Kidney international
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Kidney international · Jul 2012
Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients.
Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D-binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) from a cohort of incident hemodialysis patients. Vitamin D-binding protein was measured from stored serum samples. ⋯ Bioavailable, but not total, 25(OH)D and 1,25(OH)(2)D were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH)D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis.
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Kidney international · Jul 2012
Targeted proximal tubule injury triggers interstitial fibrosis and glomerulosclerosis.
Chronic kidney disease (CKD) remains one of the leading causes of death in the developed world, and acute kidney injury (AKI) is now recognized as a major risk factor in its development. Understanding the factors leading to CKD after acute injury are limited by current animal models of AKI, which concurrently target various kidney cell types including epithelial, endothelial, and inflammatory cells. Here, we developed a mouse model of kidney injury using the Six2-Cre-LoxP technology to selectively activate expression of the simian diphtheria toxin (DT) receptor in renal epithelia derived from the metanephric mesenchyme. ⋯ Acute injury was promptly followed by inflammatory cell infiltration and robust tubular cell proliferation, leading to complete recovery after a single toxin insult. In striking contrast, three insults to renal epithelial cells at 1-week intervals resulted in maladaptive repair with interstitial capillary loss, fibrosis, and glomerulosclerosis, which was highly correlated with the degree of interstitial fibrosis. Thus, selective epithelial injury can drive the formation of interstitial fibrosis, capillary rarefaction, and potentially glomerulosclerosis, substantiating a direct role for damaged tubule epithelium in the pathogenesis of CKD.
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Kidney international · Jul 2012
ReviewCritical care nephrology: management of acid-base disorders with CRRT.
Normal acid-base homeostasis is severely challenged in the intensive care setting. In this review, we address acid-base disturbances, with a special focus on the use of continuous (rather than intermittent) extracorporeal technologies in critical ill patients with acute kidney injury. We consider hypercapnic acidosis and lactic acidosis as examples in which continuous modalities may have different roles and indications than the traditional intermittent approaches to renal replacement therapy. ⋯ Most often, lactic acidosis is a biomarker denoting unfavorable outcomes, rather than an intrinsic pathogenetic mechanism. Extracorporeal procedures may assist in the removal of pathogenic drugs or toxins, as well as partially correcting acidemia. Whether or not these approaches will permit normalization of systemic pH, and the impact of these approaches on patient outcomes, needs to be addressed with prospective controlled trials.
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Kidney international · Jul 2012
Randomized Controlled TrialThe health-related quality of life was not improved by targeting higher hemoglobin in the Normal Hematocrit Trial.
The Normal Hematocrit Trial (NHT) was the largest trial of epoetin randomizing 1265 hemodialysis patients with cardiac disease to lower (9-11 g/dl) or higher (13-15 g/dl) hemoglobin (Hgb), hypothesizing that higher Hgb would reduce mortality, and improve survival and quality of life. The trial was terminated early, and a 1998 publication reported that targeting higher hematocrit levels led to an insignificant increase in the primary end points (death or myocardial infarct), or risk ratio 1.3, 95% confidence interval (CI), 0.9-1.90, but the P-value was not given, and all-cause death risk was not reported. A higher target reportedly did not increase hospitalization rates, but did significantly improve the 'physical function' domain of quality of life. ⋯ Among these, the 1998 article reported interim trial results with only the adjusted CI but did not state that the unadjusted CIs were 99.912th percentile, and despite being a secondary end point, reported only the association of achieved Hgb with higher quality of life score. Randomization to the higher target had actually increased the risk for the primary end point (risk ratio 1.28, 95% CI=1.06-1.56; P=0.0112; 99.92% CI=0.92-1.78), the risk of death (risk ratio 1.27, 95% CI=1.04-1.54), non-access thrombotic events (P=0.041), and hospitalization rate (P=0.04), while 'physical function' did not improve (P=0.88). Hence, disclosure of these results in the 1998 publication or access to the FDA-filed report on the NHT in the late 1990s would likely have led to earlier concerns about epoetin safety and greater doubts about its benefits.
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Kidney international · Jul 2012
CommentA physician's perseverance uncovers problems in a key nephrology study.
The Normal Hematocrit Cardiac Trial, published in 1998, was a foundational study testing erythropoietin analog treatment to normal hematocrit targets. It served as a warning that erythropoietin replacement was not a panacea. ⋯ Coyne shows that the published results did not completely and clearly represent the study's actual results. We discuss the implications and make recommendations to prevent such occurrences.