Prognostic Value of Hemoglobin Concentration on Renal Outcomes with Diabetic Kidney Disease: A Retrospective Cohort Study

Abstract

Objective: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated.

Methods: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin.

Results: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521±22.960 g/L. The median follow-up time was 21.103±18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males.

Conclusion: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.

Keywords: Cox proportional-hazards regression; ESRD; diabetic kidney disease; eGFR decline; hemoglobin; non-linear.

Figure 1

Study design and flowchart of study participants.

Figure 2

Showed the distribution of Hb levels. It showed a normal distribution within a range from 56g/L to 187g/L (with an average of 121.5g/L).

Figure 3

The distribution of different eGFR levels and 24hU-alb severity levels with different hemoglobin levels. (A) The relationship between eGFR and Hb in male DKD patients. (B) The relationship between eGFR and Hb in female DKD patients. (C) The relationship between 24hU-alb and Hb in male DKD patients. (D) The relationship between 24hU-alb and Hb in female DKD patients.

Figure 4

Incidence of renal composite endpoint according to Hb quartiles. This figure showed that participants within the highest Hb group had lower incidence rate of renal composite endpoint compared to the group with the lowest Hb (p < 0.0001 for trend).

Figure 5

Kaplan–Meier survival curve. The probability of renal composite endpoint-free survival differed significantly between the Hb quartiles (Log rank test, p < 0.001). The probability of renal composite endpoint-free survival gradually decreased with decreasing Hb, suggesting that the group with the highest Hb had the highest probability of renal composite endpoint-free survival.

Figure 6

The non-linear relationship between Hb and the renal composite endpoint among DKD patients. We used a Cox proportional hazards regression model with cubic spline functions to evaluate the relationship between Hb and renal composite endpoint. The result showed that the relationship between Hb and renal composite endpoint was non-linear, with the inflection point of Hb being 109g/L.