-induced nephrolithiasis.

Concepts: Kidney, Nephrology, Vitamin D, Urinary bladder, Vitamin C, Uric acid, Kidney stone, Oxalate


Home-based renal replacement therapy (RRT) [peritoneal dialysis (PD) and home hemodialysis (HHD)] offers independent quality of life and clinical advantages compared to conventional in-center hemodialysis. However, follow-up may be less complete for home dialysis patients following a change in care settings such as post hospitalization. We aim to implement a Home Dialysis Virtual Ward (HDVW) strategy, which is targeted to minimize gaps of care.

Concepts: Chronic kidney disease, Nephrology, Dialysis, Hemodialysis, Peritoneum, Renal dialysis


Bixalomer (BXL) was developed to improve gastrointestinal symptoms and reduce constipation, relative to sevelamer hydrochloride, in hemodialysis patients. We prospectively evaluated the safety and effectiveness of switching maintenance dialysis patients from sevelamer hydrochloride to BXL.

Concepts: Nephrology, Dialysis, Effectiveness, Cellular respiration, Hemodialysis, Metabolic acidosis, Renal dialysis, Sevelamer


Renal fibrosis represents a common pathway leading to progression of chronic kidney disease. Renal interstitial fibrosis is characterized by extensive fibroblast activation and excessive production and deposition of extracellular matrix (ECM), which leads to progressive loss of kidney function. There is no effective therapy available clinically to halt or even reverse renal fibrosis. Although activated fibroblasts/myofibroblasts are responsible for the excessive production and deposition of ECM, their origin remains controversial. Recent evidence suggests that bone marrow-derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. Understanding the molecular signaling mechanisms underlying the recruitment and activation of the bone marrow-derived fibroblast precursors will lead to novel therapy for the treatment of chronic kidney disease. In this review, we summarize recent advances in our understanding of the recruitment and activation of bone marrow-derived fibroblast precursors in the kidney and the development of renal fibrosis and highlights new insights that may lead to novel therapies to prevent or reverse the development of renal fibrosis.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Erythropoietin, Collagen, Extracellular matrix, Renal physiology