Published online Dec 25, 2025. doi: 10.5527/wjn.v14.i4.111613
Revised: August 3, 2025
Accepted: November 7, 2025
Published online: December 25, 2025
Processing time: 172 Days and 8.6 Hours
Diabetic patients with atypical presentation are often challenging in terms of diagnosis and management. Kidney biopsy is not routinely done in diabetics, and clinicians are always in a dilemma in such a scenario to decide whether to do a biopsy or not. Since non-diabetic kidney diseases (NDKD) are common, and some patients may have NDKD superimposed on diabetic kidney diseases (DKD), therefore, kidney biopsy may be warranted to rule out NDKD.
To determine the prevalence of NDKD, DKD, or mixed lesions, identify predictors of NDKD, and investigate renal and patient survival, as well as factors associated with these outcomes.
This retrospective observational study was conducted on patients with biopsy-proven NDKD, DKD, and mixed lesions (having both NDKD and DKD). Binary logistic regression models were constructed to identify predictors of NDKD. Kaplan-Meier survival analysis was performed to compare time to kidney failure and patient survival across the three histological groups. Multivariable Cox proportional hazards regression was used to identify clinical and pathological factors associated with kidney failure and all-cause mortality.
A total of 103 biopsies were analyzed. Sixty-four (62.1%) had NDKD alone or mixed lesions. The most common NDKD pathologies were interstitial nephritis in 12 (29.2%), focal segmental glomerulosclerosis in 10 (24.4%), and immune complex–mediated glomerulonephritis in five (12.2%) patients. Compared to DKD, NDKD was associated with significantly lower odds of proteinuria > 3.5 g/day [odds ratio (OR), 0.02; P = 0.0015], retinopathy (OR = 0.04; P = 0.0067), and diabetes duration ≥ 10 years (OR = 0.01; P = 0.0002). However, NDKD had higher odds of anemia (Hemoglobin < 12 g/dL; OR = 9.56; P = 0.0107) and creatinine levels > 180 μmol/L (OR = 18.68; P = 0.0063). Kaplan-Meier analysis showed significant differences in renal survival (log-rank P = 0.0033). Patients with NDKD have the best outcomes, while those with DKD have the worst. In a multivariable Cox regression analysis, increasing age, creatinine, arteriosclerosis, and severe interstitial fibrosis and tubular atrophy were independently associated with kidney failure. At the same time, the use of renin angiotensin system blockers was protective (hazard ratio = 0.43, P = 0.02). Kaplan-Meier curves for patient survival also differed significantly (log-rank P = 0.018); patients in the mixed group showed the highest mortality, while those with NDKD showed the lowest. Mortality was independently associated with older age, hypoalbuminemia, diabetic retinopathy, arteriosclerosis, and higher creatinine.
NDKD and mixed lesions are frequent in diabetic patients. These histological lesions carry distinct prognostic implications. Clinical features such as a shorter diabetes duration, absence of retinopathy, anemia, and elevated creatinine levels suggest NDKD and warrant biopsy. NDKD had better renal and patient survival rates, while mixed lesions had the worst outcomes. Older age, hypoalbuminemia, retinopathy, arteriosclerosis, and elevated creatinine were key predictors of mortality.
Core Tip: Diabetic patients have non-diabetic kidney diseases (NDKD) alone or with diabetic kidney diseases (DKD) in 62.1%. Compared to DKD, NDKD was associated with significantly lower odds of heavy proteinuria, retinopathy, and long-standing diabetes. However, NDKD had higher odds of anemia. NDKD patients experienced better renal and patient survival outcomes. Increasing age, creatinine, arteriosclerosis, interstitial fibrosis, and tubular atrophy were independently associated with kidney failure. Renin angiotensin system blockers were found to be protective in preventing kidney failure. Mortality was independently associated with older age, hypoalbuminemia, diabetic retinopathy, arteriosclerosis, and higher creatinine.