Determination of Urinary Nephrin and Liver type Fatty Acid Binding Protein (L-FABP) levels in diabetic patients with and without nephropathy

Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD) and end-stage renal failure globally. In India, where diabetes prevalence is rapidly increasing, DN represents a major clinical and economic burden. Early diagnosis of DN is critical for effective management and delaying disease progression. Traditionally, microalbuminuria has been used as the gold standard for early detection. However, a significant proportion of patients show renal impairment even in the absence of microalbuminuria (normoalbuminuria), which underscores the need for more sensitive and specific early biomarkers.

Microalbuminuria refers to an increase in urinary albumin excretion between 30–300 mg/day. Although widely used, several studies have shown that microalbuminuria is not always a reliable indicator of early glomerular damage. It can be influenced by factors like physical activity, infection, hypertension, and hydration status. Moreover, some patients with type 2 diabetes may already have histological damage to the kidney before albuminuria is detectable, and some may never develop microalbuminuria despite progressive renal decline.

Nephrin is a key structural protein of the slit diaphragm in podocytes, which plays a vital role in glomerular filtration. Podocyte damage and nephrin shedding into the urine are among the earliest pathological changes in DN. Studies have shown elevated urinary nephrin levels in diabetic patients even before the onset of microalbuminuria, suggesting it as a potential early and specific marker of podocyte injury. A 2021 meta-analysis by Li et al. confirmed significantly elevated urinary nephrin in both microalbuminuric and normoalbuminuric diabetic patients compared to controls. Nephrinuria correlates with the severity of glomerular injury and may precede albuminuria by several months or even years.

L-FABP is expressed in the proximal tubule and is involved in fatty acid transport and intracellular detoxification. Renal tubular stress due to oxidative damage and lipid peroxidation in diabetes leads to increased urinary excretion of L-FABP. Elevated urinary L-FABP levels have been reported in early DN, even in normoalbuminuric patients. Japanese and Korean studies have proposed L-FABP as a sensitive tubular marker, and its combination with albumin improves risk stratification. The 2022 study by Nakamura et al. demonstrated its predictive value for progression to overt proteinuria and decline in eGFR.

Urinary biomarkers are generally preferred in renal disease research due to their non-invasive nature and direct reflection of renal tubular or glomerular pathology. Nephrin and L-FABP are shed into the urine in response to podocyte and tubular injury, respectively. While serum levels can also rise in systemic injury, urinary concentrations offer better organ specificity in this context. Few studies have focused exclusively on the normoalbuminuric diabetic population, despite growing evidence that these individuals are not free from renal risk. The appearance of nephrin and L-FABP in the urine of normoalbuminuric patients suggests that structural damage can precede detectable albuminuria, offering an opportunity for earlier therapeutic intervention.A 2023 cross-sectional study by Sharma et al. reported elevated urinary nephrin and L-FABP in 67% of normoalbuminuric T2DM patients, implying subclinical kidney injury. However, most studies did not combine these markers to analyze their complementary diagnostic potential. Moreover, population-specific validation, particularly from India, is limited.

As this is a non-interventional, observational study, the safety risks are minimal. No drugs or interventions are administered. The only procedures involve 24-hour urine collection and routine clinical data recording. All samples will be anonymized, and data will be stored with restricted access. Participants may benefit from early detection of kidney damage, which could prompt timely medical follow-up.

The existing literature supports urinary nephrin and L-FABP as promising biomarkers for early detection of diabetic nephropathy. However, critical research gaps remain, especially regarding Indian populations and normoalbuminuric patients. The proposed study aims to address these gaps by conducting a focused evaluation of these biomarkers across various stages of diabetes. The findings may lead to earlier diagnosis, improved disease monitoring, and reduced progression to ESRD, thus offering significant clinical and public health benefits.