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1.
J. bras. nefrol ; 46(3): e20230040, July-Sept. 2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1564718

ABSTRACT

Abstract Introduction: Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a Brazilian sample is sparce. Therefore, the aim of this study was to identify risk factors for renal outcomes and death in a Brazilian cohort of ADPKD patients. Methods: Patients had the first medical appointment between January 2002 and December 2014, and were followed up until December 2019. Associations between clinical and laboratory variables with the primary outcome (sustained decrease of at least 57% in the eGFR from baseline, need for dialysis or renal transplantation) and the secondary outcome (death from any cause) were analyzed using a multiple Cox regression model. Among 80 ADPKD patients, those under 18 years, with glomerular filtration rate <30 mL/min/1.73 m2, and/or those with missing data were excluded. There were 70 patients followed. Results: The factors independently associated with the renal outcomes were total kidney length - adjusted Hazard Ratio (HR) with a 95% confidence interval (95% CI): 1.137 (1.057-1.224), glomerular filtration rate - HR (95% CI): 0.970 (0.949-0.992), and serum uric acid level - HR (95% CI): 1.643 (1.118-2.415). Diabetes mellitus - HR (95% CI): 8.115 (1.985-33.180) and glomerular filtration rate - HR (95% CI): 0.957 (0.919-0.997) were associated with the secondary outcome. Conclusions: These findings corroborate the hypothesis that total kidney length, glomerular filtration rate and serum uric acid level may be important prognostic predictors of ADPKD in a Brazilian cohort, which could help to select patients who require closer follow up.


Resumo Introdução: É importante identificar fatores de risco para progressão da doença renal policística autossômica dominante (DRPAD). Entretanto, são escassos os estudos que avaliam esse assunto utilizando amostra brasileira. Portanto, o objetivo deste estudo foi identificar fatores de risco para desfechos renais e óbito em coorte brasileira de pacientes com DRPAD. Métodos: Os pacientes tiveram o primeiro atendimento médico entre janeiro/2002 e dezembro/2014, sendo acompanhados até dezembro/2019. Associações entre variáveis clínicas e laboratoriais com desfecho primário (redução sustentada de pelo menos 57% na TFGe em relação ao valor basal, necessidade de diálise ou transplante renal) e desfecho secundário (óbito por qualquer causa) foram analisadas pelo modelo de regressão múltipla de Cox. Entre 80 pacientes com DRPAD, foram excluídos aqueles menores de 18 anos, com TFG <30 mL/min/1,73 m2 e/ou aqueles com dados ausentes. Foram acompanhados 70 pacientes. Resultados: Fatores independentemente associados aos desfechos renais foram: comprimento renal total - Razão de Risco (HR) ajustada com intervalo de confiança de 95% (IC 95%): 1,137 (1,057-1,224), taxa de filtração glomerular - HR (IC 95%): 0,970 (0,949-0,992) e nível sérico de ácido úrico - HR (IC 95%): 1,643 (1,118-2,415). Diabetes mellitus - HR (IC 95%): 8,115 (1,985-33,180) e TFG - HR (IC 95%): 0,957 (0,919-0,997) foram associados ao desfecho secundário. Conclusões: Esses achados corroboram a hipótese de que comprimento renal total, TFG e nível sérico de ácido úrico podem ser importantes preditores prognósticos de DRPAD em uma coorte brasileira, o que pode ajudar a selecionar pacientes que necessitam de acompanhamento mais próximo.

2.
The Journal of Practical Medicine ; (24): 1006-1010, 2024.
Article in Chinese | WPRIM | ID: wpr-1020865

ABSTRACT

Objective To investigate the application value of single nucleotide polymorphism(SNP)linkage analysis based on next-generation sequencing(NGS)technology in preimplantation genetic testing(PGT)of families with autosomal recessive polycystic kidney disease(ARPKD).Methods A family with ARPKD was selected,where the female member had a pregnancy ultrasound revealing polycystic kidney in the fetus.Genetic testing showed compound heterozygous mutations of the polycystic kidney/polycystic liver disease 1 gene(PKHD1),c.10444C>T(paternal)and c.4303del(maternal),with the c.4303del mutation being reported for the first time.Targeting the coding region of the PKHD1 gene,335 high-density tightly linked SNP sites were selected in the upstream and downstream 2M regions using multiplex polymerase chain reaction(PCR)and NGS.The couple′s SNP risk haplotypes carrying gene mutations were constructed.After in vitro fertilization,blastocyst culture was performed.Trophoblastic cells obtained from the biopsy were subjected to whole-genome amplification,and NGS was used for linkage analysis and low-depth chromosomal aneuploidy screening of the embryos.Sanger sequencing was used to verify the results of embryo linkage analysis.Results Among the 6 biopsied embryos,4 were mutation-free and euploid,1 exhibited heterozygous for the mutation and mosaic while another unstable sequencing data,making it impossible to judge.One of the mutation-free and developmentally healthy euploid embryos was implanted into the maternal uterus,resulting in the full-term delivery of a healthy baby.Conclusion Application of NGS-based SNP linkage analysis in PGT can effectively blocking the vertical transmission of ARPKD within families,while avoiding abortion issues caused by aneuploid embryos.This study is also the first PGT report target-ing the PKHD1 gene c.4303del mutation.

