Nephron Clinical Practice最新文献

High-density lipoprotein cholesterol (HDL-C) contains dozens of apoproteins that participate in normal cholesterol metabolism with a reliance on renal catabolism for clearance from the body. The plasma pool of HDL-C has been an excellent inverse predictor of cardiovascular events. However, when HDL-C concentrations have been manipulated with the use of niacin, fibric acid derivatives, and cholesteryl ester transferase protein inhibitors, there has been no improvement in outcomes in patients where the low-density lipoprotein cholesterol has been well treated with statins. Apolipoprotein L1 (APOL1) is one of the minor apoproteins of HDL-C, newly discovered in 1997. Circulating APOL1 is a 43-kDa protein mainly found in the HDL3 subfraction. In patients with chronic kidney disease (CKD), mutant forms of APOL1 have been associated with rapidly progressive CKD and end-stage renal disease (ESRD). Because mutant forms of APOL1 are more prevalent in African Americans compared to Caucasians, it may explain some of the racial disparities seen in the pool of patients with ESRD in the United States. Thus, HDL-C is an important lipoprotein carrying apoproteins that play roles in vascular and kidney disease.

This position paper critically analyzes the available controlled data regarding biologic therapy in lupus nephritis (LN). Rather than an exhaustive review of all published evidence, the stress is put on the unmet medical needs in LN, the design of trials aimed at testing the effect of a biologic in LN, the possible reasons for LN trial failures and the future of biological therapy in LN.

Background/aims: Lower serum sodium levels have been associated with increased mortality among patients with chronic kidney disease (CKD). Our aim was to analyze the independent factors associated with lower sodium levels among nondialysis patients with advanced CKD and to evaluate the evolution of these patients in comparison to those with higher plasma sodium over a 1-year period.

Methods: We included 72 patients with CKD stages 4 and 5 without clinically evident cardiopathy or liver disease. Bioelectrical impedance and echocardiography were performed to analyze the possible relation between plasma sodium and volume status and subclinical left ventricular (LV) dysfunction. During follow-up, we compared the evolution of patients with lower baseline plasma sodium (low quartile: <138 mEq/l) with that of patients with higher levels over a 1-year period.

Results: At baseline, the independent predictors of lower plasma sodium were C-reactive protein (CRP; OR 0.96; 95% CI 0.91-0.99) and body mass index (OR 0.89; 95% CI 0.78-0.99). An inverse correlation between plasma sodium and CRP was observed (r = -0.32; p = 0.01). Plasma sodium did not correlate with extracellular water and was not different between patients with or without echocardiographic data of LV dysfunction (p = 0.7). During follow-up, patients with lower sodium at baseline showed persistently lower sodium values (p = 0.04), higher CRP (p = 0.05), lower serum albumin (p < 0.01) and higher erythropoietin-stimulating agent resistance index (p = 0.05).

Conclusions: Our results suggest an association between lower plasma sodium and a microinflammatory state among patients with advanced CKD. Inflammation could be an underlying confounding factor explaining the increased mortality in these patients.

Aims: To evaluate the performance of fractional excretion of urea (FeU) for differentiating transient (T) from persistent (P) acute kidney injury (AKI) and to assess performance of FeU in predicting AKI in patients admitted to the ICU.

Methods: We performed secondary analysis of a multicenter prospective observational cohort study on the predictive performance of biological markers for AKI in critically ill patients. AKI was diagnosed according to RIFLE staging.

Results: Of 150 patients, 51 and 41 patients were classified as having T-AKI and P-AKI, respectively. The diagnostic performance for FeU to discriminate T-AKI from P-AKI on the day of AKI was poor (AUC-ROC = 0.61; 95% CI: 0.49-0.73). The diagnostic performance of FeU to predict AKI 1 and 2 days prior to AKI was poor as well (AUC-ROC = 0.61; 95% CI: 0.47-0.74, and 0.58; 95% CI: 0.43-0.73, respectively).

Conclusions: FeU does not seem to be helpful in differentiating T- from P-AKI in critically ill patients and it is a poor predictor of AKI.

Background: Acute kidney injury (AKI) is common in hospitalized patients. Despite the progress that has been made in the last decade, early identification of AKI cases remains a challenge. In recent years, electronic AKI alert (e-AKI alert) systems have been tested and are usually based on changes in serum creatinine (Cr) values. However, these methods do not include one of the common scenarios, i.e. when there is no available preadmission Cr value available for a patient to compare and hence an e-AKI alert cannot be issued. Therefore, it is essential to have an alternative algorithm to produce e-AKI alerts in such scenarios.

Method: We have developed e-AKI alert algorithms which compare serum Cr values at presentation with previous results, within KDIGO AKI guideline-specified classifications. However, where a comparator is not available, we have produced a 'population-based reference Cr value' age and sex matched from 137,000 serum Cr values extracted from blood tests in general practice from our Telepath system.

Results: Cr results were split by gender, and then within each group the Cr were stratified according to year of age. The median Cr for each individual year of age was identified and plotted versus age to give separate graphs for males and females that gave excellent fits (R(2)) to cubic regressions.

Conclusion: Population-based estimated reference Cr measurements from community blood test results is a more robust method of baseline Cr value estimation in generating potential e-AKI alerts to help early recognition and treatment of AKI cases leading to improved outcome.

