Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients.

Carbamoylation is an important risk factor for accelerated atherogenesis and mortality in patients undergoing hemodialysis (HD). We intended to explore whether carbamoylation as assessed by near-infrared (NIR) analysis of nail proteins is associated with (a) serum concentrations of representative uremic toxins and (b) mortality in HD patients. A total of 53 healthy volunteers and 84 consecutive HD patients were enrolled in this cross-sectional cohort study. Standard laboratory methods were used to measure routine parameters, whereas levels of uremic toxins were determined using reversed-phase high-performance liquid chromatography (RP-HPLC). Spectra of distal fingernail clippings were obtained using an Avantes NIR spectrometer and processed using chemometric data analysis. The second derivative of the peak intensity at 1494 nm attributed to N-H amide bands from NH2 of carbamoyl (-CONH2) groups was higher in HD patients than in control subjects (p < 0.0001). Peak intensity levels were associated with age and plasma levels of representative uremic toxins. Cox-regression analysis revealed a significant association with all-cause mortality, even after adjustment for age. In conclusion, our data revealed that carbamoylation as assessed by NIR analysis of nail proteins is associated with serum concentrations of uremic toxins and also with mortality in HD patients. Further research to explore whether it is a surrogate marker or a hard indicator of mortality risk is warranted.

Binding of bromocresol green and bromocresol purple to albumin in hemodialysis patients.

BACKGROUND: Colorimetric albumin assays based on binding to bromocresol purple (BCP) and bromocresol green (BCG) yield different results in chronic kidney disease. Altered dye binding of carbamylated albumin has been suggested as a cause. In the present study, a detailed analysis was carried out in which uremic toxins, acute phase proteins and Kt/V, a parameter describing hemodialysis efficiency, were compared with colorimetrically assayed (BCP and BCG) serum albumin. METHODS: Albumin was assayed using immunonephelometry on a BN II nephelometer and colorimetrically based on, respectively, BCP and BCG on a Modular P analyzer. Uremic toxins were assessed using high-performance liquid chromatography. Acute phase proteins (C-reactive protein and α1-acid glycoprotein) and plasma protein α2-macroglobulin were assayed nephelometrically. In parallel, Kt/V was calculated. RESULTS: Sixty-two serum specimens originating from hemodialysis patients were analyzed. Among the uremic toxins investigated, total para-cresyl sulfate (PCS) showed a significant positive correlation with the BCP/BCG ratio. The serum α1-acid glycoprotein concentration correlated negatively with the BCP/BCG ratio. The BCP/BCG ratio showed also a negative correlation with Kt/V. CONCLUSIONS: In renal insufficiency, the BCP/BCG ratio of serum albumin is affected by multiple factors: next to carbamylation, uremic toxins (total PCS) and α1-acid glycoprotein also play a role.

Guía de práctica clínica sobre el diagnóstico y tratamiento de la hiponatremia / Hyponatraemia diagnosis and treatment clinical practice guidelines

La hiponatremia se define como una concentración sérica de sodio <135mmol/L y es el trastorno hidroelectrolítico más frecuente en la práctica clínica. La hiponatremia puede causar un amplio espectro de síntomas clínicos, desde sutiles hasta graves o incluso mortales, y se asocia con aumento de la morbimortalidad y prolongación de la estancia hospitalaria. A pesar de ello, el manejo de los pacientes con hiponatremia sigue siendo problemático. La prevalencia de hiponatremia en enfermedades muy diferentes y su manejo por muy diversos especialistas han fomentado la existencia de protocolos de diagnóstico y tratamiento muy diversos, que varían con la especialidad y la institución. La Sociedad Europea de Medicina Intensiva (ESICM), la Sociedad Europea de Endocrinología (ESE) y la Asociación Renal Europea-Asociación Europea de Diálisis y Trasplante (ERA-EDTA), representada por la European Renal Best Practices (ERBP), han desarrollado la guía de práctica clínica sobre el enfoque diagnóstico y tratamiento de la hiponatremia como una empresa conjunta de las 3 sociedades que representan a los especialistas con un interés natural en la hiponatremia, a fin de ofrecer una visión común y holística del abordaje del problema. Además de ofrecer un enfoque riguroso en la metodología y la evaluación de la evidencia, el documento está centrado en resultados importantes para el paciente y en facilitar una herramienta útil para los médicos en la práctica clínica cotidiana. Presentamos ahora una versión abreviada de las recomendaciones y sugerencias sobre el diagnóstico y el tratamiento de la hiponatremia recogidas en la guía complete (AU)

