Cardiac Manifestations in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD): A Single-Center Study.
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SUBMITTER: Arjune S
PROVIDER: S-EPMC10103268 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Cardiac Manifestations in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD): A Single-Center Study.
Arjune Sita S Grundmann Franziska F Todorova Polina P Todorova Polina P Hendrix Claudia C Pfister Roman R Ten Freyhaus Henrik H Müller Roman-Ulrich RU
Kidney360 20221018 2
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| S-EPMC11756268 | biostudies-literature
Project description:BackgroundADPKD is the most prevalent monogenic kidney disease with an estimated incidence of 1:1000. The condition is characterized by the formation of kidney cysts, which can cause kidney function loss and bear a significant risk of advancing to kidney failure. This study examined the prevalence of hepatic cysts in individuals with ADPKD, and the possible influence of these cysts on liver function and quality of life. Furthermore, the relationship between hepatic cysts and genotype was analysed.MethodsClinical data from 880 patients with ADPKD were analysed, including longitudinal patient data, genetic information, and laboratory parameters.ResultsThe prevalence of hepatic cysts in adult ADPKD patients was 81.71%, consistent with previous studies. Prevalence increased with age, particularly in male patients. No clear association was observed between ADPKD genotype and the presence of liver cysts. Among male patients with liver cysts, glutamate pyruvate transaminase (GPT) levels significantly decreased with age, while female patients showed a significant increase in gamma-glutamyl transferase (γ-GT) levels. Overall, hepatic cysts had minimal impact on liver enzymes. Quality of life assessments using the SF-12 questionnaire revealed no significant influence of hepatic cysts on physical or mental well-being. However, physical quality of life was significantly lower in patients showing polycystic liver disease as a manifestation of ADPKD compared to all other patients, both with and without liver cysts.ConclusionsHepatic cysts are highly prevalent in adult patients with ADPKD, increasing with age. ADPKD genotype does not appear to be associated with the presence of hepatic cysts. Liver function, as indicated by enzyme levels, is minimally affected by hepatic cysts in most ADPKD patients. The quality of life of ADPKD patients is generally unaffected by the presence of hepatic cysts, except in severe cases of polycystic liver disease (PLD). Further research is needed to develop effective treatments for severe PLD and gain a better understanding of the factors influencing hepatic cyst incidence and progression in patients with ADPKD.
| S-EPMC11852259 | biostudies-literature
Project description:BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD), a common of monogenetic disorder caused by the polycystic kidney disease-1 (PKD1) or PKD2 genes deficiency. In this study, we have re-analyzed a microarray dataset to generate a holistic view of this disease. METHODOLOGY:GSE7869, an expression profiling dataset was downloaded from the Gene Expression Omnibus (GEO) database. After quality control assessment, using GEO2R tool of GEO, genes with adjusted p-value ≤ 0.05 were determined as differentially expressed (DE). The expression profiles from ADPKD samples in different sizes were compared. Using CluePedia plugin of Cytoscape software, the protein-protein interaction (PPI) networks were constructed and analyzed by Cytoscape NetworkAnalyzer tool and MCODE application. Pathway enrichment analysis of clustered genes by MCODE with the high centrality parameters in PPI networks was performed using Cytoscape ClueGO plugin. Moreover, by Enrichr database, microRNAs (miRNAs) and transcription factors (TFs) targeted DE genes were identified. RESULTS:In this study to explore the molecular pathogenesis of kidney in ADPKD, mRNA expression profiles of cysts from patients in different sizes were re-analyzed. The comparisons were performed between normal with minimally cystic tissue (MCT) samples, MCTs with small cysts, and small cysts with large cysts. 512, 7024, and 655 DE genes were determined, respectively. The top central genes, e.g. END1, EGFR, and FOXO1 were identified with topology and clustering analysis. DE genes that were significantly enriched in PPI networks are critical genes and their roles in ADPKD remain to be assessed in future experimental studies beside miRNAs and TFs predicted. Furthermore, the functional analysis resulted in which most of them are expected to be associated with ADPKD pathogenesis, such as signal pathways that involved in cell growth, inflammation, and cell polarity. CONCLUSION:We have here explored systematic approaches for molecular mechanisms assay of ADPKD as a monogenic disease, which may also be used for other monogenetic diseases beside complex diseases to provide suitable therapeutic targets.
