Relationship between volume status and blood pressure during chronic hemodialysis

Relationship between volume status and blood pressure during chronic hemodialysis.BackgroundThe relationship between volume status and blood pressure (BP) in chronic hemodialysis (HD) patients remains incompletely understood. Specifically, the effect of interdialytic fluid accumulation (or intradialytic fluid removal) on BP is controversial.MethodsWe determined the association of the intradialytic decrease in body weight (as an indicator of interdialytic fluid gain) and the intradialytic decrease in plasma volume (as an indicator of postdialysis volume status) with predialysis and postdialysis BP in a cross-sectional analysis of a subset of patients (N = 468) from the Hemodialysis (HEMO) Study. Fifty-five percent of patients were female, 62% were black, 43% were diabetic and 72% were prescribed antihypertensive medications. Dry weight was defined as the postdialysis body weight below which the patient developed symptomatic hypotension or muscle cramps in the absence of edema. The intradialytic decrease in plasma volume was calculated from predialysis and postdialysis total plasma protein concentrations and was expressed as a percentage of the plasma volume at the beginning of HD.ResultsPredialysis systolic and diastolic BP values were 153.1 ± 24.7 (mean ± SD) and 81.7 ± 14.8mm Hg, respectively; postdialysis systolic and diastolic BP values were 136.6 ± 22.7 and 73.9 ± 13.6mm Hg, respectively. As a result of HD, body weight was reduced by 3.1 ± 1.3kg and plasma volume was contracted by 10.1 ± 9.5%. Multiple linear regression analyses showed that eachkg reduction in body weight during HD was associated with a 2.95mm Hg (P = 0.004) and a 1.65mm Hg (P = NS) higher predialysis and postdialysis systolic BP, respectively. In contrast, each 5% greater contraction of plasma volume during HD was associated with a 1.50mm Hg (P = 0.026) and a 2.56mm Hg (P < 0.001) lower predialysis and postdialysis systolic BP, respectively. The effects of intradialytic decreases in body weight and plasma volume were greater on systolic BP than on diastolic BP.ConclusionsHD treatment generally reduces BP, and these reductions in BP are associated with intradialytic decreases in both body weight and plasma volume. The absolute predialysis and postdialysis BP levels are influenced differently by acute intradialytic decreases in body weight and acute intradialytic decreases in plasma volume; these parameters provide different information regarding volume status and may be dissociated from each other. Therefore, evaluation of volume status in chronic HD patients requires, at minimum, assessments of both interdialytic fluid accumulation (or the intradialytic decrease in body weight) and postdialysis volume overload

Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study

Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study. The safety of dietary protein and phosphorous restriction was evaluated in the Modification of Diet in Renal Disease (MDRD) Study. In Study A, 585 patients with a glomerular filtration rate (GFR) of 25 to 55 ml/min/1.73m2 were randomly assigned to a usual-protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/day). In Study B, 255 patients with a GFR of 13 to 24 ml/min/1.73m2 were randomly assigned to the low-protein diet or a very-low-protein diet (0.28 g/kg/day), supplemented with a ketoacid-amino acid mixture (0.28 g/kg/day). The low-protein and very-low-protein diets were also low in phosphorus. Mean duration of follow-up was 2.2 years in both studies. Protein and energy intakes were lower in the low-protein and very-low-protein diet groups than in the usual-protein group. Two patients in Study B reached a “stop point” for malnutrition. There was no difference between randomized groups in the rates of death, first hospitalizations, or other “stop points” in either study. Mean values for various indices of nutritional status remained within the normal range during follow-up in each diet group. However, there were small but significant changes from baseline in some nutritional indices, and differences between the randomized groups in some of these changes. In the low-protein and very-low-protein diet groups, serum albumin rose, while serum transferrin, body wt, percent body fat, arm muscle area and urine creatinine excretion declined. Combining patients in both diet groups in each study, a lower achieved protein intake (from food and supplement) was not correlated with a higher rate of death, hospitalization or stop points, or with a progressive decline in any of the indices of nutritional status after controlling for baseline nutritional status and follow-up energy intake. These analyses suggest that the low-protein and very-low-protein diets used in the MDRD Study are safe for periods of two to three years. Nonetheless, both protein and energy intake declined and there were small but significant declines in various indices of nutritional status. These declines are of concern because of the adverse effect of protein calorie malnutrition in patients with end-stage renal disease. Physicians who prescribe low-protein diets must carefully monitor patients' protein and energy intake and nutritional status

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/Vurea, a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome

Clinical trial of focal segmental glomerulosclerosis in children and young adults

This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled, 138 were randomized to cyclosporine (72) or to mycophenolate/dexamethasone (66). The primary analysis compared the levels of an ordinal variable measuring remission during the first year. The odds ratio (0.59) for achieving at least a partial remission with mycophenolate/dexamethasone compared to cyclosporine was not significant. Partial or complete remission was achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients at 12 months. The main secondary outcome, preservation of remission for 26 weeks following cessation of treatment, was not significantly different between these two therapies. During the entire 78 weeks of study, 8 patients treated with cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney failure. Thus, our study did not find a difference in rates of proteinuria remission following 12 months of cyclosporine compared to mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the small sample size might have prevented detection of a moderate treatment effect

Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life

Optimal therapy of patients with steroid-resistant primary focal segmental glomerulosclerosis (FSGS) remains controversial. This report describes the initial study design, baseline characteristics, and quality of life of patients enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2–40 years, with an estimated glomerular filtration rate >40 ml/min per 1.73 m2, a first morning urine protein-to-creatinine ratio over one, and resistant to corticosteroids were eligible. The primary outcome was complete or partial remission of proteinuria over 52 weeks after randomization. In all, 192 patients were screened, of whom 138 were randomized for treatment. Ethnic distributions were 53 black, 78 white, and 7 other. By self- or parent-proxy reporting, 26 of the 138 patients were identified as Hispanic. The baseline glomerular filtration rate was 112.4 (76.5, 180.0) ml/min per 1.73 m2, and urine protein was 4.0 (2.1, 5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than healthy controls and similar to that of patients with end-stage renal disease. Thus, the impact of FSGS on quality of life is significant and this measurement should be included in all trials

Strict blood pressure control associates with decreased mortality risk by APOL1 genotype.

Although APOL1 high-risk genotype partially accounts for the increased susceptibility of blacks to chronic kidney disease (CKD), whether APOL1 associates differentially with mortality risk remains controversial. Here we evaluate the association between APOL1 genotype and risk of death and determine whether APOL1 status modifies the association between strict versus usual blood pressure control and mortality risk. We performed a retrospective analysis of the African American Study of Kidney Disease and Hypertension trial that randomized black participants with CKD to strict versus usual blood pressure control from 1995 to 2001. This included 682 participants with known APOL1 genotype (157 with high-risk genotype) previously assigned to either strict (mean arterial pressure [MAP] 92 mm&nbsp;Hg or less) versus usual blood pressure control (MAP 102-107 mm&nbsp;Hg) during the trial. During a median follow-up of 14.5 years, risk of death did not differ between individuals with high- versus low-risk APOL1 genotypes (unadjusted hazard ratio 1.00 [95% confidence interval 0.76-1.33]). However, a significant interaction was detected between the APOL1 risk group and blood pressure control strategy. In the APOL1 high-risk group, the risk of death was 42% lower comparing strict versus usual blood pressure control (0.58 [0.35-0.97]). In the APOL1 low-risk group, the risk of death comparing strict versus usual blood pressure control was not significantly different (1.09 [0.84-1.43]). Thus, strict blood pressure control during CKD associates with a lower risk of death in blacks with the high-risk CKD APOL1 genotype. Knowledge of APOL1 status could inform selection of blood pressure treatment targets in black CKD patients

Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis.

RATIONALE & OBJECTIVE: Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate if reductions in proteinuria following treatment are associated with greater kidney survival. STUDY DESIGN: Cohort analysis of clinical trial participants SETTING & PARTICIPANTS: Patients with steroid resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine to mycophenolate mofetil plus dexamethasone. PREDICTORS: Reduction in proteinuria measured during 26 weeks after initiating treatment OUTCOMES: Repeated measures of estimated glomerular filtration rate (eGFR) and, time to end-stage kidney disease (ESKD) or death assessed between 26 weeks and 54 months after randomization ANALYTIC APPROACH: Multivariable, linear-mixed effects models with subject-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable, time-varying Cox-proportional hazards models were used to estimate the association of changes in proteinuria with time to ESKD or death. RESULTS: 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1 unit reduction in log-transformed urinary protein:creatinine ratio was associated with a 3.90 ml/year rise in eGFR (95% CI=2.01 to 5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to end-stage kidney disease: the HR for ESKD or death per 1 unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI=0.12 to 0.44). LIMITATIONS: Limited to individuals with steroid-resistant FSGS followed for a maximum of five-years. CONCLUSIONS: These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials