Nephron Clinical Practice最新文献

Background: There is controversy concerning the compared rates of decline of residual kidney function (RKF) in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD).

Objectives and method: Following an observational, multicenter design, we studied 493 patients initiating peritoneal dialysis (PD) in four different Spanish units. We explored the effect of the PD modality on the rate of decline of RKF and the probability of anuria during follow-up. We applied logistic regression for intention-to-treat analyses, and linear mixed models to explore time-dependent variables, excluding those affected by indication bias.

Main results: Patients started on APD were younger and less comorbid than those initiated on CAPD. Baseline RKF was similar in both groups (p = 0.50). Eighty-seven patients changed their PD modality during follow-up. The following variables predicted a faster decline of RKF: higher (rate of decline) or lower (anuria) baseline RKF, younger age, proteinuria, nonprimary PD, use of PD solutions rich in glucose degradation products, higher blood pressure, and suffering peritonitis or cardiovascular events during follow-up. Overall, APD was not associated with a fast decline of RKF, but stratified analysis disclosed that patients with lower baseline RKF had an increased risk for this outcome when treated with this technique (HR: 2.26, 95% CI: 1.09-4.82, p = 0.023). Moreover, the probability of anuria during follow-up was overtly higher in APD patients (HR: 3.22, 95% CI: 1.25-6.69, p = 0.002).

Conclusions: Starting PD patients directly on APD is associated with a faster decline of RKF and a higher risk of developing anuria than doing so on CAPD. This detrimental effect is more marked in patients initiating PD with lower levels of RKF.

Background/aims: Fatty acid-binding proteins (FABPs) are a family of intracellular lipid chaperones. Among FABPs, FABP1 (liver FABP) is expressed in proximal tubular epithelial cells in the kidney, and urinary FABP1 has been reported to reflect damage of proximal tubular epithelial cells. However, roles of other FABP isoforms in renal pathologies have not been reported. Recently, FABP4 (adipocyte FABP/aP2) was reported to be expressed in peritubular capillaries (PTCs), but not in glomerular capillaries in the normal kidney. We examined the hypothesis that pathological conditions alter the level and localization of FABP4 expression in the kidney, which mediates renal dysfunction.

Methods: A total of 112 consecutive patients who underwent renal biopsy were retrospectively enrolled. Expression of FABP4 protein and mRNA in the kidney was examined by immunohistochemistry and in situ hybridization, respectively. The ratio of FABP4-positive area to total area within glomeruli (G-FABP4-Area), urinary protein level (U-Protein), and change in estimated glomerular filtration rate (eGFR) 1 year after biopsy were examined.

Results: FABP4 protein and mRNA were expressed not only in PTCs, but also in endothelial cells and macrophages in the glomerulus. G-FABP4-Area was correlated with U-Protein (r = 0.497, p < 0.001). As a subanalysis, in patients with IgA nephropathy (n = 34), G-FABP4-Area was significantly larger in cases with an endocapillary proliferative lesion, and change in eGFR was negatively correlated with G-FABP4-Area at baseline (r = -0.537, p = 0.008).

Conclusion: Ectopic FABP4 expression in the glomerulus is induced by renal diseases and is closely associated with proteinuria and renal dysfunction.

Since the early 2000s, considerable advances have been achieved in the understanding of molecular pathomechanisms of human membranous nephropathy (MN), inspired by studies of Heymann nephritis, a faithful experimental model. These studies led to the identification of neutral endopeptidase, the type-M phospholipase A2 receptor (PLA2R), and cationic bovine serum albumin as target antigens of circulating and deposited antibodies in neonatal alloimmune, adult 'idiopathic', and early childhood MN, respectively. A genome-wide association study further showed a highly significant association of the PLA2R1 and the HLA-DQA1 loci with idiopathic MN in patients of white ancestry. The time has come to revisit the spectrum of MN based on the newly identified antigen-antibody systems which should be considered as molecular signatures of the disease, challenging the uniform histological definition. Although some uncertainties remain as to the pathogenic effects of anti-PLA2R antibodies because of the lack of an appropriate experimental model, the value of these antibodies as biomarkers for diagnosis and disease activity is increasingly being recognized. It is not exaggerated to state that they have induced a paradigm shift in the monitoring of patients with MN, thus opening a new era of personalized medicine.