3.
Autops. Case Rep ; 14: e2024498, 2024. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1564016

ABSTRACT

ABSTRACT Localized cystic kidney disease (LCKD) is a distinct renal disorder characterized by the presence of cysts within specific regions of the kidneys. We present a rare case of a 41-year-old African American man, who presented to our medical center with lower urinary tract symptoms and gross hematuria. The initial assessment culminated in the identification of an uncomplicated urinary tract infection, prompting the prescription of appropriate oral antibiotic therapy. On follow-up after 5 months, the patient presented with gross hematuria. Imaging studies revealed a mixed-density cystic lesion of 2.6 cm situated within the interpolar region of the right kidney. This cystic lesion exhibited intricate septations at the superior pole of the kidney. Robotic-assisted right partial nephrectomy was performed, and pathologic examination was diagnostic for LCKD. This report not only underscores the uniqueness of LCKD but also presents a comprehensive review of the existing literature that pertains to this condition. Particular emphasis is placed upon its inherent benign behavior and its marked divergence from the progressive trajectory commonly associated with other renal diseases. We also explored the incidental findings of the disease, its diverse clinical symptomatology, conceivable etiological underpinnings, and the array of diagnostic modalities used. Finally, similarities in histopathologic findings with polycystic kidney disease and other entities are discussed, underscoring the importance of accurate diagnosis and management.

4.
Rev. cuba. med ; 62(2)jun. 2023.
Article in Spanish | LILACS, CUMED | ID: biblio-1530128

ABSTRACT

La enfermedad poliquística renal autosómica dominante es considerada la enfermedad renal genética más frecuente y es la cuarta causa de enfermedad renal crónica a nivel mundial. Afecta a cerca de 1 por cada 1000 nacidos vivos. La enfermedad poliquística hepática es la manifestación extrarrenal más frecuente de la enfermedad poliquística renal. La cirrosis hepática constituye un hallazgo tardío en esta enfermedad y su presentación es más común en el anciano, y la descompensación de la enfermedad con insuficiencia hepática como causa de muerte. Presentamos el caso de un paciente masculino de 60 años con antecedentes patológicos personales de la enfermedad poliquística renal con ascitis a tensión, y edemas en ambos miembros inferiores con datos de insuficiencia hepática y evolución desfavorable hasta su fallecimiento. Aunque la presencia de la falla hepática se asocia a un pronóstico precario, la detección precoz puede suponer el inicio de un tratamiento oportuno y apropiado que puede ser beneficioso(AU)


Autosomal dominant polycystic kidney disease is considered the most common genetic kidney disease and the fourth leading cause of chronic kidney disease worldwide. It affects about 1 in 1,000 live births. Polycystic liver disease is the most common extrarenal manifestation of polycystic kidney disease. Liver cirrhosis is a late finding in this disease and its presentation is more common in the elderly. Decompensation of the disease, with liver failure as the cause of death, is rare in polycystic liver disease. We report the case of a 60-year-old male patient with a personal pathological history of polycystic kidney disease with tense ascites and edema in both lower limbs, with evidence of liver failure and unfavorable evolution until his death. Although the presence of liver failure is associated with poor prognosis, its early detection may mean the initiation of timely and appropriate treatment that may be beneficial(AU)


Subject(s)
Humans , Male , Female , Polycystic Kidney, Autosomal Recessive/diagnostic imaging , Hepatic Insufficiency/epidemiology
5.
J. bras. nefrol ; 45(1): 111-115, Jan.-Mar. 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1430641

ABSTRACT

Abstract Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are conditions related to renal failure that can rarely occur in association as a contiguous gene syndrome. Angiomyolipomas (AMLs) are renal tumors strongly related to TSC that may rupture and cause life-threatening bleedings. We present a patient with TSC, ADPKD, and renal AMLs with persistent hematuria requiring blood transfusion. The persistent hematuria was successfully treated through endovascular embolization, a minimally invasive nephron sparing technique.


Resumo O complexo de esclerose tuberosa (CET) e a doença renal policística autossômica dominante (DRPAD) são condições relacionadas à insuficiência renal que raramente podem ocorrer em associação como uma síndrome do gene contíguo. Angiomiolipomas (AMLs) são tumores renais fortemente relacionados ao CET que podem romper-se e causar hemorragias com risco de vida. Apresentamos um paciente com CET, DRPAD e AMLs renais com hematúria persistente que requer transfusão sanguínea. A hematúria persistente foi tratada com sucesso por meio de embolização endovascular, uma técnica de preservação do néfron minimamente invasiva.

