Summary Background Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional ...differences in acute kidney injury recognition, management, and outcomes. Methods In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person. Findings Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p=0.33; p<0.0001 for all other comparisons). Hypotension (1615 40% patients) and dehydration (1536 38% patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 46% of 1153 vs 518 32% of 1605 in UMICs vs 492 39% of 1260 in HICs) and hypotension in HICs (564 45% of 1260 vs 611 38%% of 1605 in UMICs vs 440 38% of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 12% of 1076) than in HICs (125 10% of 1230) and UMICs (169 11% of 1549). Interpretation We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community health-care settings, especially in LICs. Funding International Society of Nephrology.
Background High interdialytic weight gain (IDWG) is associated with adverse outcomes in hemodialysis (HD) patients. We identified temporal and regional trends in IDWG, predictors of IDWG, and ...associations of IDWG with clinical outcomes. Study Design Analysis 1: sequential cross-sections to identify facility- and patient-level predictors of IDWG and their temporal trends. Analysis 2: prospective cohort study to assess associations between IDWG and mortality and hospitalization risk. Setting & Participants 21,919 participants on HD therapy for 1 year or longer in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 2 to 5 (2002-2014). Predictors Analysis 1: study phase, patient demographics and comorbid conditions, HD facility practices. Analysis 2: relative IDWG, expressed as percentage of post-HD weight (<0%, 0%-0.99%, 1%-2.49%, 2.5%-3.99% reference, 4%-5.69%, and ≥5.7%). Outcomes Analysis 1: relative IDWG as a continuous variable using linear mixed models; analysis 2: mortality; all-cause and cause-specific hospitalization using Cox regression, adjusting for potential confounders. Results From phase 2 to 5, IDWG declined in the United States (−0.29 kg; −0.5% of post-HD weight), Canada (−0.25 kg; −0.8%), and Europe (−0.22 kg; −0.5%), with more modest declines in Japan and Australia/New Zealand. Among modifiable factors associated with IDWG, the most notable was facility mean dialysate sodium concentration: every 1-mEq/L greater dialysate sodium concentration was associated with 0.13 (95% CI, 0.11-0.16) greater relative IDWG. Compared to relative IDWG of 2.5% to 3.99%, there was elevated risk for mortality with relative IDWG ≥ 5.7% (adjusted HR, 1.23; 95% CI, 1.08-1.40) and elevated risk for fluid-overload hospitalization with relative IDWG ≥ 4% (HRs of 1.28 95% CI, 1.09-1.49 and 1.64 95% CI, 1.27-2.13 for relative IDWGs of 4%-5.69% and ≥5.7%, respectively). Limitations Possible residual confounding. No dietary salt intake data. Conclusions Reductions in IDWG during the past decade were partially explained by reductions in dialysate sodium concentration. Focusing quality improvement strategies on reducing occurrences of high IDWG may improve outcomes in HD patients.
The Frequent Hemodialysis Network Daily Trial randomized 245 patients to receive six (frequent) or three (conventional) in-center hemodialysis sessions per week for 12 months. As reported previously, ...frequent in-center hemodialysis yielded favorable effects on the coprimary composite outcomes of death or change in left ventricular mass and death or change in self-reported physical health. Here, we determined the long-term effects of the 12-month frequent in-center hemodialysis intervention. We determined the vital status of patients over a median of 3.6 years (10%-90% range, 1.5-5.3 years) after randomization. Using an intention to treat analysis, we compared the mortality hazard in randomized groups. In a subset of patients from both groups, we reassessed left ventricular mass and self-reported physical health a year or more after completion of the intervention; 20 of 125 patients (16%) randomized to frequent hemodialysis died during the combined trial and post-trial observation periods in contrast to 34 of 120 patients (28%) randomized to conventional hemodialysis. The relative mortality hazard for frequent versus conventional hemodialysis was 0.54 (95% confidence interval, 0.31 to 0.93); with censoring of time after kidney transplantation, the relative hazard was 0.56 (95% confidence interval, 0.32 to 0.99). Bayesian analysis suggested a relatively high probability of clinically significant benefit and a very low probability of harm with frequent hemodialysis. In conclusion, a 12-month frequent in-center hemodialysis intervention significantly reduced long-term mortality, suggesting that frequent hemodialysis may benefit selected patients with ESRD.
Background Current evidence does not clearly identify the contribution of kidney function decline and mortality to racial disparities in end-stage renal disease (ESRD) incidence. We used observed ...estimated glomerular filtration rate (eGFR) to project the time of onset of kidney failure and examined mortality to better understand these racial disparities. Study Design Retrospective cohort. Setting & Participants Adult members of Kaiser Permanente Southern California in 2003-2009 with more than 2 serum creatinine tests and more than 180 days between tests: 526,498 whites, 350,919 Hispanics, 136,923 blacks, and 105,476 Asians. Predictor Race/ethnicity. Outcomes ESRD (dialysis or transplantation); mortality. Measurements eGFR decline was modeled using linear regression. Kidney failure was projected based on predicted eGFR <15 mL/min/1.73 m2 at specified times. Racial differences in projected kidney failure and mortality in those with projected kidney failure were estimated with adjustment for age, sex, and entry eGFR. Results Blacks had more extreme rates of eGFR decline (1st percentile, −23.6 mL/min/1.73 m2 per year), followed by Hispanics (−20.9 mL/min/1.73 m2 per year), whites (−20.1 mL/min/1.73 m2 per year), and Asians (−17.6 mL/min/1.73 m2 per year; P < 0.001). There were 25,065 whites, 11,368 Hispanics, 6,785 blacks, and 3,176 Asians with projected kidney failure during the study period. The ORs for projected kidney failure versus whites during CKD stages 3 and 4 were 1.54 (95% CI, 1.46-1.62) in blacks, 1.49 (95% CI, 1.42-1.56) in Hispanics, and 1.41 (95% CI, 1.32-1.51) in Asians. For those with projected kidney failure, the HRs of death versus whites during CKD stages 3 and 4 were 0.82 (95% CI, 0.77-0.88) in blacks, 0.67 (95% CI, 0.63-0.72) in Hispanics, and 0.58 (95% CI, 0.52-0.65) in Asians. Limitations Results may not generalize to the uninsured or subgroups within a race. Projected kidney failure was based on linear trends from clinically obtained eGFR. Conclusions We found more extreme rates of eGFR decline in blacks. Projected kidney failure during CKD stages 3 and 4 was high in blacks, Hispanics, and Asians relative to whites. Mortality for those with projected kidney failure was highest in whites. Differences in eGFR decline and mortality contributed to racial disparities in ESRD incidence.
Patients with chronic kidney disease (CKD) are often volume expanded and hypertensive. Few controlled studies have assessed the effects of a sodium-restricted diet (SRD) in CKD.
We conducted a ...randomized crossover trial to evaluate the effect of SRD (target <2 g sodium per day) versus usual diet on hydration status (by bioelectrical impedance spectroscopy) and blood pressure (BP) between May of 2009 and May of 2013. A total of 58 adults with stage 3-4 CKD were enrolled from two academic sites: University of Michigan (
=37) and University of North Carolina at Chapel Hill (
=21); 60% were men, 43% were diabetic, 93% were hypertensive, and mean age was 61 years. Participants followed SRD or usual diet for 4 weeks, followed by a 2-week washout period and a 4-week crossover phase. During the SRD, dieticians provided counseling every 2 weeks, using motivational interviewing techniques.
Whole-body extracellular volume and calf intracellular volume decreased by 1.02 L (95% confidence interval 95% CI, -1.48 to -0.56;
<0.001) and -0.06 L (95% CI, -0.12 to -0.01;
=0.02), respectively, implying decreased fluid content on the SRD compared with usual diet. Significant reductions in urinary sodium (-57.3 mEq/24 h; 95% CI, -81.8 to -32.9), weight (-2.3 kg; 95% CI, -3.2 to -1.5), and 24-hour systolic BP (-10.8 mmHg; 95% CI, -17.0 to -4.6) were also observed (all
<0.01). Albumin-to-creatinine ratio did not change significantly and mean serum creatinine increased slightly (0.1 mg/dl; 95% CI, -0.01 to 0.2;
=0.06). No period or carryover effects were observed. Results were similar when analyzed from phase 1 only before crossover, although
values were modestly larger because of the loss of power.
In this randomized crossover trial, implementation of SRD in patients with CKD stage 3-4 resulted in clinically and statistically significant improvement in BP and hydration status. This simple dietary intervention merits a larger trial in CKD to evaluate effects on major clinical outcomes.