Background: Heat shock proteins (HSPs) are expressed by cells in response to various environmental stresses. A single-nucleotide polymorphism A+1267G of the HSPA1B gene affects the expression of HSP70-2, with the A allele being protective against inflammatory conditions. We investigated the relation between the HSP A+1267G polymorphism and the clinical outcomes of Chinese peritoneal dialysis (PD) patients.

Methods: We studied 347 new PD cases (181 males, age 56.6 ± 13.7 years). Genotyping was done by standard methods. Patients were followed for 40.5 ± 20.7 months for survival analysis.

Results: For the entire cohort, there was no difference in the 5-year survival between genotype groups. However, there was a significant interaction between HSP polymorphism and diabetic status on the cardiovascular event-free survival. In patients without pre-existing diabetes, 5-year cardiovascular event-free survival of the GG/AG genotype group was significantly better than that of the AA genotype group (57.2 vs. 32.1%, p = 0.011).

Conclusion: The G allele of the HSP70-2 A+1267G polymorphism confers survival advantages in non-diabetic PD patients. The role of HSP in the pathogenesis of cardiovascular disease in renal failure patients needs further investigation.

Background/aims: Haemodialysis causes recurrent haemodynamic stress with subsequent ischaemic end-organ dysfunction. As dialysis prescriptions/schedules can be modified to lessen this circulatory stress, an easily applicable test to allow targeted interventions in vulnerable patients is urgently required.

Methods: Intra-dialytic central venous oxygen saturation (ScvO2) and clinical markers (including ultrafiltration, blood pressure) were measured in 18 prevalent haemodialysis patients.

Results: Pre-dialysis ScvO2 was 63.5 ± 13% and fell significantly to 56.4 ± 8% at end dialysis (p = 0.046). Ultrafiltration volume, a key driver of dialysis-induced myocardial ischaemia, inversely correlated to ScvO2 (r = -0.680, p = 0.015).

Conclusions: This initial study demonstrates ScvO2 sampling is practical, with a potential clinical utility as an indicator of circulatory stress during dialysis.

There is an increasing number of clinical studies suggesting that acute kidney injury (AKI) can be complicated by the onset of progressive renal disease. Indeed, given the frequency of AKI in hospitalized patients, it could potentially be a leading cause of, or contributor to, end-stage renal disease. Insights into the natural history of AKI and potential mechanisms for disease progression can be gleaned from experimental studies. Although such studies underscore the principle that AKI can 'heal with defects', whether ongoing renal disease develops remains a subject of debate. Indeed, in the aftermath of AKI, a variety of secondary renal protective pathways are activated, which may retard or prevent severe chronic kidney disease. Furthermore, the onset of acute uremia per se may exert surprisingly potent renal protective effects. The purpose of this brief report is to review some of the clinical and experimental data that deal with these complex issues.

Background: Toll-like receptors (TLRs) are key players in the innate immune system whose activation leads to an inflammatory response. Inflammation plays an important role in the pathogenesis of chronic kidney disease (CKD) and diabetes mellitus. The aim of our study was to assess the proinflammatory state of nondialysis CKD patients by evaluating the membrane expression of TLR2 and TLR4 and the intracellular IL-1β and IL-6 production in response to the ligand Pam3Cys-Ser-(Lys)4 (Pam3CSK4).

Methods: 85 nondialysis CKD patients [mean estimated glomerular filtration rate: 34 (17-90) ml/min/1.73 m(2)] were divided in 2 groups: 55 nondiabetic CKD patients (CKD group) and 30 patients with diabetic nephropathy (DN group). The two groups were compared with 36 healthy subjects (control group). TLR2 and TLR4 membrane expression in monocytes and Pam3CSK4-induced intracellular production of IL-1β and IL-6 were assessed by flow cytometry.

Results: Both patient groups showed increased TLR2 membrane expression compared with the control group, both at baseline (p < 0.05 for both) and after Pam3CSK4 stimulation (p < 0.05 for both). The DN group exhibited significantly higher TLR4 expression at baseline compared to the CKD and control groups (p < 0.04 and p < 0.02, respectively). Intracellular IL-1β and IL-6 levels at baseline were significantly lower in CKD patients compared to the DN and control groups. After Pam3CSK4 stimulation, intracellular IL-1β and IL-6 increased in all groups, but were lower in the CKD group versus the control group or DN group, which exhibited higher levels than the controls.

Conclusions: Nondialysis CKD patients showed significant alterations in TLR2 and TLR4 membrane expression, and impaired Pam3CSK4-induced cytokine production in monocytes, a phenomenon that is markedly influenced by the presence of diabetes.

An international group of around 50 nephrologists and scientists, including representatives from large dialysis provider organisations, formulated recommendations on how to develop and implement quality assurance measures to improve individual hemodialysis patient care, population health and cost effectiveness. Discussed were methods thought to be of highest priority, those clinical indicators which might be most related to meaningful patient outcomes, tools to control treatment delivery and the role of facilitating computerized expert systems. Emphasis was given to the use of new technologies such as measurement of online dialysance and ways of assessing fluid status. The current evidence linking achievement of quality criteria with patient outcomes was reviewed. This paper summarizes useful processes and quality measures supporting quality assurance that have been agreed across the expert panel. It also notes areas where more understanding is required.