American journal of nephrology
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Vitamin D receptor modulators (VDRMs) are indicated for secondary hyperparathyroidism in chronic kidney disease (CKD). Clinical observations demonstrate that VDRM therapy provides cardiovascular (CV) benefit in CKD. Current on-market VDRMs have a narrow therapeutic index at 1- to 4-fold [hypercalcemic toxicity vs. parathyroid hormone (PTH)-suppressing efficacy]. Hypercalcemia leads to the need for frequent drug dose titration and serum calcium (Ca) monitoring. A VDRM with a wider therapeutic index and beneficial CV effects will be clinically useful. ⋯ Structurally similar VDRMs can exhibit distinctly different hypercalcemic effects in 5/6 NX uremic rats. While differences exist for the Ca and CV effects of VS-110 and VS-411, the clinical implications are unclear. VS-110's results are promising but clinical outcome studies need to be performed.
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Acute kidney injury (AKI) is a common complication in advanced liver dysfunction. Our aim is to clarify the mechanisms of acute hepatic failure (AHF)-associated AKI. ⋯ AHF-associated AKI seems to be mediated by renal tubular epithelial cell injury with bile pigment accumulation, impaired microcirculation caused by PTC endothelial cell injury with depletion of endothelial nitric oxide synthase and angiogenic factors, and by a decrease in RBC velocity and renal inflammation. Multiple mechanisms including tubular and PTC injuries and renal inflammation may be involved in the development of AHF-associated AKI.
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Randomized Controlled Trial Multicenter Study
Dialysis dose and intradialytic hypotension: results from the HEMO study.
Intradialytic hypotension (IDH) is common and is associated with increased morbidity and mortality in chronic hemodialysis patients. A higher dialysis 'dose' may generate transient intradialytic osmotic gradients, predisposing to intracellular fluid shifts and resulting in hypotension. ⋯ Higher dialysis dose, at relatively constrained treatment times, may associate with an increased risk of IDH. These findings support the possibility that rapidity of intradialytic reductions in plasma osmolality may play an important role in mediating hemodynamic instability during dialysis.
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Multicenter Study Observational Study
Heart rate variability is a predictor of mortality in chronic kidney disease: a report from the CRIC Study.
Low heart rate variability (HRV) is a risk factor for adverse outcomes in the general population. We aimed to determine the factors associated with HRV and evaluate the association between low HRV and clinical outcomes in patients with chronic kidney disease (CKD). ⋯ In a large cohort of patients with CKD, multiple risk factors for renal and cardiovascular diseases were associated with lower HRV. Lower HRV was not associated with increased risk for renal or cardiovascular outcomes, but both low and high RMSSD were associated with increased risk for all-cause mortality. In conclusion, HRV measured by RMSSD may be a novel and independent risk factor for mortality in CKD patients.
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The C-terminal agrin fragment (CAF) is a cleavage product of agrin, the major proteoglycan of the glomerular basement membrane. This article studies if CAF could serve as a biomarker for renal function in renal transplant recipients. ⋯ CAF is a promising new and fast biomarker for kidney function and may serve as a new tool for the early detection of DGF.