Bioimpedance analysis (BIA) is accepted for the assessment of total-body water (TBW), intracellular fluid (ICF) and extracellular fluid (ECF). We aimed to compare precision and accuracy of single and ...multi-frequency-BIA to direct estimation methods (DEMs) of TBW, ECF, and ICF in hemodialysis patients. Linear regression analysis of volume estimates in 49 patients by single- and multi-frequency-BIA correlated significantly with DEMs. Bland-Altman analysis (BAA) found systemic bias for ECF single-frequency-BIA vs. ECF-DEMs. No other systematic biases were found. Proportional errors were found by BAA of ICF and ECF assessments with single- and multi-frequency bioimpedance spectroscopy compared to the DEMs. Comparisons of indirect methods (IEMs) to DEMs showed no significant differences and proportional errors. Root mean-squared-error analysis suggested slightly better accuracy and precision of ICF single-frequency-BIA vs. DEMs over ICF multi-frequency-BIA and IEMs to DEMs, and slightly better performance for ECF multi-frequency-BIA over both respective other methods. Compared to DEMs, there is slightly better accuracy for ECF multi- over single-frequency-BIA and ICF single- over multi-frequency-BIA. However the margin of differences between direct and indirect methods suggests that none of the analyzed methods served as a true “gold standard”, because indirect methods are almost equally precise compared to DEMs.
Drinking water contaminated by pathogenic micro-organisms increases the risk of infectious gastrointestinal disease which could potentially lead to acute kidney injury and even death, particularly ...amongst the young and the elderly. Earlier studies have shown a substantial reduction in the incidence of diarrheal disease over a period of one year using a polysulfone membrane water gravity-powered water filtration device. The current report is a continuation of these studies to assess the long-term effects of the innovative method on diarrheal incidence rates over a 4-year follow-up period. This follow-up study monitored the trend of self-reported diarrheal events in all households in the previously studied villages for 5 months, in the last half of each study year, using the same questionnaire utilized in the earlier study. Three villages that had no device yet installed served as controls. We computed monthly diarrheal incidence rates for all study years (standardized to per 100 person-months) and compared these to the pre-device incidence rate in 2018 and in the control group, using the Wilcoxon rank sum exact test. The average diarrheal incidence rates of 1.5 p100pm in 2019, 2.19 p100pm in 2021, and 0.54p100pm in 2022 were significantly different from an earlier study that reported 17.8 p100pm rates before the devices were installed in 2018, (all p-values < 0.05). Concomitantly, self-reported diarrheal infections were substantially higher in the "control villages" not yet having the filtration device installed (80.9, 77.6, and 21.5 per 100 pm). The consistent and large reduction in diarrhea incidence documents the long-term efficacy of the use of the membrane filtration device. This simple water purification method using gravity flow improves public health in remote regions with limited resources.
In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical ...health, and other intermediate outcomes among patients undergoing maintenance hemodialysis.
Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Secondary outcomes included cognitive performance; self-reported depression; laboratory markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates of hospitalization and of interventions related to vascular access.
Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/V(urea) (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54±0.56 vs. 2.49±0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval CI, 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents.
Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT00264758.).
Heart rate variability (HRV), a noninvasive measure of autonomic dysfunction and a risk factor for cardiovascular disease (CVD), has not been systematically studied in nondialysis chronic kidney ...disease (CKD).
HRV was assessed using 24-h Holter monitoring in 305 subjects from the Renal Research Institute-CKD Study, a four-center prospective cohort of CKD (Stages 3-5). Multiple linear regression was used to assess predictors of HRV (both time and frequency domain) and Cox regression used to predict outcomes of CVD, composite of CVD/death and end-stage renal disease (ESRD).
A total of 47 CVD, 67 ESRD and 24 death events occurred over a median follow-up of 2.7 years. Lower HRV was significantly associated with older age, female gender, diabetes, higher heart rate, C-reactive protein and phosphorus, lower serum albumin and Stage 5 CKD. Lower HRV (mostly frequency domain) was significantly associated with higher risk of CVD and the composite end point of CVD or death. Significantly, lower HRV (frequency domain) was associated with higher risk of progression to ESRD, although this effect was relatively weaker.
This study draws attention to the importance of HRV as a relatively under recognized predictor of adverse cardiovascular and renal outcomes in patients with nondialysis CKD. Whether interventions that improve HRV will improve these outcomes in this high-risk population deserves further study.
In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude ...and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 0.62-0.90). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.
PDF