6.
Organ Transplantation ; (6): 24-2023.
Article in Chinese | WPRIM | ID: wpr-959016

ABSTRACT

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and one of the most common causes for end-stage renal disease (ESRD). Kidney transplantation is the optimal renal replacement therapy for ADPKD patients complicated with ESRD. Currently, scholars at home and abroad have a certain controversy about whether polycystic kidney resection is necessary in ADPKD patients before kidney transplantation, and the criteria and methods for polycystic nephrectomy also differ. To further standardize the clinical technical operation of kidney transplantation in ADPKD patients, experts in organ transplantation organized by Branch of Organ Transplantation of Chinese Medical Association formulated this specification from the aspects of diagnosis of ADPKD, indications and contraindications of kidney transplantation for ADPKD, preoperative evaluation and treatment, polycystic nephrectomy, and postoperative management, etc.

7.
Chinese Journal of Nephrology ; (12): 224-228, 2023.
Article in Chinese | WPRIM | ID: wpr-994970

ABSTRACT

The Hippo signaling pathway is highly conserved in evolution, and participates in the regulation of cell proliferation, differentiation, and tissular dynamic balance, and plays an important role in regulating tissue, organ size, and cell number. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage renal disease. Emerging studies have identified the Hippo signaling pathway is closely related to the occurrence and development of ADPKD. The abnormal activity and expression of the main members of the pathway affect the cilia and cell polarity of renal tubular epithelial cells and induce the formation of renal cysts. The review summarizes the potential mechanism of the Hippo pathway in the pathogenesis of ADPKD, the crosstalk with other signaling pathways, and the variances in different species, and discusses the strategies for the treatment of ADPKD based on the Hippo signaling pathway to provide new strategies for the treatment.

8.
Chinese Journal of Nephrology ; (12): 538-541, 2023.
Article in Chinese | WPRIM | ID: wpr-995014

ABSTRACT

Bardet-Biedl syndrome (BBS) is an autosomal recessive hereditary rare disease with high heterogeneity in clinical phenotypes, which can affect multiple systems, such as six fingers/digits deformity, mental impairment, retinopathy, polycystic kidney, etc, and is easily diagnosed according to a single system disease, resulting in misdiagnosis. The paper reports a case of BBS, diagnosed with "renal cyst, developmental delay, chondrosis, and left foot hexadactylism" at 5 years old, "anemia, renal insufficiency, distal renal tubule poisoning, renal osteodystrophy" at 7 years old. At 10 years old, the patient received hemodialysis treatment for uremia. Cloudy vision appeared in both eyes at 14 years old. Because of the prominent manifestation of kidney damage, the patient was misdiagnosed as "polycystic kidney" for a long time, and other systemic damages were ignored. The result of gene sequencing showed that chromosome 16 NM_031885.5 exon17 had one homozygous nonsense mutation. Therefore, the patient was accurately diagnosed as BBS. This paper is the first report of BBS in Li nationality in China. The relevant literature of BBS were reviewed to strengthen clinicians' understanding of the disease and improve patients' prognosis.

