WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging

Background/Aims: WNT4 protein is important for kidney development. Its expression was found to be altered in experimental models of chronic kidney disease (CKD). However, the expression of the WNT4 gene has yet not been studied in human renal biopsy samples from patients with broad spectrum of glome...

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Main Authors: Jolanta Kiewisz, Agnieszka Skowronska, Agata Winiarska, Anna Pawlowska, Jacek Kiezun, Anna Rozicka, Agnieszka Perkowska-Ptasinska, Zbigniew Kmiec, Tomasz Stompor
Format: Article
Language:English
Published: Karger Publishers 2019-05-01
Series:Kidney & Blood Pressure Research
Subjects:
Online Access:https://www.karger.com/Article/FullText/498989
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author Jolanta Kiewisz
Agnieszka Skowronska
Agata Winiarska
Anna Pawlowska
Jacek Kiezun
Anna Rozicka
Agnieszka Perkowska-Ptasinska
Zbigniew Kmiec
Tomasz Stompor
author_facet Jolanta Kiewisz
Agnieszka Skowronska
Agata Winiarska
Anna Pawlowska
Jacek Kiezun
Anna Rozicka
Agnieszka Perkowska-Ptasinska
Zbigniew Kmiec
Tomasz Stompor
author_sort Jolanta Kiewisz
collection DOAJ
description Background/Aims: WNT4 protein is important for kidney development. Its expression was found to be altered in experimental models of chronic kidney disease (CKD). However, the expression of the WNT4 gene has yet not been studied in human renal biopsy samples from patients with broad spectrum of glomerular disease and at different stages of CKD. Thus, the aim of the study was to assess the WNT4 gene expression in renal biopsies of 98 patients using the real-time PCR technique. Materials: In order to assess the relative amounts of mRNA, in samples of patients with manifestation of different renal diseases and separately at different stages of CKD, by QPCR, total RNA was isolated from human kidney tissues collected during renal biopsies. Results of blood and urine samples assessment were used to calculate the correlations of biochemical parameters with WNT4 gene expression in both studied groups. Results: After pathomorphological evaluation, 49 patients were selected as presenting the most common cases in the studied group. Among the patients who developed focal segmental glomerulosclerosis (FSGS; n = 13), IgA nephropathy (IgAN; n = 10), IgAN with morphological presentation of focal segmental glomerulosclerosis (IgAN/FSGS; n = 8), membranous nephropathy (MN; n = 12), and lupus nephritis (LN; n = 6) were included in the analysis. We found that the level of WNT4 mRNA was higher in kidney specimens obtained from patients with MN as compared to those diagnosed with LN or IgAN. A correlation between WNT4 gene expression and serum albumin and cholesterol levels was observed in patients with FSGS, while WNT4 mRNA levels correlated with plasma sodium in patients diagnosed with LN. After consideration of 98 patients, based on the KDIGO classification of CKD, 20 patients were classified as CKD1 stage, 23 as stage 2, 13 as stage 3a, 11 as stage 3b, 13 as stage 4, and 18 as stage 5. WNT4 gene expression was lower in the CKD patients in stage 2 as compared to CKD 3a. Correlations of WNT4 mRNA level at different stages of CKD with indices of kidney function and lipid metabolism such as serum levels of HDL and LDL cholesterol, TG, urea, creatinine, sodium, and potassium were also found. Conclusions: Our results suggest that altered WNT4 gene expression in patients with different types of glomerular diseases and patients at different stages of CKD may play a role in kidney tissue disorganization as well as disease development and progression.
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spelling doaj.art-8a921dad048746a3bf3500bf778bfe032022-12-22T00:08:57ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432019-05-0144220021010.1159/000498989498989WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on StagingJolanta KiewiszAgnieszka SkowronskaAgata WiniarskaAnna PawlowskaJacek KiezunAnna RozickaAgnieszka Perkowska-PtasinskaZbigniew KmiecTomasz StomporBackground/Aims: WNT4 protein is important for kidney development. Its expression was found to be altered in experimental models of chronic kidney disease (CKD). However, the expression of the WNT4 gene has yet not been studied in human renal biopsy samples from patients with broad spectrum of glomerular disease and at different stages of CKD. Thus, the aim of the study was to assess the WNT4 gene expression in renal biopsies of 98 patients using the real-time PCR technique. Materials: In order to assess the relative amounts of mRNA, in samples of patients with manifestation of different renal diseases and separately at different stages of CKD, by QPCR, total RNA was isolated from human kidney tissues collected during renal biopsies. Results of blood and urine samples assessment were used to calculate the correlations of biochemical parameters with WNT4 gene expression in both studied groups. Results: After pathomorphological evaluation, 49 patients were selected as presenting the most common cases in the studied group. Among the patients who developed focal segmental glomerulosclerosis (FSGS; n = 13), IgA nephropathy (IgAN; n = 10), IgAN with morphological presentation of focal segmental glomerulosclerosis (IgAN/FSGS; n = 8), membranous nephropathy (MN; n = 12), and lupus nephritis (LN; n = 6) were included in the analysis. We found that the level of WNT4 mRNA was higher in kidney specimens obtained from patients with MN as compared to those diagnosed with LN or IgAN. A correlation between WNT4 gene expression and serum albumin and cholesterol levels was observed in patients with FSGS, while WNT4 mRNA levels correlated with plasma sodium in patients diagnosed with LN. After consideration of 98 patients, based on the KDIGO classification of CKD, 20 patients were classified as CKD1 stage, 23 as stage 2, 13 as stage 3a, 11 as stage 3b, 13 as stage 4, and 18 as stage 5. WNT4 gene expression was lower in the CKD patients in stage 2 as compared to CKD 3a. Correlations of WNT4 mRNA level at different stages of CKD with indices of kidney function and lipid metabolism such as serum levels of HDL and LDL cholesterol, TG, urea, creatinine, sodium, and potassium were also found. Conclusions: Our results suggest that altered WNT4 gene expression in patients with different types of glomerular diseases and patients at different stages of CKD may play a role in kidney tissue disorganization as well as disease development and progression.https://www.karger.com/Article/FullText/498989WNT4Membranous nephropathyLupus nephritisIgA nephropathyFocal/segmental glomerulosclerosis
spellingShingle Jolanta Kiewisz
Agnieszka Skowronska
Agata Winiarska
Anna Pawlowska
Jacek Kiezun
Anna Rozicka
Agnieszka Perkowska-Ptasinska
Zbigniew Kmiec
Tomasz Stompor
WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging
Kidney & Blood Pressure Research
WNT4
Membranous nephropathy
Lupus nephritis
IgA nephropathy
Focal/segmental glomerulosclerosis
title WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging
title_full WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging
title_fullStr WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging
title_full_unstemmed WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging
title_short WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging
title_sort wnt4 expression in primary and secondary kidney diseases dependence on staging
topic WNT4
Membranous nephropathy
Lupus nephritis
IgA nephropathy
Focal/segmental glomerulosclerosis
url https://www.karger.com/Article/FullText/498989
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