Background: Severe hyper- and hyponatraemia is associated with significant risks, yet its correction can also have serious consequences when implemented too fast or inadequately. The safe correction of serum sodium levels is particularly challenging when renal replacement therapy (RRT) is required.

Methods: Using 2 case scenarios, we aim to illustrate a simple method of correcting hyper- and hyponatraemia safely by step-wise manipulation of the dialysate/replacement fluid.

Results: During continuous RRT, hypernatraemia can be corrected effectively and safely by adding small pre-calculated amounts of 30% NaCl to the dialysate/replacement fluid bags aiming for a [Na(+)] in the fluid that allows safe equilibration and correction of the serum [Na(+)]. To correct hyponatraemia safely, pre-calculated amounts of sterile water can be added in a step-wise manner to achieve a fluid [Na(+)] that equals the desired target serum [Na(+)].

Conclusion: During continuous RRT, the step-wise adjustment of [Na(+)] of dialysate/replacement fluids offers a safe and reliable method to correct sodium disorders.

Background/aims: High sodium intake is associated with adverse cardiovascular and renal outcomes in people with chronic kidney disease (CKD), and simple methods to facilitate assessment of sodium intake are required. The objective of this study was to develop a new formula to estimate 24-hour urinary sodium (24hUNa) excretion from urinary Na concentration measured on an early morning urine specimen (EM UNa).

Methods: Seventy participants from a prospective cohort of patients with CKD stage 3 in primary care, the Renal Risk in Derby (RRID) study, agreed to collect an additional EM UNa on the day after completing a 24-hour urine collection. A formula to estimate 24hUNa from EM UNa and body weight was developed using the coefficients from a multivariable linear regression equation. The accuracy of the formula was tested by calculating the P30 (proportion of estimates within 30% of measured sodium exection), and the ability of the estimated 24hUNa to discriminate between measured sodium intake above or below 100 mmol/day was assessed by receiver operating characteristic (ROC) curve. A Bland-Altman plot was used to estimate the bias and limits of agreement between estimated and measured 24hUNa. Seventy-four additional paired 24hUNa and EM UNa from 50 CKD stage 3 patients in the RRID study were used to validate the formula.

Results: The mean difference between measured and estimated 24hUNa was 2.08 mmol/day. Measured and estimated 24hUNa were significantly correlated (r = 0.55; p < 0.001) but accuracy of estimated 24hUNa was low (P30 = 60%). Analysis of the ROC curve with a cut-off point >100 mmol/day yielded an area under the curve of 0.668, sensitivity of 0.85 and specificity of 0.52.

Conclusions: We have developed a simple formula to identify people with a high sodium intake from EM UNa, suitable for use in large-cohort or population studies.

In recent years, there has been considerable interest in cellular and tissue responses to injury that result in the deposition of extracellular matrix, collagen, elastic fibers, and the histopathological development of fibrosis. In the myocardium, fibrosis results in many recognizable clinical features, including PR interval prolongation, heart block, bundle branch block, left ventricular dyssynergy, anisotropy, atrial fibrillation, ventricular arrhythmias, systolic and diastolic dysfunction, heart failure, and cardiac death. In the kidneys, fibrosis in the glomerulus leads to glomerular sclerosis, and in the inner cortex and medulla, tubulointerstitial fibrosis leads to a reduction in renal filtration function and rapidly progressive chronic kidney disease. There are a great number of potential early mediators of cellular damage in response to events such as ischemia, neurohormonal activation, biomechanical stretch, and abnormal cell signaling. However, many studies suggest that interstitial cells in both organs, including macrophages, T lymphocytes, fibroblasts, and myofibroblasts, have common communication systems that utilize galectin-3 and transforming growth factor-β that result in the upregulation and proliferation of fibroblasts and myofibroblasts, which produce and secrete procollagen I. Procollagen I cross-links in the extracellular space to form mature collagen, which is a fundamental unit of organ fibrosis. Future research will be concentrating on the pathogenic mechanisms that turn on fibrosis and on therapeutic targets that can either prevent the activation of fibroblasts or limit their repair response to injury.

