Contributions to nephrology
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Acute kidney injury (AKI) commonly occurs in hospitalized patients and is independently and strongly associates with morbidity and mortality. The clinical benefits of a timely and definitive diagnosis of AKI have not been fully realized due to limitations imposed by the use of serum creatinine and urine output to fulfill diagnostic criteria. These restrictions often lead to diagnostic delays, potential misclassification of actual injury status, and provide little information regarding underlying cause. ⋯ Promising diagnostic injury markers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18) and liver-type fatty acid binding protein (L-FABP). However, there are currently insufficient data on damage biomarkers to support their use for AKI staging. Rigorous validation studies measuring the association between the novel damage biomarker(s) and clinically relevant outcomes are needed.
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Several new biomarkers of kidney damage have been characterized and are being validated in clinical studies. These damage biomarkers complement existing conventional biomarkers of kidney function (e.g. serum creatinine, serum urea, and urine output) that are currently utilized to diagnose and stage acute kidney injury (AKI). Both functional and damage biomarkers provide an opportunity to identify patients with AKI who are at risk for a less favorable prognosis in terms of worsening damage or further declines in kidney function and likelihood of need for renal replacement. ⋯ Set cut-offs for various biomarkers and their bedside utility are forthcoming and will be in part determined by regulatory intended use guidelines, platform standardization, and inter-laboratory calibration. There remain many unresolved areas of AKI biomarker use in selected syndromes of AKI (e.g. cardiorenal syndrome, hepatorenal syndrome). As clinicians gain experience with AKI biomarkers, clinical care plans that incorporate them into routine care will shortly follow.
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Chronic kidney disease and atrial fibrillation (AF) commonly coexist, and data suggest that renal patients have AF rates in excess of double that encountered in the general population. These patients are at increased risk of stroke, regardless of the presence or absence of AF. Furthermore, a lower GFR causes increased thromboembolic risk in patients with AF - independent of other risk factors. ⋯ The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion. There is a need for large randomised control trials in patients with renal insufficiency and on haemodialysis to provide a bank of high-quality scientific data on which clinicians can base their management decisions. Until then, we must adopt a pragmatic approach which involves careful consideration of the relative risk of stroke and bleeding in each individual patient.
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The type II sodium-dependent Pi (NaPi) cotransporters (NaPi-IIa, NaPi-IIb and NaPi-IIc) contribute to renal and intestinal Pi absorption. 1,25-Dihydroxyvitamin D [1,25(OH)2D3] is an important factor for NaPi-II transporters in the small intestine and kidney. In a previous study, low levels of 1,25(OH)2D3 appeared to suppress the expression of renal NaPi cotransporters. We identified a functional vitamin D receptor-responsive element in the human NaPi-IIa and NaPi-IIc genes in renal epithelial cells. ⋯ Klotho functions as a co-receptor for FGF23 and is increased by 1,25(OH)2D3. Klotho induces phosphaturia by inhibiting the renal NaPi-IIa transporter. In this review, we discuss the roles of 1,25(OH)2D3/VDR in the regulation of renal type II NaPi cotransporters in the kidney and small intestine.