Urinary nephrin is earlier, more sensitive and specific marker of diabetic nephropathy than microalbuminuria

J Med Biochem. 2020 Jan 10;39(1):83-90. doi: 10.2478/jomb-2019-0026.

Abstract

Background: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Progressive damage and decline in the number of podocytes often occur in the early stages of DN. Thus, nephrin as a podocyte-specific protein may be regarded as a potential biomarker of early detection of DN. The aim of this study is to determine whether urinary nephrin is an earlier marker in DN than microalbuminuria and to test the significance of urinary nephrin as a marker for early detection of DN.

Methods: Our cross-sectional study included 90 patients with type 2 diabetes mellitus (T2DM), 30 patients with diagnosed DN and 60 patients without diagnosed DN. As a control group, we used 30 healthy subjects. All patients with T2DM were classified into three subgroups according to urinary microalbumin/creatinine ratio (UMCR): normoalbuminuric, microalbuminuric and macroalbuminuric patients. Nephrin in urine was measured by immunoenzyme assay, microalbumin with turbidimetric and creatinine with the photometric method. In blood sera, we measured a few standard biochemical parameters.

Results: Nephrinuria was found to be present in 100% of patients with T2DM and macroalbuminuria, in 88% with microalbuminuria, as well as 82% of patients with T2DM and normoalbuminuria. A concentration of urinary nephrin was significantly increased in all groups of subjects with T2DM compared to the control group (p<0.05). Nephrinuria correlated statistically negative with eGFR (r=-0.54). ROC analysis showed that nephrin has a total predicted probability of 96% in patients with DN.

Conclusions: Urinary nephrin is earlier, more specific and sensitive marker than microalbumin in early detection of DN.

Uvod: Dijabetesna nefropatija (DN) je vodeći uzrok završnog stadijuma bubrežne bolesti. Progresivno oštećenje i opadanje broja podocita često se javlja u ranim fazama DN, tako da se nefrin kao specifični protein podocita može smatrati potencijalnim biomarkerom ranog otkrivanja DN. Cilj ove studije je da utvrdi da li je urinarni nefrin raniji marker DN u odnosu na mikroalbuminuriju i da testira značaj urinarnog nefrina kao markera za rano otkrivanje DN.

Metode: Naša studija preseka je obuhvatila 90 pacijenata sa dijabetesom tipa 2 (T2DM), 30 bolesnika sa dijagnozom DN i 60 pacijenata bez dijagnoze DN. Za kontrolnu grupu smo koristili 30 zdravih ispitanika. Svi bolesnici sa T2DM kla sifikovani su u tri podgrupe prema odnosu urinarnog mikro albumina/kreatinina (UMCR): normoalbuminurni, mikro albuminurni i makroalbuminurni pacijenti. Nefrin u urinu je meren imunoenzimskim testom, mikroalbumin uz korišćenje turbidimetrijske i kreatinin koristeći foto metrijsku metodu. U krvnim serumima, merili smo nekoliko standardnih biohemijskih parametara.

Rezultati: Ustanovljeno je da je nefrinurija prisutna u 100% pacijenata sa T2DM i makroalbuminurijom, u 88% sa mikro albuminurijom, kao i 82% pacijenata sa T2DM i normoalbuminurijom. Koncentracija urinarnog nefrina značajno je povećana u svim grupama ispitanika sa T2DM u poređenju sa kontrolnom grupom (p < 0,05). Nefrinurija je korelirala statistički negativno sa eGFR (r = -0,54). ROC analiza je pokazala da je kod pacijenata sa DN ukupna predviđena verovatnoća nefrina 96%.

Zaključak: Urinarni nefrin je raniji, specifičniji i osjetljiviji marker od mikroalbumina u ranom otkrivanju DN.

Keywords: diabetic nephropathy; microalbumin; nephrin.