| S-EPMC6944722 | biostudies-literature
Project description:ADPKD is caused by pathogenic variants in PKD1 or PKD2, encoding polycystin-1 and -2 proteins. Polycystins are expressed in osteoblasts and chondrocytes in animal models, and loss of function is associated with low bone mineral density (BMD) and volume. However, it is unclear whether these variants impact bone strength in ADPKD patients. Here, we examined BMD in ADPKD after kidney transplantation (KTx). This retrospective observational study retrieved data from adult patients who received a KTx over the past 15 years. Patients with available dual-energy X-ray absorptiometry (DXA) of the hip and/or lumbar spine (LS) post-transplant were included. ADPKD patients (n = 340) were matched 1:1 by age (±2 years) at KTx and sex with non-diabetic non-ADPKD patients (n = 340). Patients with ADPKD had slightly higher BMD and T-scores at the right total hip (TH) as compared to non-ADPKD patients [BMD: 0.951 vs. 0.897, p < 0.001; T-score: -0.62 vs. -0.99, p < 0.001] and at left TH [BMD: 0.960 vs. 0.893, p < 0.001; T-score: -0.60 vs. -1.08, p < 0.001], respectively. Similar results were found at the right femoral neck (FN) between ADPKD and non-ADPKD [BMD: 0.887 vs. 0.848, p = 0.001; T-score: -1.20 vs. -1.41, p = 0.01] and at left FN [BMD: 0.885 vs. 0.840, p < 0.001; T-score: -1.16 vs. -1.46, p = 0.001]. At the LS level, ADPKD had a similar BMD and lower T-score compared to non-ADPKD [BMD: 1.120 vs. 1.126, p = 0.93; T-score: -0.66 vs. -0.23, p = 0.008]. After adjusting for preemptive KTx, ADPKD patients continued to have higher BMD T-scores in TH and FN. Our findings indicate that BMD by DXA is higher in patients with ADPKD compared to non-ADPKD patients after transplantation in sites where cortical but not trabecular bone is predominant. The clinical benefit of the preserved cortical bone BMD in patients with ADPKD needs to be explored in future studies.
| S-EPMC9842864 | biostudies-literature
Project description:Autosomal-dominant polycystic kidney disease (ADPKD) is associated with progressive formation of renal cysts, kidney enlargement, hypertension, and typically end-stage renal disease. In ADPKD, inherited mutations disrupt function of the polycystins (encoded by PKD1 and PKD2), thus causing loss of a cyst-repressive signal emanating from the renal cilium. Genetic studies have suggested ciliary maintenance is essential for ADPKD pathogenesis. Heat shock protein 90 (HSP90) clients include multiple proteins linked to ciliary maintenance. We determined that ganetespib, a clinical HSP90 inhibitor, inhibited proteasomal repression of NEK8 and the Aurora-A activator trichoplein, rapidly activating Aurora-A kinase and causing ciliary loss in vitro. Using conditional mouse models for ADPKD, we performed long-term (10 or 50 wk) dosing experiments that demonstrated HSP90 inhibition caused durable in vivo loss of cilia, controlled cystic growth, and ameliorated symptoms induced by loss of Pkd1 or Pkd2. Ganetespib efficacy was not increased by combination with 2-deoxy-d-glucose, a glycolysis inhibitor showing some promise for ADPKD. These studies identify a new biologic activity for HSP90 and support a cilia-based mechanism for cyst repression.-Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korobeynikov, V., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger-Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD).
| S-EPMC5901382 | biostudies-literature
Project description:Background and objectivesAutosomal dominant polycystic kidney disease (ADPKD) occurs at conception and is often diagnosed decades prior to kidney failure. Nephrology care and transplantation access should be independent of race and ethnicity. However, institutional racism and barriers to health care may affect patient outcomes in ADPKD. We sought to ascertain the effect of health disparities on outcomes in ADPKD by examining age at onset of kidney failure and access to preemptive transplantation and transplantation after dialysis initiation.Design, setting, participants, & measurementsRetrospective cohort analyses of adults with ADPKD in the United States Renal Data System from January 2000 to June 2018 were merged to US Census income data and evaluated by self-reported race and ethnicity. Age at kidney failure was analyzed in a linear model, and transplant rates before and after dialysis initiation were analyzed in logistic and proportional hazards models in Black and Hispanic patients with ADPKD compared with White patients with ADPKD.ResultsA total of 41,485 patients with ADPKD were followed for a median of 25 (interquartile range, 5-54) months. Mean age was 56±12 years; 46% were women, 13% were Black, and 10% were Hispanic. Mean ages at kidney failure were 55±13, 53±12, and 57±12 years for Black patients, Hispanic patients, and White patients, respectively. Odds ratios for preemptive transplant were 0.33 (95% confidence interval, 0.29 to 0.38) for Black patients and 0.50 (95% confidence interval, 0.44 to 0.56) for Hispanic patients compared with White patients. Transplant after dialysis initiation was 0.61 (95% confidence interval, 0.58 to 0.64) for Black patients and 0.78 (95% confidence interval, 0.74 to 0.83) for Hispanic patients.ConclusionsBlack and Hispanic patients with ADPKD reach kidney failure earlier and are less likely to receive a kidney transplant preemptively and after initiating dialysis compared with White patients with ADPKD.
