Obesity and Outcomes in ESRD Patients Receiving Peritoneal Dialysis

In developed countries, since the mid-1980s the prevalence of obesity among patients with end-stage renal disease (ESRD) has increased. The increase parallels that in the general population; however, the trends in the ESRD population in the United States have been more dramatic. The difference in the trends may be explained by the increased risk for chronic kidney disease in patients who are obese and those with diabetes, as well as by the “obesity paradox” of patients with ESRD, in whom there is an association between obesity and improved survival.

The obesity paradox has been seen in patients with ESRD who receive hemodialysis; data are inconsistent in patients on peritoneal dialysis. However, according to Yoshitsugu Obi, PhD, and colleagues, the data relating to peritoneal dialysis were derived from noncontemporary cohorts, limiting the generalizability to the present-day patient populations. Due to advances in delivery of peritoneal dialysis, as well as efficacy and safety, mortality in the peritoneal dialysis population has decreased more rapidly than in the hemodialysis population.

Dr. Obi et al. recently conducted a historical cohort study to test the hypothesis that there is an incremental association between the severity of obesity, expressed as body mass index (BMI), and adverse clinical outcomes and that the survival advantage of peritoneal dialysis is attenuated in patients with ESRD who are obese. Results of the study were reported in the American Journal of Kidney Diseases [2018;71(6):802-813).

In total, 15,573 incident peritoneal dialysis patients ≥18 years of age from a large dialysis organization in the United States from January 1, 2007, through December 31, 2011, were included in the study. BMI was categorized in six groups: <20, 20 to <25, 25 to <30, 30 to <35, 35 to <40, and ≤40 kg/m2. Severe obesity was defined as BMI ≥35 kg/m2.

Overall, mean age of the study cohort was 56 years, 56% were male, 58% were non-Hispanic white, 22% were non-Hispanic black, and 62% had diabetes. Median BMI was 28 kg/m2, and prevalences of BMI categories (kg/m2) were <20, 5.5%; 20 to <25, 26%; 25 to <30, 32%; 30 to <35, 21%; 35 to <40, 10%; and ≥40, 5.5%. Patients with higher BMI had greater renal creatinine clearance (CLcr) and lower peritoneal CLcr. Across higher BMI categories, there was a significant trend toward greater total CLcr.  There was no difference in renal Kt/V across the BMI categories; however, patients with higher BMI showed lower peritoneal Kt/V, resulting in lower total Kt/V.

Of the original peritoneal dialysis cohort,  2568 patients transferred to hemodialysis therapy during follow-up.  A total of 1863 patients died, and 1271 underwent kidney transplantation during follow-up, including 90 days after transferring to hemodialysis therapy. There was a significant association between higher BMI and shorter time to transfer to hemodialysis therapy (P for trend <.001) and longer time to kidney transplantation (P for trend <.001). The association between higher BMI  and more frequent peritonitis-related hospitalization was of borderline significance ( P for trend=.05).

There was a U-shaped association between BMI and all-cause mortality. In the case-risk adjusted model, patients with BMI 30 to <35 kg/m2 had the greatest survival. The mortality risk of the lowest of the six BMI categories was incrementally attenuated with sequential adjustments. There was also attenuation in lower mortality risk associated with BMI categories ≥25 kg/m2 and even reversal in BMI categories ≥35 kg/m2 following adjustment for laboratory variables. Associations between higher BMI and lower likelihood of undergoing kidney transplantation were consistent across all BMI categories, particularly in BMI categories >30 kg/m2 (P for trend <.001).

There were 2311 hospitalizations related to peritonitis among 1315 patients, and 32,723 non–peritonitis-related hospitalizations among 9442 patients. In all adjustment models, there was a trend toward higher incidence of peritonitis-related hospitalizations across higher categories of BMI (P for trend in the fully adjusted model .001). There was an association between higher BMI and lower incidence of non–peritonitis-related hospitalizations in the case-mix adjusted model (P for trend <.001); the association was not significant in the unadjusted and fully adjusted models.

In comparisons of changes in solute clearance indexes across the six BMI categories, obese patients initiated peritoneal dialysis therapy at higher renal CLcr levels but had faster declines in renal CLcr (P for trend <.001). At baseline, renal Kt/V was comparable across BMI categories, but declined faster among obese patients (P for trend <.001). Compared with lean patients, obese patients had lower peritoneal Kt/V at baseline and greater increases in Kt/V (P for trend<.001).

Ninety percent of peritoneal patients (n=14,007) were matched in a 1:2 ratio to 28,014 hemodialysis patients based on BMI, age, sex, race/ethnicity, ESRD reason, dialysis vintage, the three BMI categories used for this analysis (<25, 25-<35, and ≥35 kg/m2), and Charlson Comorbidity Index score. Compared with matched hemodialysis patients, mortality was lower among peritoneal dialysis patients in the BMI categories <25 and 25-<35 kg/m2; survival was equivalent in BMI category ≥35 kg/m2 (P for interaction=.001 [vs <25 kg/m2]). The attenuation in survival differences among patients with severe obesity was seen in patients with diabetes; it was not seen in patients without diabetes.

The researchers acknowledged several limitations to the study, including the observational design that may have led to residual confounding and unmeasured confounders, the possibility of selection bias because residual kidney clearance was not consistently measured in all patients, and lack of data on post-kidney transplantation outcomes.

The researchers concluded by saying, “Obesity is associated with various adverse outcomes among peritoneal dialysis patients but should not be considered an absolute contraindication to peritoneal dialysis given the equivalent mortality of obese peritoneal dialysis versus hemodialysis patients observed in our study. These findings make it imperative to implement interventions and strategies that would safely prolong time on peritoneal dialysis therapy among obese patients, such as larger dwell volumes, frequent evaluation of residual kidney function with proper adjustment of peritoneal dialysis prescription, and prevention of peritonitis and residual kidney function decline. Further studies are also needed to test whether successful weight reduction reduces peritoneal dialysis-related adverse events and enhances the survival advantage of peritoneal dialysis among obese patients.”

Takeaway Points

  1. There are few current data on the association between obesity and clinical outcomes among patients with end-stage renal disease on peritoneal dialysis.
  2. In a retrospective cohort study among 15,573 incident peritoneal dialysis patients in a large US dialysis organization (2007-2011), there was an association between higher body mass index (BMI) and shorter time to transfer to hemodialysis therapy, longer time to kidney transplantation, and more frequent peritonitis-related hospitalizations.
  3. Compared with matched hemodialysis patients, patients on peritoneal dialysis had lower mortality in BMI <25 and 25 to <35 kg/m2; survival was equivalent in patients with BMI ≥35 kg/m2.