Search

A global rise in the prevalence of patients with chronic kidney disease (CKD) with end-stage kidney disease (ESKD) has led to a considerable and increasing burden to health systems, patients, and society. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are proven to reduce incidence of cardio-renal outcomes, including onset of ESKD. Recent post hoc analyses of SGLT2 inhibitor trials extrapolate substantial delays in the average time to ESKD over a patient's lifetime. In this article, we explore the possible real-world effects of such a delay by considering the available evidence reporting outcomes following onset of ESKD. From the patient perspective, a delay in reaching ESKD could substantially improve health-related quality of life and result in additional life years without the need for kidney replacement therapies, a target relevant to all CKD subpopulations. Furthermore, should a patient initiate dialysis at an older age as a result of CKD progression, the time spent in receipt of dialysis, and therefore associated healthcare costs, may also be reduced. A delay in progression may also lead to changes in the management of ESKD, such as increased election of conservative care in preference to dialysis, particularly in elderly populations. For younger patients with CKD, those who reach ESKD while employed face considerable work impairment and productivity loss, as may families and care partners of working age. Therefore, a delay to the onset of ESKD will reduce the proportion of their working lives affected by productivity losses or unemployment due to medical reasons. In conclusion, optimised treatment of CKD may lead to a shift in treatment options, but proper and timely implementation is essential for the realisation of improved outcomes., (© 2024. The Author(s).)

Background: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level., Methods: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200-5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes., Results: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%) in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211-0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49--0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heart failure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placebo in all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories, respectively)., Conclusions: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. Methods and Results We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m 2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin-angiotensin-aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin-angiotensin-aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β-adrenergic antagonists (39.0%), diuretics (43.7%), and antithrombotic (47.4%), and lipid-lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. Conclusions The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications. Registration Information clinicaltrials.gov. Identifier: NCT03036150.

Unassigned: Kidney replacement therapy (KRT) initiated in Latin America towards the second half of the 20th century, starting with dialytic therapies and, shortly thereafter, with kidney transplant. By the end of 2021, close to half a million Latin Americans were under KRT, with an overall unadjusted prevalence of 872 per million persons (pmp), yet with significant heterogeneity between nations. By treatment modality, 68% of prevalent patients were treated with hemodialysis (HD), 9% with peritoneal dialysis (PD), and 23% were living with a functioning kidney graft (LFG). In the last decade, HD is the KRT that has had the largest growth, and it also has incorporated newer and better technologies. Nevertheless, Latin America shows heterogeneity between countries, and as a region we are far from achieving full accessibility to all in need of KRT. While there has been growth and improvement in existing renal dialysis registries, and several countries that did not previously have these registries have implemented them, there are still some nations with limited or absent registry implementation. The number of nephrologists in the region is heterogeneous, with only four countries having an appropriate group of specialists. The remaining nations have an important need to expand nephrology training programs. SLANH is a major regional player in addressing these topics and supporting the expansion of appropriate nephrology programs to improve inequalities and patient care. (Rev Invest Clin. 2023;75(6):300-8)., (Copyright: © 2023 Permanyer.)

Aims: Dapagliflozin was approved for use in patients with chronic kidney disease (CKD) based on results of the DAPA-CKD trial, demonstrating attenuation of CKD progression and reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard therapy. The study objective was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes across 31 countries and regions., Materials and Methods: A comparative cost-determination framework estimated outcome-related costs of dapagliflozin plus standard therapy versus standard therapy alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (HHF), acute kidney injury (AKI), and ACM were estimated for a treated population of 100,000 patients. Associated medical care costs for non-fatal events were calculated using sources from a review of publicly available data specific to each considered setting., Results: Patients treated with dapagliflozin plus standard therapy experienced fewer incidents of ESKD (7,221 vs 10,767; number needed to treat, NNT: 28), HHF (2,370 vs 4,684; NNT: 43), AKI (4,110 vs. 5,819; NNT: 58), and ACM (6,383 vs 8,874; NNT: 40) per 100,000 treated patients versus those treated with standard therapy alone. Across 31 countries/regions, reductions in clinical events were associated with a 33% reduction in total costs, or a cumulative mean medical care cost offset of $264 million per 100,000 patients over 3 years., Limitations and Conclusions: This analysis is limited by the quality of country/region-specific data available for medical care event costs. Based on the DAPA-CKD trial, we show that treatment with dapagliflozin may prevent cardio-renal event incidence at the population level, which could have positive effects upon healthcare service delivery worldwide. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management.

