Introduction: Smoking-related nodular glomerulosclerosis (SRNG) is a distinct clinicopathologic entity that resembles diabetic nephropathy but occurs in patients without diabetes, often associated with longterm smoking and hypertension.Approximately 40% of SRNG patients progress to end-stage renal disease (ESRD) within five years.Recent studies from our department demonstrated marked overexpression of advanced glycation end products (AGEs) and their receptor (RAGE) in glomeruli and arterial walls of SRNG patients.Smoking cessation may reduce endogenous AGE formation caused by oxidative stress and decrease exogenous AGEs from tobacco smoke, thereby improving endothelial function.In vitro, AGEs increase SGLT2 and RAGE expression in podocytes, along with inflammatory cytokine production, whereas dapagliflozin ameliorates these effects.We report a case of SRNG in which proteinuria improved following smoking cessation and SGLT2 inhibitor administration.Methods: A man in his 70s presented with generalized edema.Since August 20XX, he had developed progressive edema and weight gain, which worsened in October, prompting medical consultation.Laboratory tests showed serum albumin 2.3 g/dL, serum creatinine 1.76 mg/ dL, and urine protein-to-creatinine ratio (UP/UCr) 13.0 g/gCr, consistent with nephrotic syndrome and renal dysfunction.He was admitted to our department in November for further evaluation.Kidney biopsy revealed diffuse mesangial matrix expansion with multiple nodular and exudative lesions.Immunofluorescence staining was negative for immunoglobulins and complement.Despite the diabetic-like glomerular morphology, he did not meet criteria for diabetes mellitus.Considering his long smoking history, a diagnosis of SRNG was made.Results: Treatment with azosemide 30 mg, irbesartan 100 mg, and spironolactone 25 mg was continued, and empagliflozin 10 mg was added in combination with smoking cessation.Subsequently, his edema improved, serum albumin rose to 3.1 g/dL, serum creatinine stabilized at 1.98 mg/dL, and UP/UCr markedly decreased to 2.21 g/ gCr. Conclusion:We experienced a case of nephrotic syndrome with diabetic nephropathy-like lesions confirmed by renal biopsy, ultimately diagnosed as SRNG.The patient demonstrated significant improvement in proteinuria after smoking cessation and treatment with an SGLT2 inhibitor in addition to renin-angiotensin system blockade.Based on prior evidence of AGEs and RAGE overexpression in SRNG, it is likely that smoking cessation reduced both oxidative stress-related and exogenous AGEs, while SGLT2 inhibition attenuated RAGE-mediated inflammatory signaling in podocytes.Together, these mechanisms may have contributed to the observed reduction in proteinuria.To our knowledge, this is the first reported case showing improvement of proteinuria in SRNG with the combination of smoking cessation and SGLT2 inhibition, highlighting a potential therapeutic approach for this entity.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.
MURAMATSU et al. (Wed,) studied this question.