Hyponatremia, defined as a serum sodium concentration <135mmol/l, is the most common water-electrolyte imbalance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from mild to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay. Despite this, the management of hyponatremia patients remains problematic. The prevalence of hyponatremia in a wide variety of conditions and the fact that hyponatremia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and specialty-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed clinical practice guidelines on the diagnostic approach and treatment of hyponatremia as a joint venture of 3 societies representing specialists with a natural interest in hyponatremia. In addition to a rigorous approach to the methodology and evaluation of the evidence, the document focuses on patient-positive outcomes and on providing a useful tool for clinicians involved in everyday practice. In this article, we present an abridged version of the recommendations and suggestions for the diagnosis and treatment of hyponatremia extracted from the full guide (AU)

Management of patients at risk of acute kidney injury.

Acute kidney injury (AKI) is a multifaceted syndrome that occurs in different settings. The course of AKI can be variable, from single hit and complete recovery, to multiple hits resulting in end-stage renal disease. No interventions to improve outcomes of established AKI have yet been developed, so prevention and early diagnosis are key. Awareness campaigns and education for health-care professionals on diagnosis and management of AKI-with attention to avoidance of volume depletion, hypotension, and nephrotoxic interventions-coupled with electronic early warning systems where available can improve outcomes. Biomarker-based strategies have not shown improvements in outcome. Fluid management should aim for early, rapid restoration of circulatory volume, but should be more limited after the first 24-48 h to avoid volume overload. Use of balanced crystalloid solutions versus normal saline remains controversial. Renal replacement therapy should only be started on the basis of hard criteria, but should not be delayed when criteria are met. On the basis of recent evidence, the risk of contrast-induced AKI might be overestimated for many conditions.

Reducing the costs of chronic kidney disease while delivering quality health care: a call to action.

The treatment of chronic kidney disease (CKD) and of end-stage renal disease (ESRD) imposes substantial societal costs. Expenditure is highest for renal replacement therapy (RRT), especially in-hospital haemodialysis. Redirection towards less expensive forms of RRT (peritoneal dialysis, home haemodialysis) or kidney transplantation should decrease financial pressure. However, costs for CKD are not limited to RRT, but also include nonrenal health-care costs, costs not related to health care, and costs for patients with CKD who are not yet receiving RRT. Even if patients with CKD or ESRD could be given the least expensive therapies, costs would decrease only marginally. We therefore propose a consistent and sustainable approach focusing on prevention. Before a preventive strategy is favoured, however, authorities should carefully analyse the cost to benefit ratio of each strategy. Primary prevention of CKD is more important than secondary prevention, as many other related chronic diseases, such as diabetes mellitus, hypertension, cardiovascular disease, liver disease, cancer, and pulmonary disorders could also be prevented. Primary prevention largely consists of lifestyle changes that will reduce global societal costs and, more importantly, result in a healthy, active, and long-lived population. Nephrologists need to collaborate closely with other sectors and governments, to reach these aims.

Fluid Overload in Peritoneal Dialysis Patients.

Volume management in peritoneal dialysis patients is of importance, as both volume overload and dehydration are associated with worse outcomes. When assessing volume status, it is important to understand that different techniques measure different fluid compartments (intracellular vs extracellular vs circulating volume) and the impact of cardiac function. Attention to salt restriction and diuretics can help to maintain euvolemia without need for hypertonic bags. Glycaemia should be monitored to avoid thirst. Dwell length should be adapted to transport status: short dwells for fast transporters, long dwells in slow transporters. The role of bio-compatible solutions on volume control remains controversial.

Renal biopsy in patients with diabetes: a pooled meta-analysis of 48 studies.

