Renal anemia and hyporesponsiveness to ESA for preservation of residual kidney function in patients undergoing peritoneal dialysis

Abstract

Preservation of residual kidney function (RKF) is important in patients undergoing peritoneal dialysis (PD). We aimed to examine the association between anemia management and residual urine output using data from a nationwide survey of dialysis patients. After excluding patients with anuria at baseline from the Total cohort of 2,712, 659 of 1,640 patients developed anuria during a median follow-up of 2.5 (interquartile range: 1.5-4.2) years. Urine volume decreased more rapidly as hemoglobin decreased or as the erythropoiesis-stimulating agent (ESA) resistance index (ERI) increased. The hazard ratios with 95% confidence intervals for the development of anuria, defined as residual urine volume ≤ 100 mL/day, were 1.65 (1.20-2.27), 1.39 (1.08-1.77), and 1.32 (1.07-1.63) for hemoglobin levels of < 9.0, 9.0-9.9, and 10.0-10.9 g/dL compared with 11.0-11.9 g/dL, and 1.35 (1.10-1.66) and 1.41 (1.14-1.73) for the second and third tertiles of ERI compared with the first tertile. In conclusion, patients with a low hemoglobin level or a high ERI were more likely to experience a decline in residual urine output and to develop anuria. Further studies are needed to investigate the effects of interventions that could improve renal anemia and/or ESA hyporesponsiveness on RKF preservation.

Keywords: Anuria; Erythropoiesis-stimulating agent resistance index; Hyporesponsiveness to erythropoiesis-stimulating agent; Peritoneal dialysis; Residual kidney function.

Fig. 1

Flow diagram of patient selection. In the Total cohort, patients undergoing PD with available data on ESA dose and residual urine were included to examine the association between urine output and ERI. In the Analytic cohort, after excluding those with a urine volume ≤ 100 mL/day at baseline and those with only one urine data available, we examined the longitudinal association of ERI with urine output. PD, peritoneal dialysis; ESA, erythropoiesis-stimulating agent; ERI, ESA resistance index; UV, urine volume.

Fig. 2

Longitudinal trajectories of residual urine output across levels of hemoglobin and ESA resistance index at baseline. Longitudinal trajectories of residual urine output across levels of hemoglobin (A) and ERI tertiles (B) were estimated using mixed-effects models. The residual urine output decreased more rapidly over time in patients with lower hemoglobin levels or higher ERI. Models were adjusted for age, sex, time since dialysis initiation, and log-transformed urine volume at baseline. ESA, erythropoiesis-stimulating agent; ERI, ESA resistance index.

Fig. 3

Association between hemoglobin levels and anuria. Covariates in multivariable adjustment models were as follows: age, sex, time since starting PD, hypertension, urine output at baseline, weekly ESA dose; DM, BMI, history of myocardial infarction, history of stroke, total Kt/V, and smoking (Model 1, a demographic model); Model 1 + TSAT, and ferritin (Model 2, + iron indices); Model 2 + phosphorus, calcium, and intact PTH (Model 3, + CKD-MBD markers); Model 3 + CRP and history of peritonitis (Model 4, + inflammation); Model 4 + albumin and total cholesterol (Model 5, nutritional indices). HR, hazard ratio; CI, confidence interval; ESA, erythropoiesis-stimulating agent; ERI, ESA resistance index; PD, peritoneal dialysis; DM, diabetes mellitus; BMI, body mass index; TSAT, transferrin saturation; PTH, parathyroid hormone; CKD-MBD, chronic kidney disease mineral and bone disorder; CRP, C-reactive protein.

Fig. 4

Non-linear association between ESA resistance index and risk of anuria. Non-linear estimation of residual urine output was demonstrated using restricted cubic spline analysis with three knots at the 10th, 50th, and 90th percentiles of ERI in all patients (A) and in those who were administered ESA (B). The reference category was placed on the median values of ERI, 2.47 (A) and 2.68 (B). A multivariable regression model was adjusted for the variables in Model 5. ESA, erythropoiesis-stimulating agent; ERI, ESA resistance index.