Nonproteinuric Versus Proteinuric Phenotypes in Diabetic Kidney Disease: A Propensity Score-Matched Analysis of a Nationwide, Biopsy-Based Cohort Study

Abstract

Objective: Clinicopathological characteristics, renal prognosis, and mortality in patients with type 2 diabetes and reduced renal function without overt proteinuria are scarce.

Research design and methods: We retrospectively assessed 526 patients with type 2 diabetes and reduced renal function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²), who underwent clinical renal biopsy and had follow-up data, from Japan's nationwide multicenter renal biopsy registry. For comparative analyses, we derived one-to-two cohorts of those without proteinuria versus those with proteinuria using propensity score-matching methods addressing the imbalances of age, sex, diabetes duration, and baseline eGFR. The primary end point was progression of chronic kidney disease (CKD) defined as new-onset end-stage renal disease, decrease of eGFR by ≥50%, or doubling of serum creatinine. The secondary end point was all-cause mortality.

Results: Eighty-two patients with nonproteinuria (urine albumin-to-creatinine ratio [UACR] <300 mg/g) had lower systolic blood pressure and less severe pathological lesions compared with 164 propensity score-matched patients with proteinuria (UACR ≥300 mg/g). After a median follow-up of 1.9 years (interquartile range 0.9-5.0 years) from the date of renal biopsy, the 5-year CKD progression-free survival was 86.6% (95% CI 72.5-93.8) for the nonproteinuric group and 30.3% (95% CI 22.4-38.6) for the proteinuric group (log-rank test P < 0.001). The lower renal risk was consistent across all subgroup analyses. The all-cause mortality was also lower in the nonproteinuric group (log-rank test P = 0.005).

Conclusions: Patients with nonproteinuric diabetic kidney disease had better-controlled blood pressure and fewer typical morphological changes and were at lower risk of CKD progression and all-cause mortality.