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Published in: BMC Nephrology 1/2024

Open Access 01-12-2024 | Chronic Kidney Disease | Research

Urinary podocyte stress marker as a prognostic indicator for diabetic kidney disease

Authors: Lingfeng Zeng, Jack Kit-Chung Ng, Winston Wing-Shing Fung, Gordon Chun-Kau Chan, Kai-Ming Chow, Cheuk-Chun Szeto

Published in: BMC Nephrology | Issue 1/2024

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Abstract

Background

Diabetic kidney diseases (DKD) is a the most common cause of end-stage kidney disease (ESKD) around the world. Previous studies suggest that urinary podocyte stress biomarker, e.g. podocin:nephrin mRNA ratio, is a surrogate marker of podocyte injury in non-diabetic kidney diseases.

Method

We studied 118 patients with biopsy-proved DKD and 13 non-diabetic controls. Their urinary mRNA levels of nephrin, podocin, and aquaporin-2 (AQP2) were quantified. Renal events, defined as death, dialysis, or 40% reduction in glomerular filtration rate, were determined at 12 months.

Results

Urinary podocin:nephrin mRNA ratio of DKD was significantly higher than the control group (p = 0.0019), while urinary nephrin:AQP2 or podocin:AQP2 ratios were not different between groups. In DKD, urinary podocin:nephrin mRNA ratio correlated with the severity of tubulointerstitial fibrosis (r = 0.254, p = 0.006). and was associated with the renal event-free survival in 12 months (unadjusted hazard ratio [HR], 1.523; 95% confidence interval [CI] 1.157–2.006; p = 0.003). After adjusting for clinical and pathological factors, urinary podocin:nephrin mRNA ratio have a trend to predict renal event-free survival (adjusted HR, 1.327; 95%CI 0.980–1.797; p = 0.067), but the result did not reach statistical significance.

Conclusion

Urinary podocin:nephrin mRNA ratio has a marginal prognostic value in biopsy-proven DKD. Further validation is required for DKD patients without kidney biopsy.
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Literature
3.
go back to reference Ishii H, Kaneko S, Yanai K, Aomatsu A, Hirai K, Ookawara S, Ishibashi K, Morishita Y. MicroRNAs in Podocyte Injury in Diabetic Nephropathy. Front Genet. 2020;11:993.CrossRefPubMedPubMedCentral Ishii H, Kaneko S, Yanai K, Aomatsu A, Hirai K, Ookawara S, Ishibashi K, Morishita Y. MicroRNAs in Podocyte Injury in Diabetic Nephropathy. Front Genet. 2020;11:993.CrossRefPubMedPubMedCentral
5.
go back to reference Kravets I, Mallipattu SK. The role of podocytes and podocyte-associated biomarkers in diagnosis and treatment of diabetic kidney disease. J Endocr Soc. 2020;4(4):bvaa029.CrossRefPubMedPubMedCentral Kravets I, Mallipattu SK. The role of podocytes and podocyte-associated biomarkers in diagnosis and treatment of diabetic kidney disease. J Endocr Soc. 2020;4(4):bvaa029.CrossRefPubMedPubMedCentral
6.
7.
go back to reference Sato Y, Wharram BL, Lee SK, Wickman L, Goyal M, Venkatareddy M, Chang JW, Wiggins JE, Lienczewski C, Kretzler M, Wiggins RC. Urine podocyte mRNAs mark progression of renal disease. J Am Soc Nephrol. 2009;20(5):1041–52.CrossRefPubMedPubMedCentral Sato Y, Wharram BL, Lee SK, Wickman L, Goyal M, Venkatareddy M, Chang JW, Wiggins JE, Lienczewski C, Kretzler M, Wiggins RC. Urine podocyte mRNAs mark progression of renal disease. J Am Soc Nephrol. 2009;20(5):1041–52.CrossRefPubMedPubMedCentral
8.
go back to reference Wang G, Lai FM, Lai KB, Chow KM, Kwan BC, Li KT, Szeto CC. Intra-renal and urinary mRNA expression of podocyte-associated molecules for the estimation of glomerular podocyte loss. Ren Fail. 2010;32(3):372–9.CrossRefPubMed Wang G, Lai FM, Lai KB, Chow KM, Kwan BC, Li KT, Szeto CC. Intra-renal and urinary mRNA expression of podocyte-associated molecules for the estimation of glomerular podocyte loss. Ren Fail. 2010;32(3):372–9.CrossRefPubMed
9.
go back to reference Wang G, Lai FM, Kwan BC, Lai KB, Chow KM, Li PK, Szeto CC. Podocyte loss in human hypertensive nephrosclerosis. Am J Hypertens. 2009;22(3):300–6.CrossRefPubMed Wang G, Lai FM, Kwan BC, Lai KB, Chow KM, Li PK, Szeto CC. Podocyte loss in human hypertensive nephrosclerosis. Am J Hypertens. 2009;22(3):300–6.CrossRefPubMed
10.
go back to reference Fukuda A, Wickman LT, Venkatareddy MP, Wang SQ, Chowdhury MA, Wiggins JE, Shedden KA, Wiggins RC. Urine podocin:nephrin mRNA ratio (PNR) as a podocyte stress biomarker. Nephrol Dial Transplant. 2012;27(11):4079–87.CrossRefPubMedPubMedCentral Fukuda A, Wickman LT, Venkatareddy MP, Wang SQ, Chowdhury MA, Wiggins JE, Shedden KA, Wiggins RC. Urine podocin:nephrin mRNA ratio (PNR) as a podocyte stress biomarker. Nephrol Dial Transplant. 2012;27(11):4079–87.CrossRefPubMedPubMedCentral
11.
go back to reference Naik AS, Le D, Aqeel J, Wang SQ, Chowdhury M, Walters LM, Cibrik DM, Samaniego M, Wiggins RC. Podocyte stress and detachment measured in urine are related to mean arterial pressure in healthy humans. Kidney Int. 2020;98(3):699–707.CrossRefPubMedPubMedCentral Naik AS, Le D, Aqeel J, Wang SQ, Chowdhury M, Walters LM, Cibrik DM, Samaniego M, Wiggins RC. Podocyte stress and detachment measured in urine are related to mean arterial pressure in healthy humans. Kidney Int. 2020;98(3):699–707.CrossRefPubMedPubMedCentral
12.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. CKD-EPI (chronic kidney disease epidemiology collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. CKD-EPI (chronic kidney disease epidemiology collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.CrossRefPubMedPubMedCentral
13.
go back to reference Kostovska I, Tosheska-Trajkovska K, Topuzovska S, Cekovska S, Spasovski G, Kostovski O, Labudovic D. Urinary nephrin is earlier, more sensitive and specific marker of diabetic nephropathy than microalbuminuria. J Med Biochem. 2020;39(1):83–90.PubMedPubMedCentral Kostovska I, Tosheska-Trajkovska K, Topuzovska S, Cekovska S, Spasovski G, Kostovski O, Labudovic D. Urinary nephrin is earlier, more sensitive and specific marker of diabetic nephropathy than microalbuminuria. J Med Biochem. 2020;39(1):83–90.PubMedPubMedCentral
14.
go back to reference Wang G, Szeto CC. Methods of microRNA quantification in urinary sediment. Methods Mol Biol. 2013;1024:211–20.CrossRefPubMed Wang G, Szeto CC. Methods of microRNA quantification in urinary sediment. Methods Mol Biol. 2013;1024:211–20.CrossRefPubMed
15.
go back to reference Wang G, Lai FM, Chow KM, Kwan BC, Pang WF, Luk CC, Leung CB, Li PK, Szeto CC. Urinary mRNA levels of ELR-negative CXC chemokine ligand and extracellular matrix in diabetic nephropathy. Diabetes Metab Res Rev. 2015;31(7):699–706.CrossRefPubMed Wang G, Lai FM, Chow KM, Kwan BC, Pang WF, Luk CC, Leung CB, Li PK, Szeto CC. Urinary mRNA levels of ELR-negative CXC chemokine ligand and extracellular matrix in diabetic nephropathy. Diabetes Metab Res Rev. 2015;31(7):699–706.CrossRefPubMed
16.
go back to reference Jiang A, Song A, Zhang C. Modes of podocyte death in diabetic kidney disease: an update. J Nephrol. 2022;35(6):1571–84.CrossRefPubMed Jiang A, Song A, Zhang C. Modes of podocyte death in diabetic kidney disease: an update. J Nephrol. 2022;35(6):1571–84.CrossRefPubMed
17.
go back to reference Fukuda A, Minakawa A, Kikuchi M, Sato Y, Nagatomo M, Nakamura S, Mizoguchi T, Fukunaga N, Shibata H, Naik AS, Wiggins RC, Fujimoto S. Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy. Sci Rep. 2020;10(1):18209.CrossRefPubMedPubMedCentral Fukuda A, Minakawa A, Kikuchi M, Sato Y, Nagatomo M, Nakamura S, Mizoguchi T, Fukunaga N, Shibata H, Naik AS, Wiggins RC, Fujimoto S. Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy. Sci Rep. 2020;10(1):18209.CrossRefPubMedPubMedCentral
18.
go back to reference Rojek A, Füchtbauer EM, Kwon TH, Frøkiaer J, Nielsen S. Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice. Proc Natl Acad Sci U S A. 2006;103(15):6037–42.CrossRefPubMedPubMedCentral Rojek A, Füchtbauer EM, Kwon TH, Frøkiaer J, Nielsen S. Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice. Proc Natl Acad Sci U S A. 2006;103(15):6037–42.CrossRefPubMedPubMedCentral
19.
go back to reference Zhou L, Liu G, Jia Z, Yang KT, Sun Y, Kakizoe Y, Liu M, Zhou S, Chen R, Yang B, Yang T. Increased susceptibility of db/db mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters. Am J Physiol Renal Physiol. 2013;305(10):F1491–7.CrossRefPubMedPubMedCentral Zhou L, Liu G, Jia Z, Yang KT, Sun Y, Kakizoe Y, Liu M, Zhou S, Chen R, Yang B, Yang T. Increased susceptibility of db/db mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters. Am J Physiol Renal Physiol. 2013;305(10):F1491–7.CrossRefPubMedPubMedCentral
20.
go back to reference Gao C, Zhang W. Urinary AQP5 is independently associated with eGFR decline in patients with type 2 diabetes and nephropathy. Diabetes Res Clin Pract. 2019;155:107805.CrossRefPubMedPubMedCentral Gao C, Zhang W. Urinary AQP5 is independently associated with eGFR decline in patients with type 2 diabetes and nephropathy. Diabetes Res Clin Pract. 2019;155:107805.CrossRefPubMedPubMedCentral
Metadata
Title
Urinary podocyte stress marker as a prognostic indicator for diabetic kidney disease
Authors
Lingfeng Zeng
Jack Kit-Chung Ng
Winston Wing-Shing Fung
Gordon Chun-Kau Chan
Kai-Ming Chow
Cheuk-Chun Szeto
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2024
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-024-03471-8

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