Introduction: Expanded hemodialysis (HDx) is expected to provide enhanced permeability of medium-sized molecules, selective solute retention, and better internal retrofiltration. The primary objective of this study was to compare the efficiency for removal of β2-microglobulin with 3 different extracorporeal therapies (ETs): high-flux hemodialysis (HF), online hemodiafiltration (OL-HDF), and HDx. The secondary objective was to evaluate the efficiency of removal of other uremic toxins, including urea, phosphate, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-cresol., Methods: This single-center, randomized, and cross-over study was performed. Patients were randomized to determine the initial modality of treatment, each period lasted 4 weeks and between one modality and another, there was a washout period of 1 week. Reduction ratios (RRs) of different-size molecules and albumin were calculated for the different ET., Results: Twenty-two patients were included, β2-microglobulin RR was greater during both OL-HDF and HDx as compared to HF (RR 62% vs. 73% vs. 27%, respectively, p = <0.0001), and there was no significant difference between HDx and OL-HDF (p = 0.09). A decrease in serum phosphate levels was observed in the HDx and OL-HDF periods, contrary to an increase in HF (-0.79 mg/dL vs. -1.02 mg/dL vs. + 0.11 mg/dL, respectively, p = <0.0001). There was no difference in RRs of other molecules (BUN, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-Cresol). There was no decrease in serum albumin in any ET., Conclusion: HDx provides enhanced removal of β2-microglobulin and phosphate as compared to HF, and similar efficacy as with OL-HDF. HDx should be considered an alternative to chronic convective therapies., (© 2023 S. Karger AG, Basel.)

Aims/hypothesis: In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin reduced the risks of progressive kidney disease, hospitalised heart failure or cardiovascular death, and death from all causes in patients with chronic kidney disease (CKD) with or without type 2 diabetes. Patients with more severe CKD are at higher risk of kidney failure, cardiovascular events and all-cause mortality. In this post hoc analysis, we assessed the efficacy and safety of dapagliflozin according to baseline Kidney Disease Improving Global Outcomes (KDIGO) risk categories., Methods: DAPA-CKD was a double-blind, placebo-controlled trial that randomised patients with an eGFR of 25-75 ml min -1 [1.73 m] -2 and urinary albumin/creatinine ratio (UACR) of ≥22.6 and <565.0 mg/mmol (200-5000 mg/g) to dapagliflozin 10 mg/day or placebo. The primary endpoint was a composite of ≥50% reduction in eGFR, end-stage kidney disease (ESKD), and death from a kidney or cardiovascular cause. Secondary endpoints included a kidney composite (≥50% reduction in eGFR, ESKD and death from a kidney cause), a cardiovascular composite (heart failure hospitalisation or cardiovascular death), and death from all causes. We used Cox proportional hazards regression analyses to assess relative and absolute effects of dapagliflozin across KDIGO risk categories., Results: Of the 4304 participants in the DAPA-CKD study, 619 (14.4%) were moderately high risk, 1349 (31.3%) were high risk and 2336 (54.3%) were very high risk when categorised by KDIGO risk categories at baseline. Dapagliflozin reduced the hazard of the primary composite (HR 0.61; 95% CI 0.51, 0.72) and secondary endpoints consistently across KDIGO risk categories (all p for interaction >0.09). Absolute risk reductions for the primary outcome were also consistent irrespective of KDIGO risk category (p for interaction 0.26). Analysing patients with and without type 2 diabetes separately, the relative risk reduction with dapagliflozin in terms of the primary outcome was consistent across subgroups of KDIGO risk categories. The relative frequencies of adverse events and serious adverse events were also similar across KDIGO risk categories., Conclusion/interpretations: The consistent benefits of dapagliflozin on kidney and cardiovascular outcomes across KDIGO risk categories indicate that dapagliflozin is efficacious and safe across a wide spectrum of kidney disease severity., Trial Registration: ClinicalTrials.gov NCT03036150., Funding: The study was funded by AstraZeneca., (© 2022. The Author(s).)

Objective: This study aimed to compare the effect of the use of a renal-specific oral nutritional supplement (RS-ONS) during hemodialysis sessions and the use of RS-ONS at home on the incidence of intradialytic hypotension., Methods: A single-center, 12-week, open-label, randomized controlled clinical trial was conducted. The intervention was a RN-ONS divided into two portions: 100 and 137 mL. The first portion was given after 1 hour of hemodialysis (HD) treatment, while the second portion was given 45 minutes before the end of HD. The research staff registered the baseline and final nutritional parameters and systolic arterial pressure (SAP) from the screen of the HD device during 36 HD sessions. Hypotension symptoms were also recorded every hour during each HD session. The nutritional and functional status was also assessed., Results: We registered a total of 16 hypotensive events during 1082 HD sessions: 9 were in patients supplemented at home (551 HD sessions) and 7 occurred in patients supplemented during HD P = .668. Incidence of intradialytic hypotension (IH) during 1082 HD sessions was 1.4%. The total malnutrition inflammation score (MIS) decreased in both groups (P < .01), and the percentage of cachexia improved in the supplemented-during-HD group (P < .05)., Conclusions: In this randomized controlled trial, intradialytic hypotension events did not increase with the RS-ONS during HD treatment. This strategy appears to be a safe anabolic nutritional strategy for the prevention of PEW, selecting stable patients and administering a fractioned volume of the supplement after the first hour of HD treatment. More studies with larger samples size are required to confirm these findings., (Copyright © 2021. Published by Elsevier Inc.)

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause., Methods: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1·73m 2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150., Findings: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0-2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52-0·79) and those without diabetes (0·50, 0·35-0·72; p interaction =0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45-0·73] vs 0·51 [0·34-0·75]; P interaction =0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53-0·92] vs 0·79 [0·40-1·55]; P interaction =0·78), and all-cause mortality (0·74 [0·56-0·98] vs 0·52 [0·29-0·93]; P interaction =0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51-0·78), glomerulonephritides (n=695; 0·43, 0·26-0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44-1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29-1·19; P interaction =0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes., Interpretation: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease., Funding: AstraZeneca., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: A recently recognised form of chronic kidney disease (CKD) of unknown origin (CKDu) is afflicting communities, mostly in rural areas in several regions of the world. Prevalence studies are being conducted in a number of countries, using a standardised protocol, to estimate the distribution of estimated glomerular filtration rate (eGFR), and thus identify communities with a high prevalence of reduced glomerular filtration rate (GFR). In this paper, we propose a standardised minimum protocol for cohort studies in high-risk communities aimed at investigating the incidence of, and risk factors for, early kidney dysfunction., Methods and Analysis: This generic cohort protocol provides the information to establish a prospective population-based cohort study in low-income settings with a high prevalence of CKDu. This involves a baseline survey that included key elements from the DEGREE survey (eg, using the previously published DEGREE methodology) of a population-representative sample, and subsequent follow-up visits in young adults (without a pre-existing diagnosis of CKD (eGFR<60 mL/min/1.73m 2 ), proteinuria or risk factors for CKD at baseline) over several years. Each visit involves a core questionnaire, and collection and storage of biological samples. Local capacity to measure serum creatinine will be required so that immediate feedback on kidney function can be provided to participants. After completion of follow-up, repeat measures of creatinine should be conducted in a central laboratory, using reference standards traceable to isotope dilution mass spectrometry (IDMS) quality control material to quantify the main outcome of eGFR decline over time, alongside a description of the early evolution of disease and risk factors for eGFR decline., Ethics and Dissemination: Ethical approval will be obtained by local researchers, and participants will provide informed consent before the study commences. Participants will typically receive feedback and advice on their laboratory results, and referral to a local health system where appropriate., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: It is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO)., Methods: Retrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the "Malnutrition Inflammation Score" (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value < 0.05 as statistically significant., Results: Sixty-one patients ended the follow up. Both groups were similar in basal hemoglobin, hematocrit and other hematopoiesis markers (p = NS). Patients without PEW have a decrease risk for poor response to treatment with EPO (RR = 0.562 [95% CI, 0.329-0.961-]) than those with PEW. Finally, hemoglobin concentrations were evaluated at baseline and every four weeks until week 12, finding a statistically significant improvement only in patients without PEW according MIS (p < 0.05)., Conclusions: PEW is an incremental predictor of poor responsiveness to EPO in HD patients, thus, it is important to consider correcting malnutrition or wasting for a favorable response to treatment with EPO.

Aims: Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin-to-creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit., Materials and Methods: SONAR is a randomized, double-blind, placebo-controlled trial with approximately 3500 participants who have stage 2-4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin-angiotensin system inhibitor., Results: After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with <30% UACR reduction (non-responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end-stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05)., Conclusion: SONAR aims to determine whether atrasentan added to guideline-recommended therapies safely reduces the risk of CKD progression and delays the onset of end-stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial "surrogate" response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Gastrointestinal symptoms (GIS) are common in patients with end-stage renal disease (ESRD) and are associated with nutritional risks resulting from low food intake. Little is known about the relationship between GIS and malnutrition in geriatric patients with ESRD. The main objective of this study was to determine the relationship between nutritional status and severity of GIS in geriatric patients on dialysis therapy. Clinically-stable geriatric patients (older than 60 years old) who were dialysis outpatients were included in this cross-sectional study. The severity of GIS was assessed using the Gastrointestinal Symptoms Questionnaire (GSQ, short version), with patients classified into three groups: mild, moderate, and severe. Nutritional status was evaluated with the Malnutrition Inflammation Score (MIS), anthropometric assessment, biochemical parameters, and bioelectrical impedance. Descriptive statistics were used and differences between groups were analyzed with ANOVA and Kruskal Wallis, with a p < 0.05 considered to indicate significance. Fifty patients completed the study; the median age was 67 years old. Twenty-three patients were on hemodialysis (HD) and 27 were on peritoneal dialysis (PD). No significant differences were found according to dialysis modality, presence of diabetes, or gender. Ninety percent of patients had at least one GIS. Poorer nutritional status (evaluated by MIS) was related to a higher severity of GIS. There were no significant differences with other nutritional parameters. Our study showed a high prevalence of GIS in geriatric patients. There were no differences in observed GIS values that were attributed to dialysis modality, gender, or presence of type 2 diabetes mellitus (DM2). Severe GIS values were associated with poorer nutritional status determined by MIS, however, there was no association with anthropometry, biochemical values, or bioimpedance vector analysis., Competing Interests: The authors declare no conflict of interest.

