Dear Editor,
Anemia resistant to recombinant human erythropoietin (rhEPO) is a risk factor for mortality in patients with chronic kidney disease (CKD) on dialysis11 Suttorp MM, Hoekstra T, Rotmans J, et al. Erythropoiesis-stimulating agent resistance and mortality in hemodialysis and peritoneal dialysis. BMC Nephrol. 2013; 14:200.. Several factors such as uremic toxins, iron deficiency, inflammation, hyperparathyroidism, and medications have been associated with EPO hyporesponsiveness in hemodialysis (HD) patients, but evidence on peritoneal dialysis (PD) is limited22 Predictors of Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Hemodialysis Patients. AJKD 2009; 823-834.. Identifying causes of hyporesponsiveness may help to overcome the resistance in these patients.
We conducted a cross-sectional study involving 50 prevalent PD patients. Patients with acute or chronic inflammatory disease, active malignancy and those not receiving rhEPO therapy were excluded. Patients were treated with weekly darbepoetin alfa to maintain hemoglobin (Hgb) concentration between 10-12 g/dL. To evaluate the dose-response effect of rhEPO therapy, we used the erythropoietin resistance index (ERI), calculated as the mean weekly weight-adjusted dose of rhEPO (U/Kg per week) divided by the mean hemoglobin level (g/dL), over a 3-month period. EPO hyporesponsiveness was defined as an ERI value above the upper quartile (>10), so patients were classified in two groups: ERI≤10 and ERI>10. We compared clinical, analytical, and demographic data among groups. Body composition and fluid volume were evaluated by bioimpedance using the body composition monitor (BCM). Logistic regression analysis was performed to identify predictors of rhEPO hyporesponsiveness. Statistical analysis was executed using SPSS. The mean age of 50 prevalent PD patients was 52.04 ± 15.98 years, 29 (58%) were male, 29 (58%) were diabetic, and 31 (64%) were treated with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). Mean hemoglobin level (Hb) was 10.99 ± 0.81 g/dL and mean ERI was 7.64 ± 7.25. Eleven patients (22%) had hyporesponsiveness to rhEPO therapy (ERI>10). There was no difference among groups for age, gender, etiology of chronic kidney disease, or PD modality. There was also no difference in the use of ACEIs or ARBs. Hyporesponsive patients had lower body mass index (BMI) (22.94 ± 2.89 vs 26.74±4.53 Kg/m2, p=0.01) and lower lean tissue index (LTI) (9.96 ± 1.94 vs 16.23 ± 18.51 Kg/m2, p=0.02), but similar fat tissue index (FTI). Weekly creatinine clearance (peritoneal plus urinary), but not Kt/V, was also significantly lower in this group (68.76 ± 37.29 vs 87.84 ± 35.35 mL/min/1.73m2, p=0.028). Hyporesponsive patients had lower urine volume (0.73 ± 0.63 vs 1.39 ± 0.67 L, p=0.005) and residual kidney function (RKF) (3.43 ± 3.04 vs 6.13 ± 3.69 mL/min/1.73m2, p=0.044). The proportion of patients with fluid overload, defined as overhydration (OH)/extracellular water (ECW) >15%, was significantly higher in this group (p=0.04). No difference between groups was observed in albumin, c-reactive protein, intact parathormone, serum ferritin, or transferrin saturation index. Using a logistic regression analysis, we observed that BMI [(OR) 0.56 (CI: 0.364-0.849)] and LTI [(OR) 0.315 (CI: 0.130-0.767)] were predictors of hyporesponsiveness to rhEPO therapy in an unadjusted model.
In our cohort, body composition, fluid status, and RKF were the main factors that affected the response to rhEPO therapy. In addition to the similarity of our results to those previously described by Penne et al. concerning a strong relationship between RKF and improved phosphate and anemia control in HD patients33 Penne EL, Van der Weerd NC, Grootemen MPC, et al. Role of Residual Renal Function in Phosphate Control and Anemia Management in Chronic Hemodialysis Patients. CJASN 2011, 6 (2) 281-289., our study also shows the importance of euvolemia in the response to rhEPO. The mechanisms underlying these findings are not clear, but we could postulate that they are related to the “inflammatory state” of CKD patients. In our population, factors previously associated with EPO resistance, such as iron status, did not differ significantly between groups. However, these results should be interpreted with caution, since a wide variance in ferritin and TSAT was found in those classified as “hyporesponders”.
Once again, our results support the importance of RKF-preserving strategies and euvolemia maintenance in prevalent PD patients, not only to improve patient and technique survival but also to overcome rhEPO resistance.
References
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1Suttorp MM, Hoekstra T, Rotmans J, et al. Erythropoiesis-stimulating agent resistance and mortality in hemodialysis and peritoneal dialysis. BMC Nephrol. 2013; 14:200.
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2Predictors of Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Hemodialysis Patients. AJKD 2009; 823-834.
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3Penne EL, Van der Weerd NC, Grootemen MPC, et al. Role of Residual Renal Function in Phosphate Control and Anemia Management in Chronic Hemodialysis Patients. CJASN 2011, 6 (2) 281-289.
Publication Dates
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Publication in this collection
25 July 2022 -
Date of issue
Jan-Mar 2023
History
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Received
01 Feb 2022 -
Accepted
11 May 2022
