scholarly journals The Spectrum of Children's Kidney Diseases—2403 Renal Biopsy-Proven Cases from a Single Centre in China Between 1999 and 2019

2021 ◽  
Author(s):  
Li-Jun Jiang ◽  
Zan-Hua Rong ◽  
Xue Zhao ◽  
Zhi-Yan Dou ◽  
Lin Yang
Keyword(s):  
Kidney Disease ◽  
Alport Syndrome ◽  
Kidney Diseases ◽  
Membranous Glomerulonephritis ◽  
Glomerular Disease ◽  
Proliferative Glomerulonephritis ◽  
Glomerular Diseases ◽  
Common Cause ◽  
Thin Basement Membrane Nephropathy ◽  
Renal Biopsies

Abstract Background: This study aimed to investigate the clinical and pathological characteristics and the changes in glomerular diseases in 2403 pediatric renal biopsies from 1999 to 2019.Methods: Renal biopsies performed on children aged ≤18 years between 1999 and 2019 were analysed at our center. We analysed the clinical and histological characteristics, distribution of pediatric glomerular diseases with various clinical presentations, and changes in the glomerular disease patterns during the study period.Results: The most common primary glomerular disease was IgA nephropathy (IgAN) (24.3%), followed by minimal change disease (MCD) (15.3%) and membranous glomerulonephritis (MN) (13.1%). Henoch-Schonlein purpura nephritis (HSPN) (18.1%) and lupus nephritis (LN) (7.2%) were the most frequently recorded secondary glomerular diseases. Alport syndrome and thin basement membrane nephropathy (TBMN) were the most common inherited glomerular diseases, accounting for 1.2% and 0.6% of the total glomerular diseases in children, respectively. The number of boys with IgAN, MCD and IgM nephropathy (IgMN) was higher than that of girls, while the number of girls with MN and LN was higher than that of boys. The frequencies of MCD, MN, IgMN and endocapillary proliferative glomerulonephritis (EnPGN) in the 13-18-year-old group were higher than those in the 0-12-year-old group, while the frequencies of IgAN, mesangial proliferative glomerulonephritis (MsPGN) and focal proliferative glomerulonephritis (FPGN) were lower than those in the 0-12-year-old group. The ratio of Alport syndrome and TBMN in the 0-12-year-old group was higher than that in the 13-18-year-old group. The proportion of patients with MCD and MN in 2010-2019 was higher than that in 1999-2009, while the ratio of IgAN, MsPGN, IgMN, EnPGN, membranoproliferative glomerulonephritis (MPGN), HSPN and HBV-associated glomerulonephritis (HBV-GN) decreased. MCD (28.5%) was the most common cause of nephrotic syndrome (NS). In children with haematuria and proteinuria, HSPN (38.8%) and IgAN (36.9%) were more common than other glomerular diseases. IgAN (39.4%) was the most common cause of AKI. Sclerosing glomerulonephritis (SGN) (21.1%) was the main cause of progressive chronic kidney disease (CKD).Conclusions: Glomerular diseases in children were related to sex and age. From 1999 to 2019, the spectrum of children's kidney disease in our center changed significantly.

scholarly journals The Spectrum of Children's Kidney Diseases—2403 Renal Biopsy-proven Cases from a Single Centre in China between 1999 and 2019

2021 ◽  
Author(s):  
Li-Jun Jiang ◽  
Xue Zhao ◽  
Zhi-Yan Dou ◽  
Zan-Hua Rong ◽  
Lin Yang
Keyword(s):  
Kidney Disease ◽  
Alport Syndrome ◽  
Kidney Diseases ◽  
Membranous Glomerulonephritis ◽  
Proliferative Glomerulonephritis ◽  
Renal Diseases ◽  
Glomerular Diseases ◽  
Common Cause ◽  
Thin Basement Membrane Nephropathy ◽  
Renal Biopsies

Abstract Background: This study aimed to investigate the clinical and pathological characteristics and the profile of and temporal changes in glomerular diseases in 2403 paediatric renal biopsies from 1999 to 2019.Methods: Renal biopsies performed on children aged ≤18 years between 1999 and 2019 were analysed at our centre. We analysed the clinical and histological characteristics, distribution of paediatric renal diseases with various clinical presentations, and changes in the pattern of kidney disease during the study period.Results: The most common primary glomerular disease was IgA nephropathy (IgAN) (24.3%), followed by minimal change disease (MCD) (15.3%) and membranous glomerulonephritis (MN) (13.1%). Henoch-Schonlein purpura nephritis (HSPN) (18.1%) and lupus nephritis (LN) (7.2%) were the most frequently recorded secondary glomerular diseases. Alport syndrome and thin basement membrane nephropathy (TBMN) were the most common inherited glomerular diseases, accounting for 1.2% and 0.6% of the total glomerular diseases in children, respectively. The number of boys with IgAN, MCD and IgM nephropathy (IgMN) was significantly higher than that of girls, while the number of girls with MN and LN was significantly higher than that of boys. The frequencies of MCD, MN, IgMN and endocapillary proliferative glomerulonephritis (EnPGN) in the 13-18-year-old group were significantly higher than those in the 0-12-year-old group, while the frequencies of IgAN, mesangial proliferative glomerulonephritis (MsPGN) and focal proliferative glomerulonephritis (FPGN) were lower than those in the 0-12-year-old group. The ratio of Alport syndrome and TBMN in the 0-12-year-old group was significantly higher than that in the 13-18-year-old group. The proportion of patients with MCD and MN in 2010-2019 was significantly higher than that in 1999-2009, while the ratio of IgAN, MsPGN, IgMN, EnPGN, membranoproliferative glomerulonephritis (MPGN), HSPN and HBV-associated glomerulonephritis (HBV-GN) decreased. MCD (28.5%) was the most common cause of nephrotic syndrome (NS). In children with haematuria and proteinuria, HSPN (38.8%) and IgAN (36.9%) were more common than other glomerular diseases. IgAN (39.4%) was the most common cause of AKI. Sclerosing glomerulonephritis (SGN) (21.1%) was the main cause of progressive chronic kidney disease (CKD).Conclusions: Glomerular diseases in children were related to sex and age. From 1999 to 2019, the spectrum of children's kidney disease in our centre changed significantly.

scholarly journals CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Protective Role ◽  
Control Group ◽  
Podocyte Injury ◽  
Ccr2 Expression ◽  
Cd73 Expression

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

MO046NGS PANEL PERFORMANCE IN THE DIAGNOSIS OF HEREDITARY RENAL DISEASE IN SOUTHERN SPAIN

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
María del Mar Del Águila García ◽  
Antonio M Poyatos Andújar ◽  
Ana Isabel Morales García ◽  
Margarita Martínez Atienza ◽  
Susana García Linares ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Polycystic Kidney Disease ◽  
Genetic Study ◽  
Alport Syndrome ◽  
Autosomal Dominant ◽  
Kidney Diseases ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Hereditary Renal Disease

Abstract Background and Aims Hereditary renal disease (HRD) is still underdiagnosed: although we know aspects related to autosomal dominant polycystic kidney disease (ADPKD), we know little about the incidence and prevalence of other entities such as Alport syndrome. Altogether, HRD can represent 15% of individuals undergoing renal replacement therapy (RRT) or could even be higher. The advancement of genetics at the healthcare level let to achieve accurate and early renal diagnoses, as well as the incorporation of genetic counseling to families, all of which will result in better management of the disease in its initial stages and the possibility of offering reproductive options that avoid transmission to offspring. Our objective is to know the performance offered by the implementation of the ERH panel through Next Generation Sequencing (NGS) in our healthcare area. Method Observational-descriptive study of 259 probands (141 men / 118 women), mean age of 46 years (30 pediatric / 123 over 50 years), with chronic kidney disease and suspected hereditary cause attended in the specialized consultation of our centers from October 2018 to October 2020. The DNA extracted from leukocytes obtained by venipuncture was processed with Nephropathies Solution version 3 panel (SOPHiA Genetics) according to the manufacturer's protocol. This panel covers the coding regions and splicing junctions of 44 HRD-related genes such as nephrotic syndromes, polycystic kidney diseases, Bartter syndromes, Alport syndrome, CAKUT or tubulopathies (table 1). The sequencing of the libraries was done in a MiSeq (Illumina Inc), the bioinformatic analysis of the data and annotation of variants was performed using the SOPHiA DDM 5.8.0.3 software, and the revision of variants by consulting the main databases (ClinVar, Exac, HGMD, NCBI, PKD Foundation, LOVD). Results The panel was informative (pathogenic or probably pathogenic) in 80/259 patients (31%) and 56/259 cases (21.66%) of variants of uncertain significance (VSI) were detected. Autosomal dominant polycystic kidney disease accounted for 76.2% of the variants identified (56.2% PKD1, 20% PKD2), following Alport syndrome with 15% and the alterations in the PKHD1 gene associated with renal polycystic disease in its recessive form with about 4% (Figure 1). We have also identified a case of autosomal dominant tubulointerstitial kidney disease associated with the UMOD gene that was not suspected until the genetic study was performed. We highlight that 45% (36/80) of the variants identified as responsible for the renal disease are not yet described. Overall, the most prevalent type of mutation is that which produces displacement in the reading frame or frameshift (Figure 2). Individually, frameshift is the most frequent alteration in PKD1, PKD2 and COL4A5, while for PKHD1, COL4A3 and COL4A4 it is missense. Conclusion Our NGS HRD panel a) offers an adequate diagnostic performance at the healthcare level, with definitive results in 1 out of 3 cases and has also allowed the performance of many carrier studies among family members b) is able of diagnosing the most frequent disease, ADPKD and Alport syndrome, as well as unresolved or poorly characterized cases, and c) opens the horizon for new diagnoses, all without increasing costs by outsourcing services. All this makes the genetic study of renal pathology a useful and efficient strategy. These results encourage us to enhance the resources in this area that we consider to be of strategic value.

FC 012PRIMARY KIDNEY DISEASE IMPACTS OUTCOME IN CKD PREGNANCIES: COMPLICATIONS IN COL4A3-5 RELATED DISEASE (ALPORT SYNDROME) VS OTHER CKD PREGNANCIES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Rozemarijn Snoek ◽  
Margriet Gosselink ◽  
Liffert Vogt ◽  
Margriet De Jong ◽  
Agne Cerkauskaite ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Pregnancy Outcomes ◽  
Alport Syndrome ◽  
Low Birthweight ◽  
Kidney Diseases ◽  
Related Disease ◽  
Ckd Stage ◽  
Before And After ◽  
Stage 1 ◽  
Italian Cohort

Abstract Background and Aims Chronic kidney disease (CKD) affects approximately 3% of pregnant women. CKD increases the risk of pregnancy complications such as prematurity, low birthweight and pre-eclampsia. Also, kidney function can deteriorate more quickly due to pregnancy. There is limited knowledge on pregnancy outcomes in specific kidney diseases. The aim of the ALPART network is to study pregnancy outcomes differentiated by CKD aetiology. We have started with COLA3-5 related disease (Alport syndrome), which is one of the most prevalent monogenic kidney diseases. Comparing outcomes in COLA3-5 related disease to pregnancies with other CKD aetiologies allows us to investigate whether this specific diagnosis impacts outcome in CKD pregnancies. Method The ALPART network is an international 15-center network, which aims to include ∼200 COLA3-5 related disease pregnancies. In this intermediary analysis, we present data on 109 pregnancies from 68 women with COLA3-5 related disease. We compared outcomes to a cohort of 457 CKD stage 1-2 patients (a similar CKD stage as our cohort) of diverse aetiology from a 2015 Italian study and 159,924 women from the general Dutch population. Results The main pregnancy and kidney outcomes are presented in Figure 1. Foetal outcomes were better in COLA3-5 pregnancies than in pregnancies of women with CKD stage 1-2 of diverse aetiology. We saw less prematurity (17% vs 36% respectively) and a higher mean birthweight of 3216 ± 663 gram compared to 2768 ± 680 in the Italian cohort. Maternal kidney outcomes should be interpreted with caution (&gt;30% missing data): proteinuria (73%) and hypertension (30%) were more frequent in COLA3-5 pregnancies than the Italian cohort. In the ALPART cohort, 10% developed severe hypertension. Median eGFR was not impacted by pregnancy and decline of eGFR before and after pregnancy were not significantly different between groups. Conclusion Fetal outcomes in pregnancies with COLA3-5 related disease seem to be more favorable than in a cohort with mixed cause of CKD. In this intermediary analysis, proteinuria levels and frequency of new-onset hypertension in pregnancy are higher. There is no significant eGFR loss during pregnancy or increased eGFR deterioration in the long-term. The differences between COLA3-5 and general CKD pregnancies underscore the importance of investigating pregnancy outcomes in specific kidney disease phenotypes to ensure adequate (pre-) pregnancy counselling and care.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes

2018 ◽  
Vol 154 (1) ◽  
pp. 30-36
Author(s):  
Ang Li ◽  
Er-Zhi Gao ◽  
Ying-Xia Cui ◽  
Jian-Hong Liu ◽  
Xing Lv ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Collagen Type ◽  
Kidney Diseases ◽  
Collagen Type Iv ◽  
Bioinformatics Analyses ◽  
Thin Basement Membrane Nephropathy ◽  
Disease Phenotypes ◽  
Type Iv ◽  
Novel Variants ◽  
Pedigree Verification

Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, and FSGS. Using bioinformatics analyses and pedigree verification, we show that these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS. Furthermore, we found that the collagen type IV-associated kidney disease phenotypes are heterogeneous, with overlapping pathology and genetic mutations. We propose that COL4A4-associated TBMN, ADAS, and FSGS should be considered as collagen type IV kidney disease subtypes that represent different phases of disease progression.

scholarly journals Management of Canadian Pediatric Patients With Glomerular Diseases During the COVID-19 Pandemic: Recommendations From the Canadian Association of Pediatric Nephrologists COVID-19 Rapid Response Team

2020 ◽  
Vol 7 ◽  
pp. 205435812097071
Author(s):  
Cal Robinson ◽  
Michelle Ruhl ◽  
Amrit Kirpalani ◽  
Abdullah Alabbas ◽  
Damien Noone ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Peer Review ◽  
Care Delivery ◽  
Rapid Response Team ◽  
Glomerular Disease ◽  
Rapid Response ◽  
Optimal Care ◽  
Glomerular Diseases ◽  
Canadian Association ◽  
Response Team

Purpose: The goal of these recommendations is to provide guidance on the optimal care of children with glomerular diseases during the COVID-19 pandemic. Patients with glomerular diseases are known to be more susceptible to infection. Risk factors include decreased vaccine uptake, urinary loss of immunoglobulins, and treatment with immunosuppressive medications. The Canadian Society of Nephrology (CSN) recently published guidelines on the care of adult glomerulonephritis patients. This guideline aims to expand and adapt those recommendations for programs caring for children with glomerular diseases. Sources of information: We used the CSN COVID-19 Rapid Response Team adult glomerulonephritis recommendations, published in the Canadian Journal of Kidney Health and Disease, as the foundation for our guidelines. We reviewed documents published by nephrology and non-nephrology societies and health care agencies focused on kidney disease and immunocompromised populations. Finally, we conducted a formal literature review of publications relevant to pediatric and adult glomerular disease, chronic kidney disease, hypertension, and immunosuppression in the context of the COVID-19 pandemic. Methods: The leadership of the Canadian Association of Pediatric Nephrologists (CAPN), which is affiliated with the CSN, identified a team of clinicians and researchers with expertise in pediatric glomerular diseases. The aim was to adapt Canadian adult glomerulonephritis guidelines to make them applicable to children and discuss pediatric-specific considerations. The updated guidelines were peer-reviewed by senior clinicians with expertise in the care of childhood glomerular diseases. Key findings: We identified a number of key areas of glomerular disease care likely to be affected by the COVID-19 pandemic, including (1) clinic visit scheduling, (2) visit types, (3) provision of multidisciplinary care, (4) blood work and imaging, (5) home monitoring, (6) immunosuppression, (7) other medications, (8) immunizations, (9) management of children with suspected COVID-19, (10) renal biopsy, (11) patient education and support, and (12) school and child care. Limitations: There are minimal data regarding the characteristics and outcomes of COVID-19 in adult or pediatric glomerular disease patients, as well as the efficacy of strategies to prevent infection transmission within these populations. Therefore, the majority of these recommendations are based on expert opinion and consensus guidance. To expedite the publication of these guidelines, an internal peer-review process was conducted, which may not have been as rigorous as formal journal peer-review. Implications: These guidelines are intended to promote optimal care delivery for children with existing or newly diagnosed glomerular diseases during the COVID-19 pandemic. The implications of modified care delivery, altered immunosuppression strategies, and limited access to existing resources remain uncertain.

scholarly journals Albumin contributes to kidney disease progression in Alport syndrome

2016 ◽  
Vol 311 (1) ◽  
pp. F120-F130 ◽  
Author(s):  
George Jarad ◽  
Russell H. Knutsen ◽  
Robert P. Mecham ◽  
Jeffrey H. Miner
Keyword(s):  
Kidney Disease ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Alport Syndrome ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Serum Triglyceride ◽  
Transforming Growth Factor Β ◽  
Collagen Type Iv ◽  
Albumin Concentration

Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout ( Alb−/−) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb+/− mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout ( Col4a3−/−) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3−/−; Alb−/− mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3−/−; Alb+/+ and Col4a3−/−; Alb+/− mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy.

scholarly journals Use of Lipid-Modifying Agents for the Treatment of Glomerular Diseases

2021 ◽  
Vol 11 (8) ◽  
pp. 820
Author(s):  
Mengyuan Ge ◽  
Sandra Merscher ◽  
Alessia Fornoni
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Recent Progress ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Glomerular Diseases ◽  
Intracellular Lipids ◽  
Lipid Modifying Agents ◽  
Made In

Although dyslipidemia is associated with chronic kidney disease (CKD), it is more common in nephrotic syndrome (NS), and guidelines for the management of hyperlipidemia in NS are largely opinion-based. In addition to the role of circulating lipids, an increasing number of studies suggest that intrarenal lipids contribute to the progression of glomerular diseases, indicating that proteinuric kidney diseases may be a form of “fatty kidney disease” and that reducing intracellular lipids could represent a new therapeutic approach to slow the progression of CKD. In this review, we summarize recent progress made in the utilization of lipid-modifying agents to lower renal parenchymal lipid accumulation and to prevent or reduce kidney injury. The agents mentioned in this review are categorized according to their specific targets, but they may also regulate other lipid-relevant pathways.

scholarly journals Case Report: Preimplantation Genetic Testing and Pregnancy Outcomes in Women With Alport Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei-Hui Shi ◽  
Mu-Jin Ye ◽  
Song-Chang Chen ◽  
Jun-Yu Zhang ◽  
Yi-Yao Chen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Pregnancy Outcomes ◽  
Alport Syndrome ◽  
Kidney Diseases ◽  
High Rate ◽  
Singleton Pregnancy ◽  
Fetal Outcomes ◽  
Preimplantation Genetic Testing ◽  
Monogenic Diseases

BackgroundAlport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in COL4A5 at Xq22 accounts for 80–85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling.MethodsPrenatal diagnoses were performed by amplifying targeted regions of COL4A5. Targeted next-generation sequencing (NGS)-based haplotype analysis or karyomapping was performed in two patients. Pregnancy outcomes in the three patients were collected and analyzed. Published Alport syndrome cases were searched in Pubmed and Embase.ResultsPrenatal diagnoses in two cases showed one fetus harbored the same pathogenic mutation as the proband and the other was healthy. The couple with an affected fetus and the patient with a family history of Alport syndrome chose to take the preimplantation genetic testing (PGT) procedure. One unaffected embryo was transferred to the uterus, and a singleton pregnancy was achieved, respectively. Two patients presented non-nephrotic range proteinuria (&lt;3 g/24 h) during pregnancy and the three cases all delivered at full-term. However, published Alport cases with chronic kidney disease or proteinuria during pregnancy were came with a high rate (75%) of adverse maternal and fetal outcomes.ConclusionThe PGT procedure performed in this study was proven to be practicable and might be expanded to be applied in other monogenic diseases. Moderate or severe renal impairments in Alport syndrome were strongly associated with adverse maternal and fetal outcomes, and baseline proteinuria was a potential predictor for pregnancy outcomes of Alport syndrome as other kidney diseases.

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