Background: End-stage renal disease and its treatment have a negative impact on the quality of life of patients., Objective: To determine the clinical, dialytic, and laboratory factors associated with poor health-related quality of life in Mexican patients on hemodialysis., Methods: A multicenter, cross-sectional study. The KDQOL-SF36 v1.3 questionnaire was applied to patients with end-stage renal disease on hemodialysis in different regions of Mexico. Patients were classified according to their overall score on the questionnaire: poor health-related quality of life (overall score below the median) or good health-related quality of life (overall score above the median). Clinical, dialytic, and laboratory variables associated with poor health-related quality of life were analyzed using linear correlation and multivariate logistic regression., Results: We included 194 adult patients with a median age of 55 (45-64) years. The diagnosis of poor health-related quality of life was present in 47.4% of patients. A poor correlation was found between the clinical, dialytic, and biochemical parameters and the health-related quality of life score (range of correlations r = -0.4 to 0.2). Serum albumin level showed the highest number of weak, statistically significant correlations. Factors associated with poor health-related quality of life in the multivariate analysis were: time spent on hemodialysis (OR = 1.02; 95% CI; 1.00-1.04; p = 0.02), use of a venous catheter (OR = 3.2; 95% CI: 1.36-7.75; p = 0.01), and serum albumin < 4 g/dl (OR = 3.55; 95% CI: 1.44-8.74; p < 0.01)., Conclusions: Poor health-related quality of life was common in Mexican patients undergoing hemodialysis. No strong correlation was found between the clinical, dialytic, or laboratory factors with health-related quality of life. Factors associated with poor health-related quality of life were: time on hemodialysis, use of a venous catheter, and serum albumin level < 4 g/dl.

Unlabelled: ♦, Background: Vascular calcification is strongly associated with cardiovascular disease and mortality. However, some factors related to vascular calcification in patients with end-stage renal disease receiving peritoneal dialysis (PD) remain unknown. This study aimed to evaluate the associations of osteoprotegerin (OPG), osteopontin (OPN), osteocalcin (OCN), fibroblast growth factor 23 (FGF-23), magnesium, and phosphate clearance with vascular calcification in PD subjects, assessed by plain radiographs. ♦, Methods: Simple vascular calcification scores (SVCS) obtained from plain X-rays of the pelvis and hands, and the Kauppila Index (KI) from lateral lumbar X-rays were assessed in 76 adults receiving PD for ≥ 6 months (43 women, median age 39 years, median time on PD 1.4 years). Levels of OPG, OPN, OCN, and FGF-23 were determined by luminometry. ♦, Results: Serum OPG levels were higher in subjects with vascular calcification (n = 22 with SVCS > 3; n = 19 with KI > 7) compared with those with less calcification (p < 0.001). Spearman's correlation coefficients between OPG and SVCS and KI were r = 0.49 and r = 0.51, respectively (both p < 0.001). Subjects with vascular calcification had significantly lower renal phosphate clearance. Multiple regression analysis showed that vascular calcification assessed by SVCS was associated with age (r = 0.2, p = 0.042), diabetes mellitus (r = 2.4, p < 0.001), body mass index (BMI) (r = 0.09, p = 0.037), and OPG (r = 0.22, p = 0.001). Vascular calcification assessed by KI was associated with age (r = 0.16, p < 0.001), time on PD (r = 0.54, p = 0.001) and OPG (r = 0.08, p = 0.04). Osteocalcin, OPN, FGF-23, and magnesium were not associated with vascular calcification. ♦, Conclusions: Higher levels of OPG were consistently associated with vascular calcification in subjects on PD., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%., (Copyright © 2015 by the American Society of Nephrology.)

Background and Objectives: The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥65 years, n=1005) and younger (<65 years, n=2878) patients., Design, Setting, Participants, & Measurements: Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified., Results: Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were >3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups., Conclusions: In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone., (Copyright © 2015 by the American Society of Nephrology.)

Background: Premature cardiovascular disease limits the duration and quality of life on long-term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial., Methods and Results: EVOLVE was a randomized, double-blind, placebo-controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance., Conclusions: Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes., Clinical Trials Registration: Unique identifier: NCT00345839. URL: ClinicalTrials.gov., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Anemia almost invariably occurs in patients with chronic kidney disease. Limited data are available regarding anemia management in Latin American (LA) hemodialysis (HD) patients., Objective: To evaluate the results of the first anemia survey of the Anemia Committee of the SLANH., Methods: This is a multinational, voluntary survey that collected anemia management data from adult HD patients from independent, non-chain owned HD units, between 09/2009 and 03/2010. T-test, ANOVA, chi-square test and multivariate logistic regression were used for statistical analysis., Results: The survey received responses from 134 HD units of 16 countries providing data from 9,025 patients. Mean values of Hb, ferritin, and transferrin saturation (TSAT) were 10.5 ± 1.8 g/dL, 570 ± 539 µg/l, and 29.8 ± 15%, respectively. Only 32.7% of patients were within the Hb target of 10.5-12.0 g/dL (46.3% were below and 21.1% above). Erythropoietin-stimulating agents (ESAs) were administered to 84.3% patients and 68.3% received intravenous iron (IV). Iron deficiency (TSAT≤20%) was present in 27.5% patients and among those receiving erythropoietin, 47% did not achieve Hb target. The independent variables associated with the lowest Hb level (<10.5 g/dL) were: female gender, TSAT<25% and age<50 years., Conclusions: According to these results, nearly half of LA chronic HD patients did not achieve the recommended Hb target despite wide use of ESAs and IV iron.

Context: The clinical course of secondary hyperparathyroidism (sHPT) in patients on hemodialysis is not well described, and the effect of the calcimimetic cinacalcet on disease progression is uncertain., Objective: Our objective was to describe 1) the clinical course of sHPT in patients treated with phosphate binders and/or vitamin D sterols and 2) the impact of cinacalcet on the occurrence of severe unremitting HPT, defined by the persistence of markedly elevated PTH concentrations together with hypercalcemia or parathyroidectomy (PTX)., Design and Setting: This was a randomized, double-blind, placebo-controlled, global, multicenter clinical trial., Patients: Of 5755 patients screened with moderate to severe sHPT, 3883 patients on hemodialysis were included in the trial., Main Outcome Measures: Outcomes included PTX; severe, unremitting HPT; and use of commercial cinacalcet (a protocol violation)., Intervention: Intervention was cinacalcet (30-180 mg daily) or placebo for up to 64 months., Results: In the 1935 patients randomized to placebo, 278 patients (14%) underwent PTX (median PTH 1872 pg/mL within the previous 12 weeks from surgery). Age, sex, geographic region, co-morbidity, calcium-containing phosphate binder use, and baseline serum calcium, phosphorus, and PTH concentrations were associated with PTX. Commercial cinacalcet was started in 443 (23%) patients (median PTH 1108 pg/mL before treatment began). Severe unremitting HPT developed in 470 patients (24%). In a multivariable Cox model, the relative hazard (comparing patients randomized to cinacalcet versus placebo) of severe unremitting HPT was 0.31 (95% confidence interval = 0.26-0.37). The relative hazard differed little when adjusted by baseline clinical characteristics., Conclusions: Severe unremitting HPT develops frequently in patients on hemodialysis despite conventional therapy, and cinacalcet substantially reduces its occurrence.

Background: Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients., Methods: In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle., Results: The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet., Conclusions: In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

Background: Secondary hyperparathyroidism (sHPT) and other abnormalities associated with chronic kidney disease-mineral bone disorder can contribute to dystrophic (including vascular) calcification. Dietary modification and variety of medications can be used to attenuate the severity of sHPT. However, it is unknown whether any of these approaches can reduce the high risks of death and cardiovascular disease in patients with end-stage renal disease., Methods: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial was designed to test the hypothesis that treatment with the calcimimetic agent cinacalcet compared with placebo (on a background of conventional therapy including phosphate binders +/- vitamin D sterols) reduces time to death or non-fatal cardiovascular events (specifically myocardial infarction, unstable angina, heart failure and peripheral arterial disease events) among patients on hemodialysis with sHPT. This report describes baseline characteristics of enrolled subjects with a focus on regional variation., Results: There were 3883 subjects randomized from 22 countries, including the USA, Canada, Australia, three Latin American nations, Russia and 15 European nations. The burden of overt cardiovascular disease at baseline was high (e.g. myocardial infarction 12.4%, heart failure 23.3%). The median plasma parathyroid hormone concentration at baseline was 692 pg/mL (10%, 90% range, 363-1694 pg/mL). At baseline, 87.2% of subjects were prescribed phosphate binders and 57.5% were prescribed activated vitamin D derivatives. Demographic data, comorbid conditions and baseline laboratory data varied significantly across regions., Conclusions: EVOLVE enrolled 3883 subjects on hemodialysis with moderate to severe sHPT. Inclusion of subjects from multiple global regions with varying degrees of disease severity will enhance the external validity of the trial results.

Importance of the Field: Patients with chronic kidney disease (CKD) have an increased prevalence and incidence of cardiovascular events. In predialysis stages as well as in end-stage renal disease (ESRD), mortality in patients with chronic renal failure is most frequently due to cardiovascular disease., Areas Covered in the Review: This review examines the prevalence and incidence of cardiovascular disease in the different stages of CKD, summarizes risk factors of cardiovascular disease (CVD) in patients with reduced renal function and examines treatment strategies in nontraditional risk factors and lifestyle modifications of importance in patients with CKD., What the Reader Will Gain: The reader will be brought up to date with the relative contribution of traditional and nontraditional risk factors of cardiovascular disease in CKD patients., Take Home Message: Lifestyle modifications, including weight control, cessation of smoking and dietary salt restriction, are measures that should have a major impact in the cardiovascular morbidity and mortality in patients with CKD. Additional benefit may be gained by treating nontraditional cardiovascular risk factors that are characteristic of chronic renal failure.

