Abstract
BACKGROUND: Podocytic injury and shedding are critical events in the progression and prognosis of diabetic nephropathy (DN). The purpose of our study was to observe heterokaryotic podocytes caused by mitotic catastrophe and the levels of murine double minute gene 2 (MDM2) and synaptopodin (SP) in the urine of patients with diabetic kidney disease (DKD) to explore their value as markers in the early diagnosis of DKD. METHODS: We examined urine samples from diabetic patients, determined the presence of urinary podocytes and podocyte mitosis catastrophe (PMC), and analyzed their correlations with numerous indicators. Podocytes in urine sediment were observed and counted using immunofluorescence (IF), and the expression of MDM2 and SP in urine supernatant was detected using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Podocytes might have been damaged in diabetic patients even during the period of normal albuminuria. Urinary SP level was positively correlated with urinary and heterolytic podocyte counts. MDM2 upregulation in urine was consistent with an increase in albuminuria level and heterolytic podocyte count. The sensitivity of urinary MDM2 to creatine (MDM2/Cr) in the diagnosis of DKD was high, as was the specificity of urinary SP to creatinine (SP/Cr). The diagnostic efficacy of combined urinary MDM2/Cr and SP/Cr was higher than that of either one alone. CONCLUSION: We observed that PMC and elevated urinary MDM2/Cr levels emerged early in DKD. Additionally, we developed a diagnostic panel combining urinary MDM2/Cr and SP/Cr, which might serve as a predictive tool for early DKD diagnosis and prevention.