9.
Chinese Journal of Nephrology ; (12): 697-704, 2023.
Article in Chinese | WPRIM | ID: wpr-1029225

ABSTRACT

Objective:To establish a conditional knockout mouse model of polycystic kidney disease 1 ( Pkd1) gene based on CRISPR/Cas9 and Cre-loxP gene editing technology, and to provide an animal model for in-depth research on the role of Pkd1 gene in the development of polycystic kidney disease. Methods:In-Fusion technology was used to construct a targeting vector. Corresponding gRNAs, Cas9 mRNAs, and donor vectors carrying the loxP site were prepared based on the Pkd1 gene, and injected into the fertilized eggs of C57BL/6N mice. The fertilized eggs were transferred to the fallopian tubes of female mice with pseudopregnancy. After the newborn mice were identified by PCR and sequencing analysis, Pkd1 flox/flox F0 generation positive mice were selected. The F0 generation positive mice were bred with wild-type mice, and F1 generation heterozygous mice with Pkd1 flox/+ genotype were selected for offspring. F2 generation homozygous mice with Pkd1 flox/flox genotype were obtained through internal expansion, and then hybridized with Cre positive Ggt1/ Cre mice. F3 generation mice with Pkd1 flox/+Ggt1 Cre genotype were obtained. F4 generation mice with Pkd1 flox/flox Ggt1 Cre genotype were obtained by self crossing or backcrossing with F2 generation Pkd1 flox/flox, namely kidney-specific Pkd1 gene knockout mice ( Ggt1-cKO mice). PCR method was used to identify the genotype of mice, and then the mice were divided into wild-type control (WT) group ( n=6), Pkd1 homozygous control (PKD) group ( n=6), and Ggt1-cKO knockout validation (CKO) group ( n=6) according to the gene identification results. Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of Pkd1 mRNA in the kidneys and other organs of mice in each group. HE staining was used to detect the pathological changes in renal tissues of mice in each group. The automatic biochemical detector was used to detect the blood urea nitrogen and serum creatinine levels of mice, and the kidney coefficient was calculated. Results:The PCR detection results showed that the genotype of offspring mice in CKO group was consistent with Pkd1floxflox Ggt1 Cre. Pkd1 gene was only specifically expressed in the kidney, but not in other tissues. The RT-qPCR results showed that the relative expression of Pkd1 mRNA in the renal medulla of CKO group was significantly lower than that of WT and PKD groups. The kidney volume of the CKO group had increased by about twice compared to the WT group. Under the microscope, it could be observed that there were multiple vacuoles of varying sizes and shapes in the kidneys of the CKO group, and there was a significant increase in the interstitial space of the medullary tissue. The kidney coefficient, blood urea nitrogen, and serum creatinine in the CKO group were significantly higher than those in the WT and PKD groups (all P<0.05). Conclusion:Based on CRISPR/Cas9 and Cre-loxP gene editing technology, Pkd1 gene kidney conditional knockout mice can be successfully constructed, providing an animal model for further studying the action mechanism of Pkd1 gene in polycystic kidney disease.

10.
Chinese Journal of Nephrology ; (12): 903-911, 2023.
Article in Chinese | WPRIM | ID: wpr-1029254

ABSTRACT

Objective:To detect and analyze the gene variation types of 64 unrelated pedigrees affected with autosomal dominant polycystic kidney disease (ADPKD), and explore the detection efficiency of multiple gene analysis techniques and variation characteristics.Methods:It was a cross-sectional study. The clinical data of 64 pedigrees with ADPKD from Nephrology Department or Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from December 2017 to August 2020 were retrospectively analyzed. The blood samples of probands and other family members were collected. Genetic analysis was carried out by next generation sequencing, and suspected mutations were verified by multiplex ligation-dependent probe amplification, or long-range PCR combined with Sanger sequencing. Prenatal diagnosis for high-risk fetuses was performed by fetal villi or amniotic fluid cells after genotyping without maternal genomic DNA contamination.Results:Among detected 64 pedigrees, 57 pedigrees (89.06%) had genetic variants in PKD1/PKD2. A total of 49 pathogenic/likely pathogenic variants in PKD1/PKD2 were identified in 51 pedigrees (79.69%), including 14 nonsense variants (28.57%), 14 frameshift variants (28.57%), 11 missense variants (22.45%), 5 splicing variants (10.20%) and 5 deletion variants (10.20%). Of these variants, 87.76% (43/49) were in PKD1 and 12.24% (6/49) were in PKD2. Totally, 14 novel variants in PKD1/ PKD2 were identified, including 7 frameshift variants, 3 splicing variants, 2 nonsense variants, 1 deletion variant and 1 missense variant, of which 11 variants were in PKD1 and 3 variants were in PKD2. Twenty high-risk fetuses from 17 pedigrees received prenatal diagnosis, in whom 6 fetuses had PKD1 variation, and other 14 fetuses had no PKD1/ PKD2-genetic variation. Conclusions:The combination of next-generation sequencing, multiplex ligation-dependent probe amplification, and long-range PCR combined with Sanger sequencing can be helpful for rapid, efficient and accurate genetic diagnosis of ADPKD pedigrees. Point mutations are the most common types in PKD1/PKD2. Fourteen novel variants in PKD1/PKD2 extend its pathogenic variant spectrum and can provide basis for genetic counseling and prenatal diagnosis of ADPKD pedigrees.

11.
Article in Chinese | WPRIM | ID: wpr-1029322

ABSTRACT

This paper reported a woman with polycystic kidney disease who had increased fetal nuchal translucency (NT) in her two sequential pregnancies. The fetal NT thickness in the first pregnancy was 5.1 mm at 12 +5 weeks of gestation, and the infant was born prematurely at 32 gestational weeks. However, the baby girl died due to respiratory insufficiency and severe asphyxia. The NT thickness in the present pregnancy was 5.7 mm at 12 weeks of gestation. Whole-exome sequencing (WES) and Sanger sequencing confirmed that the dead infant and the current fetus carried compound heterozygous variants of maternal c.4255_4256del and paternal c.18366+2T>C in NEB gene, both were pathogenic variants. The current fetus was diagnosed with arthrogryposis multiplex congenita 6 (AMC6). After genetic counseling, the pregnant woman chose to terminate the pregnancy. The pregnant woman was diagnosed as having polycystic kidney disease type 1 caused by large deletions in exons 25-43 of PKD1 gene by WES combined with multiplex ligation-dependent probe amplification technology.

12.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 69(11): e20230334, 2023. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1521483

ABSTRACT

SUMMARY OBJECTIVE: Autosomal dominant polycystic kidney disease is an inherited kidney disorder with mutations in polycystin-1 or polycystin-2. Autosomal recessive polycystic kidney disease is a severe form of polycystic kidney disease that is characterized by enlarged kidneys and congenital hepatic fibrosis. Mutations at PKHD1 are responsible for all typical forms of autosomal recessive polycystic kidney disease. METHODS: We evaluated the children diagnosed with polycystic kidney disease between October 2020 and May 2022. The diagnosis was established by family history, ultrasound findings, and/or genetic analysis. The demographic, clinical, and laboratory findings were evaluated retrospectively. RESULTS: There were 28 children (male/female: 11:17) evaluated in this study. Genetic analysis was performed in all patients (polycystin-1 variants in 13, polycystin-2 variants in 7, and no variants in 8 patients). A total of 18 variants in polycystin-1 and polycystin-2 were identified and 9 (50%) of them were not reported before. A total of eight novel variants were identified as definite pathogenic or likely pathogenic mutations. There was no variant detected in the PKDH1 gene. CONCLUSION: Our results highlighted molecular features of Turkish children with polycystic kidney disease and demonstrated novel variations that can be utilized in clinical diagnosis and prognosis.

13.
Einstein (Säo Paulo) ; 21: eRC0282, 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1440071

ABSTRACT

ABSTRACT Polycystic liver disease, a hereditary pathology, usually manifests as autosomal dominant polycystic kidney disease. The many cysts in the liver cause massive hepatomegaly, majorly affecting the patient's quality of life. In cases of refractory symptoms, liver transplantation is the only treatment choice. A 43-year-old woman was followed up as a hepatology outpatient in August 2020, with a progressive increase in abdominal volume, lower limb edema, and cachexia. The patient was diagnosed with polycystic renal and liver disease with massive hepatomegaly in March 2021, a combined kidney-liver transplant. Liver size represented 13% of the patient's corporal composition, weighing 8.6kg. The patient was discharged on the 7th postoperative day with no complications. Only 10-20% of patients with polycystic liver disease have clinical manifestations, most of which result from hepatomegaly. An increase in liver volume deteriorates liver function until the condition becomes end-stage liver disease, as kidney function is already compromised; liver-kidney transplantation remains the only treatment choice. The case described drew significant attention to the massive hepatomegaly presented in the patient, with the liver representing over 10% of the patient's body weight, approximately five to six times larger than a normal-sized liver.

14.
Rev. méd. Urug ; 38(3): e38312, sept. 2022.
Article in Spanish | LILACS, BNUY | ID: biblio-1409858

ABSTRACT

Resumen: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente. Se caracteriza por la progresiva aparición de quistes renales que suelen conducir a la enfermedad renal crónica extrema en la edad adulta. La aprobación del uso de tolvaptán (antagonista del receptor V2 de la vasopresina) ha marcado un cambio significativo en el tratamiento de esta enfermedad. En los últimos años apareció evidencia que demuestra el beneficio en iniciar tratamiento con tolvaptán en pacientes que presentan una enfermedad con rápida evolución. Se realiza una revisión descriptiva de los principales estudios clínicos publicados en el periodo 2012-2022 y se sugiere un esquema de utilidad para seleccionar aquellos pacientes que pueden beneficiarse del inicio de tratamiento.


Abstract: Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. It is characterized by the progressive appearance of renal cysts that usually lead to extreme chronic kidney disease in adulthood. The approval of the use of tolvaptán (V2 vasopressin receptor antagonist) has meant a significant change in the treatment of this disease. In recent years, evidence has proved the benefits of initiating treatment with tolvaptán in patients with a rapidly evolving disease. A descriptive review of the main clinical studies published in 2012-2022 period is carried out and a useful scheme is suggested to select those patients who can benefit from the start of treatment.


Resumo: A doença renal policística autossômica dominante é a doença renal hereditária mais comum. Caracteriza-se pelo aparecimento progressivo de cistos renais que geralmente levam à doença renal crônica extrema na idade adulta. A aprovação do uso do tolvaptano (antagonista do receptor de vasopressina V2) marcou uma mudança significativa no tratamento dessa doença. Nos últimos anos, surgiram evidências que demonstram o benefício de iniciar o tratamento com tolvaptano em pacientes com doença de evolução rápida. Faz-se uma revisão descritiva dos principais estudos clínicos publicados no período 2012-2022 e sugere-se um esquema útil para selecionar aqueles pacientes que podem se beneficiar do início do tratamento.


Subject(s)
Humans , Polycystic Kidney, Autosomal Dominant/drug therapy , Antidiuretic Hormone Receptor Antagonists/therapeutic use , Tolvaptan/therapeutic use , Randomized Controlled Trials as Topic , Patient Selection
15.
J. bras. nefrol ; 44(2): 224-231, June 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1386027

ABSTRACT

Abstract Introduction: Endothelial nitric oxide synthase (eNOS) genes have been implicated in renal hemodynamics as potent regulators of vascular tone and blood pressure. It has been linked to a reduction in plasma nitric oxide levels. Several studies have recently been conducted to investigate the role of NOS3 gene polymorphisms and end-stage renal disease (ESRD). However, the results are still unclear and the mechanisms are not fully defined. As a result, we conducted a meta-analysis to examine the relationship between NOS3 gene polymorphism and ESRD in autosomal polycystic kidney disease (ADPKD) patients. Methods: To assess the relationship between NOS3 gene polymorphism and ESRD, relevant studies published between September 2002 and December 2020 were retrieved from the PubMed (Medline), EMBASE, Google Scholar, and Web of Science databases. The pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using a fixed-effect model. To assess the heterogeneity of studies, we used Cochrane's Q test and the Higgins and Thompson I2 statistics. Results: Our meta-analysis of 13 studies showed that the presence of the two NOS3 gene polymorphisms significantly increased ESRD risk in ADPKD patients with 4a/b gene polymorphism (aa+ab vs. bb: OR=1.95, 95% CI=1.24-3.09, p=0.004). In addition, no significant association was found between the NOS3 894G>T (Glu298Asp) polymorphism and the risk of ESRD in ADPKD patients (GT+TT vs. GG: OR=1.21, 95% CI=0.93-1.58, p=0.157). There was no evidence of publication bias. Conclusions: The findings of the current meta-analysis suggest that NOS3 intron 4a/b polymorphism plays a vital role in the increasing risk of ESRD in ADPKD patients.


Resumo Introdução: Genes da óxido nítrico sintase endotelial (eNOS) têm sido implicados na hemodinâmica renal como potentes reguladores do tônus vascular e pressão arterial. Tem sido vinculado a uma redução nos níveis plasmáticos de óxido nítrico. Realizou-se recentemente vários estudos para investigar o papel de polimorfismos do gene NOS3 e doença renal em estágio terminal (DRET). Entretanto, os resultados ainda não são claros e os mecanismos não estão totalmente definidos. Como resultado, realizamos meta-análise para examinar a relação entre polimorfismo do gene NOS3 e DRET em pacientes com doença renal policística autossômica dominante (DRPAD). Métodos: Para avaliar a relação entre polimorfismo do gene NOS3 e DRET, recuperou-se estudos relevantes publicados entre Setembro-2002 e Dezembro-2020 dos bancos de dados PubMed (Medline), EMBASE, Google Scholar, Web of Science. Calculamos odds ratio (OR) e intervalo de confiança (IC) de 95% utilizando modelo de efeitos fixos. Para avaliar a heterogeneidade dos estudos, utilizamos teste Q de Cochrane e estatísticas I2 de Higgins e Thompson. Resultados: Nossa meta-análise de 13 estudos mostrou que a presença dos dois polimorfismos do gene NOS3 aumentou significativamente o risco de DRET em pacientes com DRPAD com polimorfismo do gene 4a/b (aa+ab vs. bb: OR=1,95; IC 95%=1,24-3,09; p=0,004). Ademais, não encontramos associação significativa entre polimorfismo 894G>T NOS3 (Glu298Asp) e risco de DRET em pacientes com DRPAD (GT+TT vs. GG: OR=1,21; IC 95%=0,93-1,58; p=0,157). Não houve evidência de viés de publicação. Conclusões: Achados da meta-análise atual sugerem que o polimorfismo intron 4a/b do NOS3 desempenha papel vital no aumento do risco de DRET em pacientes com DRPAD.

16.
Arch. argent. pediatr ; 120(3): e142-e146, junio 2022. tab, ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1370735

ABSTRACT

La nefronoptisis es una enfermedad renal quística, de herencia autosómica recesiva, causada por mutaciones en genes que codifican proteínas involucradas en la función de cilios primarios, lo que resulta en enfermedad renal y manifestaciones extrarrenales como degeneración retiniana y fibrosis hepática. Según la edad de desarrollo de enfermedad renal crónica terminal, se describen tres formas clínicas de presentación: infantil, juvenil y adolescente. El diagnóstico se realiza por una prueba genética positiva o una biopsia de riñón que demuestre cambios tubulointersticiales crónicos con un engrosamiento de las membranas basales tubulares. No existe hasta la actualidad una terapia curativa, por lo que el trasplante renal oportuno es determinante en cuanto al pronóstico. Se presenta un paciente de 13 meses de edad con poliuria de 3 meses de evolución, insuficiencia renal, anemia y elevación de transaminasas. Con hallazgos histológicos compatibles en la biopsia renal, se arribó al diagnóstico de nefronoptisis infantil, con afectación hepática


Nephronophthisis is an autosomal recessive cystic kidney disease caused by mutations in genes that encode proteins involved in the primary cilia function, resulting in kidney disease and extrarenal manifestations such as retinal degeneration and liver fibrosis. According to the age of development of end-stage chronic kidney disease, three clinical forms of presentation are described: infantile, juvenile and adolescent. Diagnosis is made by a positive genetic test, or a kidney biopsy demonstrating chronic tubulointerstitial changes with thickening of the tubular basement membranes. At the moment there is no healing therapy, so early kidney transplant is a fundamental tool to improve prognosis.We present a 13-month old male patient with polyuria, kidney failure, anemia and elevated aminotransferases over three months. With compatible histological kidney biopsy, the diagnosis of infantile nephronophthisis with liver involvement was reached.


Subject(s)
Humans , Male , Infant , Kidney Diseases, Cystic/diagnosis , Kidney Diseases, Cystic/genetics , Kidney Diseases, Cystic/pathology , Kidney Diseases , Kidney Failure, Chronic/genetics , Proteins , Genetic Testing
17.
International Journal of Surgery ; (12): 399-404,F3, 2022.
Article in Chinese | WPRIM | ID: wpr-954221

ABSTRACT

Objective:To explore whether prophylactic resection of orthotopic polycystic kidney before allogeneic kidney transplantation can reduce the incidence and severity of perioperative complications in patients with end-stage renal disease due to autosomal dominant polycystic kidney disease (ADPKD), and reduce the difficulty of surgery.Methods:A retrospective case-control study method was used to recruit a total of 27 patients who were diagnosed with ADPKD and underwent allogeneic kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2013 to January 2021, they were divided into prophylactic resection group ( n=19) and non-prophylactic resection group ( n=8) according to whether orthotopic polycystic kidney disease was prophylactic resection before transplantation. Patients in prophylactic resection group underwent orthotopic polycystic kidney resection before transplantation, while patients in non-prophylactic resection group didn′t. The indexes such as hemoglobin, platelet, albumin, left ventricular wall thickness, left ventricular ejection fraction, difficulty of kidney transplantation, average postoperative hospital stay, pain, and complication rate before kidney transplantation were analyzed and compared between the two groups. Measurement data were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for comparison between groups; Chi-square test was used for comparison of enumeration data between groups. Results:There was no significant difference in the general status of hemoglobin, platelets, albumin, left ventricular wall thickness, and left ventricular ejection fraction between the two groups before kidney transplantation ( P>0.05). However, the polycystic kidney volume [(2 409.8±1 899.8) cm 3] in the prophylactic resection group was greater than that in the non-prophylactic resection group [(1 340.2±290.6) cm 3], and the difference was statistically significant ( P=0.027). In terms of postoperative complications, 9 patients in the prophylactic resection group and 5 patients in the non-prophylactic resection group developed long-term low back pain or hematuria after transplantation, which were considered to be related to the unresected polycystic kidney disease, but the difference was not statistically significant ( P=0.678). Meanwhile, in both two groups, 3 patients underwent orthotopic polycystic nephrectomy after transplantation due to severe polycystic kidney complications. Although the incidence of complications in the prophylactic resection group (15.8%) was lower than that in the non-prophylactic resection group (37.5%), the difference was not statistically significant ( P=0.319). Conclusion:Prophylactic resection of orthotopic polycystic kidney before kidney transplantation can reduce the incidence and severity of polycystic kidney-related complications after transplantation, but has little effect on the operation time and intraoperative blood loss of kidney transplantation.