Severe uremia is now a rare occurrence in most developed nations, and yet is still present in many countries of the world. It includes clinical manifestations such as calciphylaxis and uremic frost, which are now rarely seen. Patients with extremely high levels of blood urea nitrogen (above 175 mg/dL) are at a higher risk of experiencing first-time hemodialysis-related complications, in particular dialysis disequilibrium syndrome (DDS). DDS is a central nervous disorder characterized by a wide variety of neurological symptoms that range from nausea and vomiting to even death due to cerebral edema. There are 2 main theories to explain its pathophysiology: the reverse urea effect, which considers that the shift of urea between brain intracellular space and plasma is not immediate, causing a higher concentration of urea within the brain and leading to cerebral edema. The second theory considers that after hemodialysis, patients have transient paradoxical metabolic acidosis within the central nervous system, displacing Na(+) and K(+) from organic anions, making them osmotically active and again leading to cerebral edema. The main goal is to prevent the occurrence of DDS, for which there are several proposed measures including continuous renal replacement therapies. Once established, treatment should be focused on supportive therapy. Another uncommon phenomenon described in patients who initiate hemodialysis is transient pulmonary leukocyte margination, which in conjunction with an inflammatory milieu, may lead to non-cardiogenic pulmonary edema. We present the case of a young adult with severe uremia who, despite application of recommended measures, developed DDS and non-cardiogenic pulmonary edema.

Background and Objectives: Natriuretic peptides have been suggested to be of value in risk stratification in dialysis patients. Data in patients on peritoneal dialysis remain limited., Design, Setting, Participants, & Measurements: Patients of the ADEMEX trial (ADEquacy of peritoneal dialysis in MEXico) were randomized to a control group [standard 4 x 2L continuous ambulatory peritoneal dialysis (CAPD); n = 484] and an intervention group (CAPD with a target creatinine clearance > or =60 L/wk/1.73 m(2); n = 481). Natriuretic peptides were measured at baseline and correlated with other parameters as well as evaluated for effects on patient outcomes., Results: Control group and intervention group were comparable at baseline with respect to all measured parameters. Baseline values of natriuretic peptides were elevated and correlated significantly with levels of residual renal function but not with body size or diabetes. Baseline values of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) but not proANP(1-30), proANP(31-67), or proANP(1-98) were independently highly predictive of overall survival and cardiovascular mortality. Volume removal was also significantly correlated with patient survival., Conclusions: NT-proBNP have a significant predictive value for survival of CAPD patients and may be of value in guiding risk stratification and potentially targeted therapeutic interventions.

In recent decades, Latin America (LA) has experienced profound demographic and epidemiologic changes conditioning an enormous increase in prevalence and incidence of chronic non-communicable diseases. End-stage renal disease has steadily increased in prevalence and incidence (478.2 and 168.7 pmp, respectively) and is emerging as a devastating medical, social, and economic problem for patients, families, and national health systems. The development of successful renal replacement treatment modalities has emphasized the wide breach in healthcare between developed and emerging nations. LA is composed of many nations that have a common social and cultural background yet exhibit significant variations in socioeconomic status, ethnicities, and human development. In addition, the region is experiencing a type 2 diabetes mellitus epidemic and a constant growth of related end-stage renal disease which at present is not sustainable and will be unaffordable in most countries, unless changes in public health policy and a new focus on the problem is generated. Renal transplantation, though increasing, cannot revert the growing prevalence. The development of public health policies and prevention programs is mandatory in LA and requires a better knowledge of prevalence and distribution of risk factors in the different nations of the region., ((c) 2008 S. Karger AG, Basel.)

Representatives from 19 Latin American countries gathered to report and deliberate on both the present and future implications of the growing epidemic of chronic kidney disease-as well as cardiovascular disease, diabetes, and hypertension-and to define the role that national health systems need to adopt in order to cope with them. Country-by-country reports provided an excellent overview of the current state of health care in general and chronic diseases in particular. The meeting concluded with a consensus statement on the most urgent needs for the next decade.

Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type 2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation. Alarmed by the immense challenge to human morbidity and the economic burden of CKD and ensuing systemic cardiovascular disease, the International Society of Nephrology convened a multidisciplinary group of expert physicians and public health leaders from around the world to develop strategies to delay and avert this bleak future by effective prevention of CKD based on awareness, early detection, and effective treatment.

