LAUSR

Arterial hypertension (aHTN) and diabetes mellitus type 2 (DM2) are key drivers of chronic kidney disease (CKD). Both HTN and DM2 lead to hyperfiltration with subsequent glomerulomegaly and podocyte depletion. These structural changes in turn lead to glomerulosclerosis and CKD progression. This retrospective study aimed to assess glomerular and podocyte alterations in patients with aHTN and explore the additive effects of coexisting DM2. Morphometric analyses on glomerular and podocyte structure were performed on unaffected kidney regions from tumor nephrectomy specimens of 99 patients. The cohort was divided into three groups: aHTN only (n=47), aHTN+DM2 (n=32), and controls without aHTN or DM2 (n=20). Glomerular and podocyte characteristics were compared using analysis of variance. Multivariable linear regression examined the influence of glomerular- and podometrics on renal compensatory capacity, defined as the change in estimated glomerular filtration rate (∆eGFR) from the presurgical baseline to 12 months after nephrectomy. Proteinuria was observed in 36% of patients with aHTN and 50% of those with aHTN+DM2. There was no difference in glomerular volume between the aHTN+DM2 group and controls (2.7±0.8 vs. 2.3±0.8 ×10⁶ μm³; P=0.16), and to aHTN alone (2.7±0.9 ×10⁶ μm³; P=0.95). Individuals with aHTN+DM2 showed a lower podocyte density compared to controls (217±66 vs. 279±75 per 10⁶ μm³; P=0.02) but no difference to aHTN alone (233±87 per 10⁶ μm³; P=0.67). Subjects with aHTN+DM2 exhibited podocyte nuclear hypertrophy compared to controls (230±28 μm³ vs. 201±32 μm³; P=0.004), and did not differ significantly from the aHTN group (221±33 μm³; P=0.39). Glomerular enlargement (P=0.009) decreased podocyte density (P=0.003), and larger podocyte nuclei (P=0.01) correlated with reduced compensation of eGFR. Relative podocyte depletion and nuclear hypertrophy were evident in both aHTN and aHTN+DM2. However, the presence of DM2 in individuals with aHTN did not exert additional structural changes beyond those observed with aHTN alone. Morphometric parameters like glomerular volume, podocyte density, and podocyte nuclear volume could be estimated in patients undergoing nephrectomy (either oncologic, traumatic, or living kidney donation) to identify individuals at risk for impaired renal compensation, which require close monitoring of kidney function.