18.
International Journal of Surgery ; (12): 680-684, 2022.
Article in Chinese | WPRIM | ID: wpr-954275

ABSTRACT

Objective:To evaluate the feasibility and perioperative safety of retroperitoneal laparoscopic nephrectomy for autosomal dominant polycystic kidney disease (ADPKD) before kidney transplantation.Methods:A total of 22 patients with ADPKD who underwent laparoscopic polycystic nephrectomy before kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2013 to December 2020 were enrolled in this retrospective study. Preoperative epidemiological data, operation time, intraoperative blood loss, perioperative blood transfusion, conversion rate, postoperative gastrointestinal function recovery time, drainage tube placement time, postoperative hospital stay, incidence and severity of complications were collected.Results:The mean age of all patients in this study was (50.95±9.28) years old, and the mean preoperative polycystic kidney diameter was (18.83±2.38) cm. In all patients, 20 patients were scheduled for polycystic nephrectomy due to transplantation and 2 patients were done for polycystic renal cyst rupture and hemorrhage. The mean operation time of all patients was (191.14±70.46) min, and the median intraoperative blood loss was 100 mL. Among them, 5 patients had large intraoperative blood loss, and were given intraoperative blood transfusion. Two of all patients were converted to open due to severe intraoperative adhesions. In terms of postoperative recovery, the mean recovery time of gastrointestinal function was (2.09±0.61) d, the mean time of abdominal drainage tube placement was (5.32±2.08) d, the mean postoperative hospital stay was (7.55±2.34) d. In terms of postoperative complications, 4 patients developed postoperative incision pain, bleeding or other complications, but all improved after symptomatic treatment.Conclusions:For patients with ADPKD, original polycystic kidney can be effectively resected by retroperitoneoscopy before transplantation. At the same time, the operation time is short, and patients have quick postoperative recovery, even the incidence and severity of postoperative complications are low. Therefore, retroperitoneal laparoscopic nephrectomy can be used as the first choice for the removal of original polycystic kidney before renal transplantation in ADPKD patients.

19.
Chinese Journal of Neurology ; (12): 1135-1142, 2022.
Article in Chinese | WPRIM | ID: wpr-958009

ABSTRACT

Objective:To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome, so as to improve the clinical understanding of the disease.Methods:A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively. The clinical data, laboratory examination, imaging characteristics and gene variation characteristics of the child were summarized.Results:The patient was a 17 months old girl, with the main complaint of "intermittent convulsion with 17 months of underdevelopment". The clinical manifestations were epileptic seizures, which were in the form of a series of spastic seizures, absence seizures, focal seizures, and depigmentation spots can be seen in the trunk and neck. Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres, multiple small nodular shadows under the ependyma of the bilateral lateral ventricles, the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion, and the abdomen color Doppler ultrasound showed polycystic kidney. Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye. The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene (NM_000548) at chromosome position chr16: 2125799-2185690. The real-time quantitative detection system verified that exons 23-42 were deleted, and all exons of PKD1 gene were deleted (NM_001009944), and multiple ligation dependent probe amplification verified that exons 1-46 were deleted, and no downstream gene deletion was found. The overall deletion size was about 60 kb. Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions:TSC2/PKD1 adjacency gene syndrome is relatively rare. It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease. Most of the nervous system and kidney are seriously affected, and the prognosis is poor. TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.

20.
Chinese Journal of Nephrology ; (12): 685-692, 2022.
Article in Chinese | WPRIM | ID: wpr-958069

ABSTRACT

Objective:To explore the clinical characteristics of autosomal dominant polycystic kidney disease (ADPKD).Methods:Clinical data of 103 patients with ADPKD first admitted to Renmin Hospital of Wuhan University from July 2017 to April 2021 were retrospectively analyzed. The clinical characteristics of patients in different renal function stages were analyzed, and multiple linear regression analysis was used to analyze the factors reflecting the severity of the disease.Results:Among the 103 patients with ADPKD, there were 49 males (47.6%), aged (51.23±10.99) years old. The extrarenal manifestation was mainly polycystic liver (64/71). The main clinical symptoms were gross hematuria (25 cases, 24.3%), lumbar distend and pain (37 cases, 35.9%) and hypertension (69 cases, 67.0%), appearing in the whole course of the disease. Early treatment was mainly drug conservative treatments (58 cases, 56.3%), followed by renal cyst aspiration (34 cases, 33.0%), and surgical treatments (11 cases, 10.7%). Patients in chronic kidney disease (CKD) stage 5 were mainly treated with conservative treatments (28/34). Laboratory examination results showed that hemoglobin, platelet, lymphocyte percentage and albumin in CKD stage 4-5 were lower than those in CKD stage 1-3 (all P<0.05) ; prothrombin time (PT), PT-international standardized ratio and plasma osmotic concentration in CKD stage 4-5 were higher than those in CKD stage 1-3 (all P<0.05). Multiple linear regression analysis showed that hemoglobin ( β=0.249, P=0.005), platelet ( β=0.207, P=0.005), lymphocyte percentage ( β=0.305, P<0.001) and plasma osmotic concentration ( β=-0.362, P<0.001) were correlated with estimated glomerular filtration rate. Conclusions:The clinical manifestations of ADPKD patients are hypertension, lumbar distend and pain, and gross hematuria, which can run through the whole stage of CKD. Polycystic liver is more common in extrarenal system. Hemoglobin, platelets, lymphocyte percentage and concentration osmotic concentration may be related to the disease progression of ADPKD.

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