Background: This study aims to compare serum C-reactive protein (CRP), interleukin (IL-6), and tumor necrosis factor (TNF)-alpha in end-stage renal disease (ESRD) patients before versus after receiving renal transplantation (RT) and versus donors., Methods: Serum samples from 37 ESRD patients (24 male, age 34+/-13 years) were collected before and after RT; in addition, samples from 31 donors were obtained at transplantation. CRP concentrations were measured using nephelometry, and TNF-alpha and IL-6 were measured by enzyme-linked immunoadsorbent assay., Results: Ninety-two percent of recipients had a living donor, 73% received cyclosporine A, 27% tacrolimus, and 70% induction with daclizumab. Thirteen percent had acute rejection and 16% chronic allograft nephropathy. All inflammation markers decreased 6 months after RT, but only CRP was below baseline values (baseline: 5.0+/-3.5; 6 months: 3.0+/-0; 12 months: 3.2+/-0.7; 18 months: 3.2+/-0.6; donors: 3.6+/-1.5 mg/L; P<0.05), whereas median TNF-alpha (baseline: 0.1 [0.03-0.2]; 6 months: 0 [0-0.1]; 12 months: 0.3 [0.1-2.6]; 18 months: 0.6 [0.1-1.9]; donors: 0 [0-0.1] pg/mL; P<0.05) and IL-6 (baseline: 1.9 [1.2-7.1]; 6 months: 1.2 [0.6-28.3]; 12 months: 2.6 [1.3-3.4]; 18 months: 2.7 [1.7-4.2]; donors: 1.1 [0.6-1.9] pg/mL; P<0.05) significantly increased up to the end of follow-up. Before RT, CRP correlated with age (r 0.45, P=0.006) and albumin (r -0.36, P=0.04). TNF-alpha and IL-6 were correlated before (r 0.34, P=0.04) and after (r 0.55, P=0.02) RT. Inflammation markers were not different in patients who had acute rejection episodes or chronic nephropathy., Conclusions: Compared with controls, patients displayed an inflammatory phenomenon before receiving RT. Serum CRP decreased significantly after RT, whereas TNFalpha and IL-6 increased.

It has been shown that reactive oxygen species are involved in chronic puromycin aminonucleoside (PAN) induced nephrotic syndrome (NS) and that a 20% soy protein diet reduces renal damage in this experimental model. The purpose of the present work was to investigate if a 20% soy protein diet is able to modulate kidney nitrotyrosine formation and the activity of renal antioxidant enzymes (catalase, glutathione peroxidase, Cu,Zn- or Mn-superoxide dismutase) which could explain, at least in part, the protective effect of the soy protein diet in rats with chronic NS induced by PAN. Four groups of rats were studied: (1) Control rats fed 20% casein diet, (2) Nephrotic rats fed 20% casein diet, (3) Control rats fed 20% soy protein diet, and (4) Nephrotic rats fed 20% soy protein diet. Chronic NS was induced by repeated injections of PAN and rats were sacrificed at week nine. The soy protein diet ameliorated proteinuria, hypercholesterolemia, and the increase in serum creatinine and blood urea nitrogen observed in nephrotic rats fed 20% casein diet. Kidney nitrotyrosine formation increased in nephrotic rats fed 20% casein diet and this increase was ameliorated in nephrotic rats fed 20% soy protein diet. However, the soy protein diet was unable to modulate the antioxidant enzymes activities in control and nephrotic rats fed 20% soy protein diet. Food intake was similar in the two diet groups. The protective effect of a 20% soy protein diet on renal damage in chronic nephropathy induced by PAN was associated with the amelioration in the renal nitrotyrosine formation but not with the modulation of antioxidant enzymes.

Background: The prognosis and outcome in patients with end stage renal disease is significantly related to the predialysis care and early or late nephrological referral. Late nephrological referral has been associated with more hospital admissions and mortality at six months after the dialysis was initiated. We lack information about the role of early nephrological referral and its impact in biochemical variables and first hospitalization in our country., Methods: The charts of all patients that were admitted to peritoneal dialysis in the period 01/1999-06/2001 were reviewed. We divided the population in group A with patients referred to nephrologist more than 3 months before the start of dialysis (early referral) and group B with those patients referred for a period shorter than three months or no referred before the start of dialysis (late referral or no referral). The patient's characteristics, laboratory values, characteristics of the first hospitalization and drugs were analyzed when dialysis was initiated and after six months of follow-up., Results: Patients in group A were older and the percentage of patients with diabetes and hypertension was higher. The patients with early referral started dialysis with higher levels of hemoglobin (9.2 vs. 8.3 g/dL, p = 0.01) and with lower serum levels of BUN (91 vs. 122.5 mg/dL, p = 0.0001), creatinine (8.4 vs. 12.8 mg/dL, p = 0.0002) and phosphorus (6.4 vs. 7.7 mg/dL, p = 0.01). The length of the first hospitalization was shorter in patients of Group A (5.7 vs. 10.5 days, p = 0.004) and the emergency department was less used to peritoneal catheter placement in this group (46.3 vs. 86.9%, p = 0.01). There were not differences in hospitalization between the two groups after six months., Conclusion: Patients with early referral to a nephrologist show better biochemical variables, shorter first hospitalization length and higher percentage of elective placement of catheter.

