PMC10050546_01
(A) Pedigree. (B) Kidney biopsy displayed 17 glomeruli, seven glomerular scars, and two arteries. The glomeruli had a clear and nodular mesangial matrix expansion, a focal and low-grade mesangial hypercellularity, and segmental hyaline lesions. Arteries demonstrated a discrete intimal expansion, whereas arterioles showed a major transmural hyalinosis with significant luminal narrowing. A diffuse and variable, often prominent, interstitial fibrosis with tubular atrophy, accompanied by a low-grade lymphomononuclear interstitial infiltrate and a slight tubular cell dystrophy with regenerative changes, was noticeable. The immunohistochemistry only showed IgM and C1q deposits in sclerosed glomerular portions. These findings were consistent with advanced diabetic nephropathy with nodular glomerulosclerosis, significant arteriolosclerosis, and major interstitial fibrosis with tubular atrophy. The electron microscopic examination of a partially sclerotic glomerulus confirmed glomerular changes compatible with diabetic damage, exhibiting pauci-cellular mesangial expansion, broadened capillary basal membranes due to an enlarged lamina densa, and some double contours. Podocyte structures showed flattened pedicels in the rare non-sclerotic segments. Additionally, some subendothelial electron-dense and often electron-lucent areas consistent with partially dissolving immune deposits suggested a concomitant and resolving immune complex glomerulonephritis. (C) Laboratory results and treatment details; creatinine, mg/dL; HbA1c, %; ACR, albumin-to-creatinine ratio, g/g; PCR, protein-to-creatinine ratio, g/g; eGFR, estimated glomerular filtration rate, mL/min per 1.73 m2; IFCC, HbA1c IFCC, mmol/mol.
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F1
His family history disclosed several relatives with a diagnosis of diabetes not characteristic of type 1 or 2, many of them living in Syria (the pedigree of this family is shown in Figure 1A). In 2022, at the age of 25 years, a kidney biopsy showed severe nodular glomerulosclerosis (the kidney biopsy is shown in Figure 1B). Notably, glycemic control was not achieved with insulin therapy alone and markedly improved after definitive genetic diagnosis and the addition of a sulfonylurea (Figure 1C ).