| S-EPMC9269641 | biostudies-literature
Project description:To elucidate the molecular pathways that modulate renal cyst growth in autosomal dominant polycystic kidney disease (ADPKD) Keywords: Disease state analysis We performed global gene profiling on renal cysts of different size (small cysts: less than 1 ml, n=5; medium cysts: between 10-25 ml, n=5; large cysts: greater than 50 ml, n=3) and minimally cystic tissue (MCT, n=5) from five PKD1 polycystic kidneys. Additionally, non-cancerous renal cortical tissue from three nephrectomized kidneys with isolated renal cell carcinoma was used as normal control tissue (n=3). This dataset is part of the TransQST collection.
2009-08-14 | E-GEOD-7869 | biostudies-arrayexpress
Project description:BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD); however, the natural course of disease progression is heterogeneous between patients. This study aimed to develop a natural history model of ADPKD that predicted progression rates and long-term outcomes in patients with differing baseline characteristics. METHODS:The ADPKD Outcomes Model (ADPKD-OM) was developed using available patient-level data from the placebo arm of the Tolvaptan Efficacy and Safety in Management of ADPKD and its Outcomes Study (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948). Multivariable regression equations estimating annual rates of ADPKD progression, in terms of total kidney volume (TKV) and estimated glomerular filtration rate, formed the basis of the lifetime patient-level simulation model. Outputs of the ADPKD-OM were compared against external data sources to validate model accuracy and generalisability to other ADPKD patient populations, then used to predict long-term outcomes in a cohort matched to the overall TEMPO 3:4 study population. RESULTS:A cohort with baseline patient characteristics consistent with TEMPO 3:4 was predicted to reach ESRD at a mean age of 52 years. Most patients (85%) were predicted to reach ESRD by the age of 65 years, with many progressing to ESRD earlier in life (18, 36 and 56% by the age of 45, 50 and 55 years, respectively). Consistent with previous research and clinical opinion, analyses supported the selection of baseline TKV as a prognostic factor for ADPKD progression, and demonstrated its value as a strong predictor of future ESRD risk. Validation exercises and illustrative analyses confirmed the ability of the ADPKD-OM to accurately predict disease progression towards ESRD across a range of clinically-relevant patient profiles. CONCLUSIONS:The ADPKD-OM represents a robust tool to predict natural disease progression and long-term outcomes in ADPKD patients, based on readily available and/or measurable clinical characteristics. In conjunction with clinical judgement, it has the potential to support decision-making in research and clinical practice.
| S-EPMC5810027 | biostudies-literature
Project description:BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is an inherited condition caused by PKD1 and PKD2 mutations. Complete analysis of both genes is typically required in each patient. In this study, we explored the utility of High-Resolution Melt (HRM) as a tool for mutation analysis of the PKD2 gene in ADPKD families.MethodsHRM is a mismatch-detection method based on the difference of fluorescence absorbance behavior during the melting of the DNA double strand to denatured single strands in a mutant sample as compared to a reference control. Our families were previously screened by linkage analysis. Subsequently, HRM was used to characterize PKD2-linked families. Amplicons that produced an overlapping profile sample versus wild-type control were not further evaluated, while those amplicons with profile deviated from the control were consequently sequenced.ResultsWe analyzed 16 PKD2-linked families by HRM analysis. We observed ten different variations: six single-nucleotide polymorphisms and four mutations. The mutations detected by HRM and confirmed by sequencing were as follows: 1158T>A, 2159delA, 2224C>T, and 2533C>T. In particular, the same haplotype block and nonsense mutation 2533C>T was found in 8 of 16 families, so we suggested the presence of a founder effect in our province.ConclusionsWe have developed a strategy for rapid mutation analysis of the PKD2 gene in ADPKD families, which utilizes an HRM-based prescreening followed by direct sequencing of amplicons with abnormal profiles. This is a simple and good technique for PKD2 genotyping and may significantly reduce the time and cost for diagnosis in ADPKD.
| S-EPMC6807430 | biostudies-literature
Project description:To elucidate the molecular pathways that modulate renal cyst growth in autosomal dominant polycystic kidney disease (ADPKD) Keywords: Disease state analysis
2009-08-14 | GSE7869 | GEO