Pattern recognition receptors (PRRs) are now recognized to be key triggers of injury in a variety of renal diseases. Several families of these receptors are present in the kidney, and recent data suggest that they are differentially expressed and regulated in the kidney. This study evaluated the interaction between two distinct PRRs that are expressed in the kidney, i.e. TLR2 (Toll-like receptor 2) and the NLRP3 inflammasome. The regulation and activation of these receptors in primary renal tubular epithelial (RTE) cells from murine kidneys were evaluated. RTE cells were extracted from WT and NLRP3-mutant mice and treated ex vivo with ligands specific for TLR2 or NLRP3. We found that TLR2 upregulated NLRP3 as well as its substrate IL-1β, and that signaling through the NLRP3 inflammasome induced RTE cell necrosis. The results of this study suggest a previously unknown interaction between TLR2 and NLRP3 in primary RTE cells and highlight the importance of the cross talk that occurs in kidney-related PRRs. Understanding how PRRs are regulated is important for the design of rationale therapeutic strategies to modulate these receptors in renal disease.

Background: Desmopressin (DDAVP) is often used prior to procedures to minimize bleeding in patients with renal failure; however, there is little evidence to support this practice. The objectives of this study were to evaluate the practice of administration of DDAVP prior to procedures within our division and to determine the number of bleeding episodes for patients who received DDAVP compared to those who did not.

Methods: Hospital records of patients who underwent renal biopsy or central line placement between April 2006 and March 2008 were reviewed. Patients with glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) were identified and subcategorized into three groups: group A GFR <15 ml/min/1.73 m(2), group B GFR 15-29 ml/min/1.73 m(2), and group C GFR 30-60 ml/min/1.73 m(2). The number of bleeding events was noted in each group.

Results: No significant difference was found in the number of bleeding events between those who received and did not receive DDAVP overall and in each GFR group. A possible trend towards the benefit with treatment in group A was observed.

Conclusion: There was no significant reduction in bleeding for those who received DDAVP which questions the validity of this practice. Patients with GFR <15 ml/min/1.73 m(2) may possibly derive benefit.

Background: Efficacy of intravenous (IV) volume expansion in preventing contrast-induced acute kidney injury (CI-AKI) is well known. However, the role of oral hydration has not been well established. The aim of this work was to evaluate the efficacy of oral hydration in preventing CI-AKI.

Methods: We prospectively randomized 225 patients undergoing coronary angiography and/or percutaneous coronary intervention in either oral hydration or IV hydration groups. Patients who have at least one of the high-risk factors for developing CI-AKI (advanced age, type 2 diabetes mellitus, anemia, hyperuricemia, a history of cardiac failure or systolic dysfunction) were included in the study. All patients had normal renal function or stage 1-2 chronic kidney disease. Patients in the oral hydration group were encouraged to drink unrestricted amounts of fluids freely whereas isotonic saline infusion was performed by the standard protocol in the IV hydration group.

Results: CI-AKI occurred in 8/116 patients (6.9%) in the oral hydration group and 8/109 patients (7.3%) in the IV hydration group (p = 0.89). There was also no statistically significant difference between the two groups when different CI-AKI definitions were taken into account.

Conclusion: Oral hydration is as effective as IV hydration in preventing CI-AKI in patients with normal kidney function or stage 1-2 chronic kidney disease, and who also have at least one of the other high-risk factors for developing CI-AKI.