Characterization of Mesoamerican Nephropathy in a Kidney Failure Hotspot in Nicaragua.

BACKGROUND: Mesoamerican nephropathy (MeN) is a kidney disease of unknown cause that mainly affects working-age men in Central America. Despite being a major cause of morbidity and mortality in this region, its clinical characteristics have not been well defined. STUDY DESIGN: Cross-sectional family-based study. SETTING & PARTICIPANTS: 266 members of 24 families with high chronic kidney disease (CKD) burdens in a MeN hotspot in Northwestern Nicaragua. We compared clinical and biochemical characteristics of affected individuals first with their unaffected relatives and then with NHANES (National Health and Nutrition Examination Survey) participants with CKD in order to reveal identifying features of MeN. PREDICTOR: CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women. OUTCOMES: Clinical and biochemical parameters, including serum sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, and uric acid. RESULTS: Hyperuricemia, in many cases severe, was common among patients with MeN. Uric acid levels in patients with MeN were higher than those in NHANES participants (mean, 9.6 vs 7.4mg/dL for men in each group) despite more frequent use of uric acid-lowering medications in Nicaraguan individuals (71.7% vs 11.2%). In multivariable linear mixed-effects regression analysis, uric acid levels were 2.0mg/dL (95% CI, 1.0-3.0; P<0.001) higher in patients with MeN compared with their NHANES counterparts after adjusting for age, estimated glomerular filtration rate, and uric acid-lowering therapies. In contrast to prior reports, hyponatremia and hypokalemia were not common. LIMITATIONS: CKD defined by single serum creatinine measurement; population likely not representative of full MeN phenotype spectrum across Central America; major differences between MeN and NHANES groups in important characteristics such as age, ancestry, and recruitment method. CONCLUSIONS: Hyperuricemia out of proportion to the degree of decreased kidney function was common among Nicaraguan patients with MeN. Our results suggest that rather than being solely a consequence of CKD, hyperuricemia may play a role in MeN pathogenesis, a hypothesis that deserves further study.

Sodium modelling to reduce intradialytic hypotension during haemodialysis for acute kidney injury in the intensive care unit.

AIM: Intradialytic hypotension often complicates haemodialysis for patients with acute kidney injury (AKI) and may impact renal recovery. Sodium modelling is sometimes used as prophylaxis against intradialytic hypotension in the chronic haemodialysis population, but there is little evidence for its use among critically ill patients with AKI. METHODS: A retrospective cohort with AKI requiring intermittent haemodialysis in the intensive care unit from 2001 to 2008 was used to study the association of prophylactic sodium modelling and multiple outcomes. Outcomes included a composite of in-hospital death or dialysis dependence at hospital discharge, as well as intradialytic hypotension, ultrafiltration goal achievement and net ultrafiltration volume. Associations were estimated using logistic regression, mixed linear models and generalized estimating equations adjusting for demographic and clinical characteristics. RESULTS: One hundred and ninety-one individuals who underwent 892 sessions were identified; sodium modelling was prescribed in 27.1% of the sessions. In adjusted analyses, sodium modelling was not significantly associated with intradialytic hypotension (P = 0.67) or with the ultrafiltration goal achievement (P = 0.06). Sodium modelling during the first dialysis session was numerically associated with lower risk for the composite of in-hospital death or dialysis dependence: adjusted odds ratio (95% confidence interval) 0.39 (0.15-1.02; P = 0.06); however, this association did not reach statistical significance. CONCLUSION: We did not observe statistically significant associations between sodium modelling and improved outcomes among AKI patients receiving intermittent dialysis in the intensive care unit. However, suggestive findings warrant further study.

Association of mortality risk with various definitions of intradialytic hypotension.

Intradialytic hypotension is a serious and frequent complication of hemodialysis; however, there is no evidence-based consensus definition of intradialytic hypotension. As a result, coherent evaluation of the effects of intradialytic hypotension is difficult. We analyzed data from 1409 patients in the HEMO Study and 10,392 patients from a single large dialysis organization to investigate the associations of commonly used intradialytic hypotension definitions and mortality. Intradialytic hypotension definitions were selected a priori on the basis of literature review. For each definition, patients were characterized as having intradialytic hypotension if they met the corresponding definition in at least 30% of baseline exposure period treatments or characterized as control otherwise. Overall and within subgroups of patients with predialysis systolic BP<120 or 120-159 mmHg, an absolute nadir systolic BP<90 mmHg was most potently associated with mortality. Within the subgroup of patients with predialysis BP≥160 mmHg, nadir BP<100 mmHg was most potently associated with mortality. Intradialytic hypotension definitions that considered symptoms, interventions, and decreases in BP during dialysis were not associated with outcome, and when added to nadir BP, symptom and intervention criteria did not accentuate associations with mortality. Our results suggest that nadir-based definitions best capture the association between intradialytic hypotension and mortality.

