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. 2022 Jun 29:2022:2702651.
doi: 10.1155/2022/2702651. eCollection 2022.

Urinary Podocyte Excretion Predicts Urinary Protein Selectivity and Renal Prognosis

Makoto Abe  1 , Akiko Kaiga  1 , Takehiro Ohira  1 , Toshihiko Ishimitsu  1 , Akihiro Tojo  1
Affiliations

Urinary Podocyte Excretion Predicts Urinary Protein Selectivity and Renal Prognosis

Makoto Abe et al. Int J Nephrol. .

Abstract

Background: Urinary podocyte excretion is related to a reduction in glomerular podocyte numbers, glomerulosclerosis, and urinary protein selectivity. To elucidate the role of urinary podocytes in proteinuria and renal prognosis and to identify the factors that cause podocyte detachment, we examined urinary podocytes in 120 renal biopsy patients.

Methods: Podocytes were identified in urinary sediments stained with fluorescent-labeled anti-podocalyxin antibodies in ten high power fields. The amounts of protein bands, separated by SDS-polyacrylamide gel electrophoresis, were calculated using an image software program and the correlation with urinary podocytes was analyzed. Podocyte surface pores were observed using a low-vacuum scanning electron microscope. The renal prognosis, including induction of hemodialysis or 30% reduction in eGFR, was investigated.

Results: Urinary podocyte excretion showed a higher positive correlation with albumin excretion compared to IgG, prealbumin, and transferrin. There were no significant correlations between urinary podocyte count and low molecular weight proteins, including β2-microglobulin and α1-microglobulin. The number of podocyte surface pores was positively correlated with proteinuria, suggesting enhanced albumin transcytosis. The hemodynamic pressure on the glomerular capillary wall, including products of pulse pressure and pulse rate (water hammer pressure), was positively correlated with urinary podocyte excretion. Urinary podocyte excretion and Tamm-Horsfall protein (THP) were independent risk factors for renal prognosis but were not related to response to treatment.

Conclusion: Urinary podocyte excretion was correlated with urinary albumin excretion, indicating specific albumin transport by podocytes. Podocytes were detached from the glomerular capillaries by water hammer pressure and THP was involved in the renal prognosis.

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Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Light microscopy of urinary podocytes (a), immunofluorescence staining for podocalyxin (b), LVSEM observation (c), and PAM staining of the renal biopsy sample of the same patient (d). The arrows indicate podocytes. Bars indicate 10 µm.
Figure 2
Figure 2
Relationship between urinary podocyte excretion and the amount of proteinuria. r = 0.38, p < 0.001 (n = 120).
Figure 3
Figure 3
The correlation between urinary podocyte excretion and urinary protein fractions. The r and p values were as follows: urinary podocytes and IgG, r = 0.34, p < 0.001; Tamm–Horsfall protein (THP), r = 0.34, p < 0.001; transferrin (Tf), r = 0.38, p < 0.001; albumin, r = 0.66, p < 0.001; prealbumin, r = 0.30, p < 0.001; α1-microglobulin, r = 0.02, p=0.84; light chain (LC), r = −0.06, p=0.50; and β2-microglobulin, r = −0.02, p=0.81 (n = 120).
Figure 4
Figure 4
LVSEM observation of podocyte surface pores (a) and the correlation between podocyte pore number and urinary protein excretion (b). r = 0.52, p < 0.005 (n = 31).
Figure 5
Figure 5
Correlation between water hammer pressure × BW and urinary podocyte excretion. r = 0.35, p < 0.001 (n = 120).
Figure 6
Figure 6
Urinary podocyte excretion associated with CKD stages with G1 to G5 as well as with A1 to A3. ∗p < 0.05 and ∗∗p < 0.01 vs. A1, ++p < 0.01 vs. A2.
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