Small-solute clearance targets for peritoneal dialysis (PD) have been based on the tacit assumption that peritoneal and renal clearances are equivalent and therefore additive. Although several studies have established that patient survival is directly correlated with renal clearances, there have been no randomized, controlled, interventional trials examining the effects of increases in peritoneal small-solute clearances on patient survival. A prospective, randomized, controlled, clinical trial was performed to study the effects of increased peritoneal small-solute clearances on clinical outcomes among patients with end-stage renal disease who were being treated with PD. A total of 965 subjects were randomly assigned to the intervention or control group (in a 1:1 ratio). Subjects in the control group continued to receive their preexisting PD prescriptions, which consisted of four daily exchanges with 2 L of standard PD solution. The subjects in the intervention group were treated with a modified prescription, to achieve a peritoneal creatinine clearance (pCrCl) of 60 L/wk per 1.73 m(2). The primary endpoint was death. The minimal follow-up period was 2 yr. The study groups were similar with respect to demographic characteristics, causes of renal disease, prevalence of coexisting conditions, residual renal function, peritoneal clearances before intervention, hematocrit values, and multiple indicators of nutritional status. In the control group, peritoneal creatinine clearance (pCrCl) and peritoneal urea clearance (Kt/V) values remained constant for the duration of the study. In the intervention group, pCrCl and peritoneal Kt/V values predictably increased and remained separated from the values for the control group for the entire duration of the study (P < 0.01). Patient survival was similar for the control and intervention groups in an intent-to-treat analysis, with a relative risk of death (intervention/control) of 1.00 [95% confidence interval (CI), 0.80 to 1.24]. Overall, the control group exhibited a 1-yr survival of 85.5% (CI, 82.2 to 88.7%) and a 2-yr survival of 68.3% (CI, 64.2 to 72.9%). Similarly, the intervention group exhibited a 1-yr survival of 83.9% (CI, 80.6 to 87.2%) and a 2-yr survival of 69.3% (CI, 65.1 to 73.6%). An as-treated analysis revealed similar results (overall relative risk = 0.93; CI, 0.71 to 1.22; P = 0.6121). Mortality rates for the two groups remained similar even after adjustment for factors known to be associated with survival for patients undergoing PD (e.g., age, diabetes mellitus, serum albumin levels, normalized protein equivalent of total nitrogen appearance, and anuria). This study provides evidence that increases in peritoneal small-solute clearances within the range studied have a neutral effect on patient survival, even when the groups are stratified according to a variety of factors (age, diabetes mellitus, serum albumin levels, normalized protein equivalent of total nitrogen appearance, and anuria) known to affect survival. No clear survival advantage was obtained with increases in peritoneal small-solute clearances within the range achieved in this study.

Background: End-stage renal disease is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). In 1975, the US Renal Transplant Registry reported the first lupus patients, who received a renal transplant. This study reported 60% and 55% patient/graft survival respectively at a mean time of two years; these results were similar to those of non-lupus transplanted patients in this same post-transplant lapse time. Renal transplantation is a world wide accepted therapeutic option in the treatment of SLE patients., Patients and Methods: In order to identify the risk factors associated to renal graft loss in SLE patients and to compare graft survival between these patients and control transplant patients, matched by age, gender, haplotype match, and transplant date (+/- three years), we performed a retrospective analysis of all SLE patients that received a renal transplant in our Institute., Results: From 1967 to March 1997, 25 (5.5%) out of 452 renal transplants were performed in 22 SLE patients, mean age 29 +/- 10 years, 20 were female (90%). In 18 patients (85.7%) we obtained pre-transplant histological diagnosis: 13 (72%) type IV glomerulonephritis according to the OMS classification, three (17%) type VI, and two (11%) type III. Twelve patients (57%) were subjected to hemodialysis in the pre-transplant period and none (43%) to peritoneal dialysis. The time elapsed between the diagnosis of SLE and the start of dialysis was 50 +/- 70 months, the time on dialysis was 18 +/- 17 months, the post-transplant renal follow-up 46.9 +/- 41.5 months, and the graft source: 18 (78%) from living related (three sharing 0 haplotypes, 12 sharing 1 haplotype, and three sharing 2 haplotypes), and five (22%) from cadaver donors. Triple drug immunosuppresive therapy (cyclosporine, azathioprine, and prednisone) was employed in 17 patients and double drug therapy (azathioprine and prednisone) in the remaining six cases. We registered seven acute rejection episodes in five patients (30%), one of them lost the graft. Five patients presented a post-transplant thrombotic event, two of these were in the graft's artery. In two patients post-transplant SLE activity was documented, one case in with renal activity in the graft and the other with extrarenal activity. Risk factors analyzed for graft loss: number of pre-transplant thrombosis events, time elapsed between diagnosis of SLE at start of dialysis (< or = 6 months), time on dialysis (< or = 12 months), graft source, chronic rejection, and follow-up were not significant; in contrast, post-transplant thrombosis was the only identified risk factor for graft loss. Graft survival analysis at 50 months in SLE transplanted patients versus control non-SLE transplanted patients did not show significant differences (74% vs. 83%, log rank 0.11)., Conclusions: Post-transplant thrombosis was identified as a risk factor for graft loss. In concordance with recent studies, pre-transplant thrombosis, time elapsed between diagnosis of SLE at start of dialysis and time on dialysis were not risk factors for graft loss in this study. Graft survival in renal transplants recipients with SLE was not different from that of the general renal transplant population.