Updates on the management of diabetes in dialysis patients.

Diabetes mellitus is the leading cause of end-stage renal disease (ESRD) in the U.S. and many countries globally. The role of improved glycemic control in ameliorating the exceedingly high mortality risk of diabetic dialysis patients is unclear. The treatment of diabetes in ESRD patients is challenging, given changes in glucose homeostasis, the unclear accuracy of glycemic control metrics, and the altered pharmacokinetics of glucose-lowering drugs by kidney dysfunction, the uremic milieu, and dialysis therapy. Up to one-third of diabetic dialysis patients may experience spontaneous resolution of hyperglycemia with hemoglobin A1c (HbA1c) levels <6%, a phenomenon known as "Burnt-Out Diabetes," which remains with unclear biologic plausibility and undetermined clinical implications. Conventional methods of glycemic control assessment are confounded by the laboratory abnormalities and comorbidities associated with ESRD. Similar to more recent approaches in the general population, there is concern that glucose normalization may be harmful in ESRD patients. There is uncertainty surrounding the optimal glycemic target in this population, although recent epidemiologic data suggest that HbA1c ranges of 6% to 8%, as well as 7% to 9%, are associated with increased survival rates among diabetic dialysis patients. Lastly, many glucose-lowering drugs and their active metabolites are renally metabolized and excreted, and hence, require dose adjustment or avoidance in dialysis patients.

Altered taste perception and nutritional status among hemodialysis patients.

OBJECTIVE: The objective of this study was to examine the association between altered taste perception and nutritional status among hemodialysis patients. DESIGN: We performed a post hoc analysis of data from the Hemodialysis study (n = 1,745). Taste perception was assessed at baseline and then updated annually using an item from a quality of life survey that asked "During the past 4 weeks, to what extent were you bothered by loss of taste?" Responses were categorized as normal taste perception if subjects answered "not at all" or altered taste perception if they reported any degree of bother. Time-updated logistic regression models were used to evaluate predictors of altered taste perception. Time-updated linear regression models were used to examine the association between altered taste perception and indices of nutritional status. Multivariable proportional hazards and Poisson models were used to assess association between altered taste perception and mortality and hospitalization, respectively. RESULTS: At baseline, 34.6% reported altered taste perception, which was associated with poorer baseline nutritional status. On time-updated analysis, altered taste perception was associated with a persistently higher proportion of subjects requiring enteral nutritional supplements and lower serum albumin, serum creatinine, normalized protein catabolic rate, protein intake, sodium intake, and mid-arm muscle circumference. Altered taste perception at baseline was independently associated with increased all-cause mortality: adjusted hazard ratio (95% confidence interval) of 1.17 (1.01-1.37), although not with increased rate of hospitalization. CONCLUSION: Altered taste perception was common among prevalent hemodialysis patients and was independently associated with poorer indices of nutritional status and increased all-cause mortality.

Effects of L-carnitine on dialysis-related hypotension and muscle cramps: a meta-analysis.

BACKGROUND: L-Carnitine is an endogenous compound thought to be helpful in treating patients with dialysis-related hypotension and muscle cramps; however, sufficient evidence for these indications is lacking. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adult patients with end-stage renal disease receiving long-term hemodialysis. SELECTION CRITERIA FOR STUDIES: All published English-language reports of randomized placebo-controlled trials of L-carnitine supplementation in adult long-term hemodialysis patients. INTERVENTION: Supplemental L-carnitine (or placebo) for at least 8 weeks. OUTCOME: Random-effects pooled odds ratio for intradialytic cramping or hypotension in L-carnitine-treated participants. RESULTS: Of 317 potentially relevant articles, 7 (total enrollment of 193 patients) met criteria for inclusion. Four articles reported results for both hypotension and cramps, 1 had results for only hypotension, and 2 reported results for only cramps. Using data from all 6 relevant trials, the pooled odds ratio for cramping after L-carnitine supplementation was 0.30 (95% confidence interval, 0.09 to 1.00; P = 0.05). Analysis of the 5 studies examining the response of intradialytic hypotension to l-carnitine supplementation yielded a pooled odds ratio of 0.28 (95% confidence interval, 0.04 to 2.23; P = 0.2). LIMITATIONS: The small number of available studies yielded limited statistical power. In addition, there was considerable interstudy heterogeneity. CONCLUSIONS: Although suggestive in the case of muscle cramping, the available evidence does not confirm a beneficial effect of L-carnitine supplementation on dialysis-related muscle cramping or intradialytic hypotension. Additional study in the form of large rigorous randomized trials is needed in both cases.

Association between long-term blood pressure variability and mortality among incident hemodialysis patients.

