Microproteinuria to Macroproteinuria as a Dynamic Indicator of Glomerular Injury in Obesity-Related Kidney Disease

Abstract

Obesity-related kidney disease has emerged as a major contributor to the global burden of chronic kidney disease in recent decades. The rapid increase in obesity prevalence worldwide has uncovered renal complications that occur independently of diabetes mellitus and systemic hypertension. Among the earliest manifestations of obesity-induced renal injury is proteinuria, which reflects progressive dysfunction of the glomerular filtration barrier. The progression from microproteinuria to macroproteinuria represents a dynamic continuum of glomerular damage rather than a rigid clinical threshold. Microproteinuria indicates early and potentially reversible alterations in glomerular permeability caused by hemodynamic stress, adipokine imbalance, low-grade inflammation, and oxidative injury. Persistent exposure to these pathological stimuli promotes podocyte dysfunction, basement membrane remodeling, and mesangial expansion, ultimately leading to sustained protein leakage and macroproteinuria. This advanced stage of proteinuria signifies irreversible structural injury and is strongly associated with accelerated renal function decline and increased cardiovascular morbidity. Importantly, proteinuria acts not only as a biomarker of kidney damage but also as an active mediator of tubulointerstitial inflammation and fibrosis, thereby amplifying disease progression. Monitoring the transition from microproteinuria to macroproteinuria provides valuable insight into disease activity, prognosis, and therapeutic response. This review critically examines the mechanisms linking obesity to glomerular injury, with emphasis on proteinuria as a dynamic indicator of renal damage. Understanding this progression may enable earlier diagnosis, improved risk stratification, and timely interventions to mitigate obesity-related kidney disease.