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Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy - 12/06/24

Doi : 10.1016/j.diabet.2024.101547 
Yue Zhou a, b, 1, Shuang Hou b, 1, Xiao-yan Huang b, Dong-yuan Chang a, Hui Wang a, c, Lin Nie a, c, Zu-ying Xiong b, Min Chen a, Ming-hui Zhao a, Su-xia Wang a, c,
a Division of Nephrology, Peking University First Hospital, Beijing, 100034, PR China 
b Division of Nephrology, Peking University Shenzhen Hospital, Shenzhen, 518000, PR China 
c Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, 100034, PR China 

Corresponding author at: Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, Beijing, 100034, PR ChinaLaboratory of Electron MicroscopyPathological CenterPeking University First HospitalBeijing100034PR China

Highlights

The podocyte foot process width (FPW) and podocyte detachment (PD) are quantifiable podocyte ultrastructural features in diabetic nephropathy (DN), the association between FPW and PD with proteinuria revealed unanimous results.
Higher glomerular classes of DN pathological classification significantly correlate with higher levels of proteinuria and poorer renal prognosis.
FPW broadening and PD are present from the early stages of DN pathological classification (I, IIa).
FPW and PD were associated with the severity of proteinuria and the DN pathological classification, while PD was shown to be a better predictor of proteinuria severity and DN pathological classification in T2DN than FPW.

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Abstract

Aims

Podocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN).

Methods

We collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed.

Results

Mean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017).

Conclusions

Podocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

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Key words : Electron microscopy, Morphometric analysis, Podocyte foot process, Proteinuria, Type 2 diabetic nephropathy

Abbreviations : DN, FPW, GBM, IFTA, M, N, O, PD, RPS, TEM, T1DN, T2DN


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Vol 50 - N° 4

Article 101547- juillet 2024 Retour au numéro
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