Background: The utility of renal biopsy in patients with diabetes is highly debated. Diabetics with rapidly worsening renal disease are often 'clinically' labelled as having diabetic nephropathy (DN), whereas, in many cases, they are rather developing a non-diabetic renal disease (NDRD) or mixed forms (DN + NDRD). Methods: We performed a systematic search for studies on patients with diabetes with data on the frequency of DN, NDRD and mixed forms, and assessed the positive predictive values (PPVs) and odds ratios (ORs) for such diagnoses by meta-analysing single-study prevalence. Possible factors explaining heterogeneity among the different diagnoses were explored by meta-regression. Results: In the 48 included studies ( n = 4876), the prevalence of DN, NDRD and mixed forms ranged from 6.5 to 94%, 3 to 82.9% and 4 to 45.5% of the overall diagnoses, respectively. IgA nephropathy was the most common NDRD (3-59%). PPVs for DN, NDRD and mixed forms were 50.1% [95% confidence interval (CI): 44.7-55.2], 36.9% (95% CI: 32.3-41.8) and 19.7% (95% CI: 16.3-23.6), respectively. The PPV when combining NDRD and mixed forms was 49.2% (95% CI: 43.8-54.5). Meta-regression identified systolic pressure, HbA1c, diabetes duration and retinopathy as factors explaining heterogeneity for NDRD, creatinine and glomerular filtration rate for mixed forms and only serum creatinine for DN. ORs of DN versus NDRD and mixed forms were 1.71 (95% CI: 1.54-1.91) and 4.1 (95% CI: 3.43-4.80), respectively. Conclusions: NDRD are highly prevalent in patients with diabetes. Clinical judgment alone can lead to wrong diagnoses and delay the establishment of adequate therapies. Risk stratification according to individual factors is needed for selecting patients who might benefit from biopsy.

Genetic and clinical factors influence the baseline permeability of the peritoneal membrane.

BACKGROUND: Patients starting peritoneal dialysis (PD) show a significant variability in small solute transport across the peritoneal membrane (PM). The latter parameter determines dialysis prescription and survival. Clinical factors probably influence solute transport across the PM, but the putative role of genetic variants is unknown. METHODS: We have investigated the influence of functional polymorphisms of VEGF, ENOS, and IL-6, together with clinical and biological factors, on baseline peritoneal equilibration test (PET) parameters in a homogeneous population of 152 unrelated Caucasian PD patients from Belgium and the North of France. RESULTS: The distribution of the 21 alleles (7 polymorphisms) and linkage disequilibrium parameters were similar in PD patients and healthy subjects. Univariate and multivariate analyses identified comorbidity, serum albumin, and the -174G/C polymorphism of IL-6 as independent predictors of small solute transport. The -174G/C polymorphism of IL-6 was associated with significantly higher IL-6 mRNA levels in the PM and higher plasma and dialysate IL-6 concentrations, suggesting a dominant effect of the C allele. Patients harboring the CC and GC genotypes (N= 92) were characterized by significantly higher permeability parameters and inflammatory markers than patients harboring the GG genotype (N= 60). In contrast with IL-6, VEGF and ENOS polymorphisms had no influence on baseline peritoneal permeability. CONCLUSION: These data (1) show that, together with clinical parameters, the functionally relevant -174G/C polymorphism of IL-6 contributes to the interpatient variability in small solute transport rate at the start of PD; and (2) substantiate the critical role played by IL-6 in the PM.

An evaluation of an integrative care approach for end-stage renal disease patients.

Studies analyzing the outcome of integrative care of end-stage renal disease (ESRD) patients, whereby patients are transferred from one renal replacement modality to another according to individual needs, are scant. In this study, we analyzed 417 files of 223 hemodialysis (HD) and 194 peritoneal dialysis (PD) patients starting renal replacement therapy between 1979 and 1996, to evaluate the effect of such an approach. Analysis was done for survival of patients on their first modality, for intention-to-treat survival (counting total time on renal replacement therapy, but with exclusion of time on transplantation), and for total survival. Log rank analysis was used and correction for risk factors was performed by Cox proportional hazards regression. Intention-to-treat survival and total survival were not different between PD and HD patients (log rank, P > 0.05). Technique success was higher in HD patients compared to PD patients (log rank, P = 0.01), with a success rate after 3 yr of 61 and 48%, respectively. Thirty-five patients were transferred from HD to PD and 32 from PD to HD. Transfer of PD patients to HD was accompanied by an increase in survival compared to those remaining on PD (log rank, P = 0.001), whereas, in contrast, transfer of patients from HD to PD was not (log rank, P = 0.17). Survival of patients remaining more than 48 mo on their initial modality was lower for PD patients (log rank, P < 0.01). A matched-pair analysis between patients who started on PD and who were transferred to HD later (by definition called integrative care patients), and patients who started and remained on HD, showed a survival advantage for the integrative care patients. These results indicate that patient outcome is not jeopardized by starting patients on PD, at least if patients are transferred in a timely manner to HD when PD-related problems arise.