Serum hemoglobin concentration, as a reflection of renal fibrosis, and risk of renal decline in early-stages of diabetic kidney disease: a nationwide, biopsy-based cohort study.

BACKGROUND Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression. METHODS Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at renal biopsy were identified: aged 56 (45, 63); 62.6% men; Hb 13.3 (12.0, 14.5) g/dL; eGFR 76.2 (66.6, 88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio [UACR] 534 (100, 1480) mg/g Crea. Serum hemoglobin concentration were divided into quartiles: ≤12, 12.1-13.3, 13.4-14.5, and ≥14.6 g/dL. The association between serum hemoglobin concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR, or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum hemoglobin concentration to the known risk factors of DKD was assessed. RESULTS Serum hemoglobin levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ =-0.52; P < 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second, and third quartile (the fourth quartile as a reference) were 2.74 (95% CI 1.26-5.97), 2.33 (95% CI 1.07-5.75), and 1.46 (95% CI 0.71-3.64), respectively. Addition of the serum hemoglobin concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global chi-statistics increased from 55.1 to 60.8; P < 0.001). CONCLUSIONS Serum hemoglobin concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease.