Nephrinuria and podocytopathies.

The discovery of nephrin in 1998 has launched a new era in glomerular diseases research, emphasizing its crucial role in the structure and function of the glomerular filtration barrier. In the past 20 years, substantial advances have been made in understanding podocyte structure and function as well as the discovery of several podocyte-related proteins including nephrin. The glomerular filtration barrier is comprised of podocytes, the glomerular basement membrane and endothelial cells. Podocytes, with their specialized slit diaphragm, form the essential backbone of the glomerular filtration barrier. Nephrin is a crucial structural and functional feature of the slit diaphragm that prevents plasma protein, blood cell and macromolecule leakage into the urine. Podocyte damage results in nephrin release. Podocytopathies are kidney diseases in which podocyte damage drives proteinuria, i.e., nephrotic syndrome. Many kidney diseases involve podocytopathy including congenital nephrotic syndrome of Finnish type, diffuse mesangial sclerosis, minimal change disease, focal segmental glomerulosclerosis, collapsing glomerulonephropathy, diabetic nephropathy, lupus nephropathy, hypertensive nephropathy and preeclampsia. Recently, urinary nephrin measurement has become important in the early detection of podocytopathies. In this chapter, we elaborate the main structural and functional features of nephrin as a podocyte-specific protein, pathomechanisms of podocytopathies which result in nephrinuria, highlight the most commonly used methods for detecting urinary nephrin and investigate the diagnostic, prognostic and potential therapeutic relevance of urinary nephrin in primary and secondary proteinuric kidney diseases.

Role of urinary podocalyxin in early diagnosis of diabetic nephropathy.

Introduction. Podocyte injury has been reported as an early feature of DN therefore, the assessment of podocyte injury can be accomplished by estimation of podocalyxin in urine. This study aimed to estimate the urinary podocalyxin levels and to determine the sensitivity and specificity of this biomarker for early detection of DN.Materials and methods. A total of 90 patients with type 2 diabetes mellitus (T2DM) were included in this cross-sectional study. Sixty of them were without diagnosed DN, and 30 with diagnosed DN. A control group consisted of 30 healthy subjects. All patients with T2DM were divided into three subgroups according to urinary microalbumin/creatinine ratio (UM/CR): normoalbuminuric, microalbuminuric and macroalbuminuric patients. Urine samples, were used for measurement of podocalyxin by ELISA, creatinine and microalbumin. Fasting venous blood samples was collected for biochemical analyses.Results. The levels of urinary podocalyxin (u-PDX) were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied subgroups regarding u-PDX was found (p < 0.05). Levels of u-PDX are increasing gradually with the degree of DN (p < 0.029). u-PDX levels were positively correlated with UM/CR (r = 0.227, p = 0.002). A cut-off level of 43.8 ng/ml u-PDX showed 73.3% sensitivity and 93.3% specificity to detect DN in early stage. A cut-off level of 30 mg/g UM/CR showed 41.5% sensitivity and 90% specificity in predicting DN. u-PDX was elevated in 48,2% of normoalbuminuric patients.Conclusion. Urinary podocalyxin be useful and more sensitive and specific marker in early detection of DN than microalbuminuria.