BACKGROUND: Blood pressure variability (BPV) is one putative risk factor for cardiovascular disease and mortality in hemodialysis patients. The purposes of this study are to identify a suitable metric of long-term BPV in this population and determine whether an association between BPV and all-cause mortality exists. STUDY DESIGN: Retrospective cohort study. SETTINGS & PARTICIPANTS: Patients from the Accelerated Mortality on Renal Replacement (ArMORR) cohort who were adult, incident to hemodialysis at any Fresenius Medical Care unit between June 2004 and August 2005, and had suitable blood pressure data were studied (n = 6,961). PREDICTOR: Predialysis blood pressures measured between dialysis days 91 and 180 were used to determine each patient's absolute level of, trend in (slope over time), and variability in blood pressure. OUTCOME: All-cause mortality beginning immediately after day 180 and continuing through day 365 or until censoring (median follow-up, 185 days). RESULTS: Of the 4 candidate BPV metrics, only average residual-intercept ratio adequately distinguished BPV from absolute blood pressure level and temporal blood pressure trend. In the primary analysis, each SD increase in systolic and diastolic BPV was associated with adjusted hazard ratios for all-cause mortality of 1.13 (95% confidence interval, 1.03 to 1.23) and 1.15 (95% confidence interval, 1.06 to 1.26), respectively. Results were consistent across multiple sensitivity analyses in which inclusion and exclusion criteria and timing of blood pressure measurements were varied. LIMITATIONS: Contingency of results on the validity of mathematic description of BPV; potential for misclassification bias and residual confounding. CONCLUSIONS: Provided the mathematical descriptions of BPV are valid, the data suggest that systolic and diastolic BPV is associated with all-cause mortality in incident hemodialysis patients. Additional study is necessary to confirm and generalize findings, assess the interplay between systolic and diastolic BPV, and assess causality.

Prescribed dietary phosphate restriction and survival among hemodialysis patients.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia is common among hemodialysis patients. Although prescribed dietary phosphate restriction is a recommended therapy, little is known about the long-term effects on survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a post hoc analysis of data from the Hemodialysis Study (n = 1751). Prescribed dietary phosphate was recorded at baseline and annually thereafter. Marginal structural proportional hazard models were fit to estimate the adjusted association between dietary phosphate restriction and mortality in the setting of time-dependent confounding. RESULTS: At baseline, prescribed daily phosphate was restricted to levels ≤ 870, 871 to 999, 1000, 1001 to 2000 mg, and not restricted in 300, 314, 307, 297, and 533 participants, respectively. More restrictive prescribed dietary phosphate was associated with poorer indices of nutritional status on baseline analyses and a persistently greater need for nutritional supplementation but not longitudinal changes in caloric or protein intake. On marginal structural analysis, there was a stepwise trend toward greater survival with more liberal phosphate prescription, which reached statistical significance among subjects prescribed 1001 to 2000 mg/d and those with no specified phosphate restriction: hazard ratios (95% CIs) 0.73 (0.54 to 0.97) and 0.71 (0.55 to 0.92), respectively. Subgroup analysis suggested a more pronounced survival benefit of liberal dietary phosphate prescription among nonblacks, participants without hyperphosphatemia, and those not receiving activated vitamin D. CONCLUSIONS: Prescribed dietary phosphate restriction is not associated with improved survival among prevalent hemodialysis patients, and increased level of restriction may be associated with greater mortality particularly in some subgroups.

Association of hemoglobin variability and mortality among contemporary incident hemodialysis patients.

BACKGROUND AND OBJECTIVES: Evidence exists that variability in hemoglobin may be an independent risk factor for mortality among hemodialysis patients. These observations were based on a 1996 cohort, a time when anemia management differed greatly from present. Design, settings, participants and measurements: A retrospective cohort study of patients incident to Fresenius Medical Care units between 2004 and 2005 (n = 6644). Hemoglobin variability (Hgb-Var) was defined for each subject as the residual SD of a linear regression model of time on hemoglobin. RESULTS: The mean (SD) of Hgb-Var was 1.13 (0.55) g/dl. In the primary analysis, each g/dl increase of Hgb-Var was associated with an adjusted hazard ratio (95% confidence interval) for all-cause mortality of 1.11 (0.92 to 1.33). No significant interaction with Hgb-Var and mortality was found on the basis of age (P = 0.22), arterial disease (P = 0.45), Hgb slope (P = 0.68), or mean Hgb (P = 0.78). When Hgb-Var was defined by a regression model that included a quadratic term for time (enabling descriptions of curvilinear hemoglobin trajectories), model fit was greatly improved (P for difference <0.001). The corresponding adjusted hazard ratio (95% confidence interval) for all-cause mortality was 1.17 (0.93 to 1.49). CONCLUSIONS: Hgb-Var was not found to be associated with all-cause mortality when examined in a contemporary incident hemodialysis population. More research is needed to determine whether differences in these findings compared with prior analyses relate to temporal trends in anemia management or from differences in the relationship between Hgb-Var and outcomes among incident versus prevalent hemodialysis patients.