Anemia in Diabetic Patients Reflects Severe Tubulointerstitial Injury and Aids in Clinically Predicting a Diagnosis of Diabetic Nephropathy

Abstract

Objective A kidney biopsy is generally performed in diabetic patients to discriminate between diabetic nephropathy (DN) and non-diabetic kidney disease (NDKD) and to provide more specific treatments. This study investigated the impact of anemia on the renal pathology and the clinical course in patients who underwent a kidney biopsy. Methods We reviewed 81 patients with type 2 diabetes who underwent a percutaneous kidney biopsy. Patients were classified into two groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD group, n=51) groups. The laboratory and pathological findings and clinical courses were investigated. Results In the NDKD group, membranous nephropathy was the most common finding (23.5%), followed by IgA nephropathy (17.6%) and crescentic glomerulonephritis (13.7%). In the logistic regression analysis, the absence of severe hematuria and presence of anemia were significantly associated with a diagnosis of DN. Akaike's information criterion (AIC) and net reclassification improvement (NRI) analyses revealed improved predictive performance by adding anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of patients in the DN group demonstrated more severe interstitial fibrosis and tubular atrophy (IF/TA) than those in the NDKD group (p<0.05) regardless of the rate of global glomerulosclerosis, and IF/TA was related to the prevalence of anemia (odds ratio: 7.31, 95% confidence interval: 2.33-23.00, p<0.01) according to a multivariable regression analysis. Furthermore, the isolated DN group demonstrated a poorer prognosis than the NDKD group. Conclusion DN is associated with anemia because of severe IF/TA regardless of the renal function, and anemia helps clinician discriminate clinically between isolated DN and NDKD.

Keywords: interstitial fibrosis; non-diabetic renal diseases; percutaneous kidney biopsy; renal anemia; retinopathy.

Figure 1.

An ROC analysis for the prediction of isolated DN. Model 1 shows the receiver operating characteristics curve obtained from conventional predictive factors consisting of a long duration of diabetes mellitus, diabetes retinopathy (DR), and the absence of severe hematuria. Model 2 shows the factors used in model 1+anemia. p=0.057, log-rank test. ROC: receiver operating characteristic, DN: diabetic nephropathy

Figure 2.

Glomerular and tubulointerstitial damage of kidney biopsy specimens. a: The percentage of glomeruli that showed global sclerosis in the isolated diabetic nephropathy (DN) group (black line) and the non-diabetic kidney disease (NDKD) group (gray line); the error bar indicates the standard deviation. b: The distribution of the grade of tubulointerstitial damage in the isolated DN group (black dots) and NDKD group (gray dots). *The result of the χ² test was statistically significant (p<0.05).

Figure 3.

Relationship between the renal pathology and the renal survival (a, b), and mortality (c, d). a, c: Kaplan-Meier curve according to the isolated DN group (black line) and NDKD group (gray line). b, d: Kaplan-Meier curve according to the isolated DN (black solid line), NDKD with concurrent DN (NDKD+DN, gray dashed line), and NDKD alone (gray solid line) groups. *There was a significant difference in the comparison between the NDKD alone and isolated DN groups (p<0.017, Log rank test after Bonferroni correction). DN: diabetic nephropathy, NDKD: non-diabetic kidney disease