Increased Urinary Excretion of Podocyte Markers in Normoalbuminuric Patients with Diabetes

Abstract

Background: Podocyte injury plays a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). We investigated whether patients with diabetes mellitus (DM) without overt DN present podocyte markers in urine suggestive of early podocyte injury. Methods: We studied 71 patients with DM type 2 and normal urine albumin excretion (UAE) and 39 non-diabetic controls. The mRNA abundance of 3 podocyte-specific markers in urinary sediment (nephrin, podocin and synaptopodin) was measured with real-time quantitative PCR. All the subjects were categorized according to their urinary podocyte marker profile into 2 groups, those with only synaptopodin mRNA presence (synaptopodin only group) and those with nephrin and/or podocin mRNA presence in addition to synaptopodin in their urine (nephrin and/or podocin group). Results: Synaptopodin mRNA was detected in the urine of all the diabetics and controls. The presence of nephrin and/or podocin mRNA in urine was more frequent among DM patients compared to controls (53.5 vs. 30.8%, respectively; p = 0.022). Binary logistic regression analysis revealed that the only significant predictor of the presence of nephrin and/or podocin mRNA in urine was the presence of DM (OR 2.59, 95% CI 1.14-5.91, p = 0.024, adjusted for all risk factors). A strong correlation between nephrin and podocin urinary mRNA levels was noted (r = +0.796, p < 0.001). Conclusion: This study demonstrated that urinary podocyte markers are more prevalent in diabetic patients with normal UAE compared to controls, and this may reflect early podocyte injury. DM is the only significant determinant of the presence of nephrin and/or podocin mRNA in urine in this population. Therefore, urinary podocyte markers may emerge as a valuable tool in the early diagnosis of DN.

Urinary podocyte-associated mRNA levels correlate with proximal tubule dysfunction in early diabetic nephropathy of type 2 diabetes mellitus

“…In our study, all seven podocyte-associated molecules correlated directly with albuminuria even in normoalbuminuric patients, similarly with the results provided by other studies [32–35]. This correlation is highly indicative of significant podocyturia and allows for a non-invasive diagnosis of podocyte loss into urine in early DN.…”

“…A recent study carried out in normoalbuminuric patients with type 2 DM revealed increased levels of urinary podocyte markers, such as synaptopodin, nephrin, and podocin, an observation which reflects early podocyte injury [35]. …”

Association between Renal Podocalyxin Expression and Renal Dysfunction in Patients with Diabetic Nephropathy: A Single-Center, Retrospective Case-Control Study

“…Proteinuria is closely associated with the prognosis of patients with DN. Recent studies concluded that podocyte damage plays a vital role in the pathogenesis of DN [13,21]. Podocytes are located in the outer layer of the GBM and help maintain the integrity of the Glycated products are involved in the pathogenesis of T2DM, and HbA1c levels are a recognized marker of glycemic control in patients with T2DM [22,23].…”

“…Studies in recent years have shown that damage to podocytes plays an essential role in the pathogenesis of DN [13].…”

Urinary podocin level as a predictor of diabetic kidney disease

“…Moreover, Lioudaki et al (14) revealed that urinary podocyte markers (nephrin, podocin, and synaptopodin) were more elevated in normoalbuminuric DM patients in comparison to non-diabetic controls. Urinary podocin was detected in diabetic patients with normal or increased GFR and was significantly and negatively correlated with GFR.…”