Early onset gout and chronic kidney disease in a young female patient.
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ABSTRACT:
SUBMITTER: Cao Y
PROVIDER: S-EPMC8104136 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Autosomal Dominant Polycystic Kidney Disease (ADPKD) typically results from a mutation in the PKD1 and PKD2 genes, which code for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Mutations in these genes promote renal cystic dysplasia and are a significant cause of End-Stage Kidney Disease (ESKD). Polycystic kidney disease-3 (PKD3), another form of ADPKD, is caused by mutations in glucosidase II alpha subunit (GANAB) gene and present in mid- and late adulthood. We report a description of an ADPKD case in a 12-year-old female presented bilateral renal cysts in adolescence. Two mutations in two genes PKD1 and GANAB were identified by targeted capture and next-generation sequencing (NGS) on an Illumina sequencing system. The identified PKD1 mutation p.Pro61Leu: c.182C > T (CCC > CTC) a missense type of uncertain clinical significance. However, the identified PKD1 mutation can alter transcription factors motifs and consequently disturb the transcription process. The second mutation identified in GANAB locus, p.Arg61Ter: c.181C > T, a nonsense type, CGA > TGA. The mutation is unreported pathogenic variant can cause loss of the glucosidase II alpha subunit normal protein function. Both the patient father and paternal grandmother had a history of ADPKD but never were tested. This case is the first case of combine presentation on PKD1 and PKD3 in a pediatric patient with nephrolithiasis.
| S-EPMC6375066 | biostudies-literature
Project description:ImportanceClinicians are often cautious about use of allopurinol in patients with gout when renal function declines.ObjectiveTo assess the association of allopurinol use in gout with the risk of developing chronic kidney disease stage 3 or higher.Design, setting, and participantsA time-stratified propensity score-matched, population-based, prospective cohort study of individuals with newly diagnosed gout who initiated allopurinol (≥300 mg/d) compared with those who did not initiate allopurinol, using the Health Improvement Network (THIN), a United Kingdom general practitioner electronic health records database, was carried out. The data were analyzed using Cox proportional hazards regression. Among adults aged 18 to 89 years with newly diagnosed gout, we propensity score matched 4760 initiators of allopurinol (≥300 mg/d) to the same number of noninitiators of allopurinol, excluding those with chronic kidney disease stage 3 or higher or urate-lowering therapy use before their gout diagnosis.ExposuresAllopurinol initiation at a dose of 300 mg or more per day.Main outcomes and measuresDevelopment of chronic kidney disease stage 3 or higher.ResultsOf the 4760 allopurinol initiators (3975 men, 785 women) and same number of noninitiators (3971 men, 789 women), 579 and 623, respectively, developed chronic kidney disease stage 3 or higher, with a mean follow-up time of 5 and 4 years, mean age of 57 years, and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 for both groups. Use of allopurinol of at least 300 mg/d was associated with lower risk of developing chronic kidney disease stage 3 or higher compared with nonusers, with a hazard ratio (HR) of 0.87 (95% CI, 0.77-0.97). Allopurinol initiation at less than 300 mg/d was not associated with renal function decline (HR, 1.00; 95% CI, 0.91-1.09).Conclusions and relevanceIn this large cohort, allopurinol initiation of at least 300 mg/d was associated with a lower risk of renal function deterioration. Because allopurinol does not appear to be associated with renal function decline, clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.
| S-EPMC6248199 | biostudies-literature
Project description:Early?onset cardiovascular and renal diseases have a strong genetic component. In the present study, exome?wide association studies (EWASs) were performed to identify genetic variants that confer susceptibility to early?onset myocardial infarction (MI), hypertension, or chronic kidney disease (CKD) in Japanese individuals. A total of 8,093 individuals aged ?65 years was enrolled in the study. The EWASs for MI, hypertension, and CKD were performed in 6,926 subjects (1,152 cases, 5,774 controls), 8,080 subjects (3,444 cases, 4,636 controls), and 2,556 subjects (1,051 cases, 1,505 controls), respectively. Genotyping of single nucleotide polymorphisms (SNPs) was performed with Illumina Human Exome?12 DNA Analysis BeadChip or Infinium Exome?24 BeadChip arrays. The associations of allele frequencies for 31,245, 31,276, or 31,514 SNPs that passed quality control to MI, hypertension, and CKD, respectively, was examined with Fisher's exact test. Bonferroni's correction for statistical significance of association was applied to compensate for multiple comparisons of genotypes with MI, hypertension, or CKD. The EWASs of allele frequencies revealed that 25, 11, and 11 SNPs were significantly associated with MI (P<1.60x10?6), hypertension (P<1.60x10?6), or CKD (P<1.59x10?6), respectively. Multivariable logistic regression analysis with adjustment for covariates showed that all 25, 11, and 11 SNPs were significantly associated with MI (P<0.0005), hypertension (P<0.0011), or CKD (P<0.0011), respectively. On examination of the results from previous genome?wide association studies and linkage disequilibrium of the identified SNPs, 11 loci (TMOD4, COL6A3, ADGRL3?CXCL8?MARCH1, OR52E4, TCHP?GIT2, CCDC63, 12q24.1, OAS3, PLCB2?VPS33B, GOSR2, ZNF77), six loci (MOB3C?TMOD4, COL6A3, COL6A5, CXCL8?MARCH1, NFKBIL1?6p21.3?NCR3, PLCB2?VPS33B), and seven loci (MOB3C?TMOD4, COL6A3, COL6A5, ADGRL3?CXCL8?MARCH1, MUC17, PLCB2?VPS33B, ZNF77) were identified as novel loci significantly associated with MI, hypertension, and CKD, respectively. Furthermore, six genes (TMOD4, COL6A3, CXCL8, MARCH1, PLCB2, VPS33B) were significantly associated with MI, hypertension and CKD; two genes (ADGRL3, ZNF77) with MI and CKD; and two genes (COL6A5, MOB3C) with hypertension and CKD. Therefore, 13 novel loci (MOB3C?TMOD4, COL6A3, ADGRL3?CXCL8?MARCH1, OR52E4, TCHP?GIT2, CCDC63, 12q24.1, OAS3, PLCB2?VPS33B, ZNF77, COL6A5, NFKBIL1?NCR3, MUC17) were identified that confer susceptibility to early?onset MI, hypertension, or CKD. The determination of genotypes for the SNPs at these loci may provide informative for assessment of the genetic risk for MI, hypertension, or CKD.
| S-EPMC6192728 | biostudies-literature
Project description:Interventions: All eligible participants will receive an imunochemical faecal occult blood test (IFOBT) kit (EIKEN brand) containing the test and instructions, with additional explanation provided by study staff, as required. A sample is then collected from two separate bowel motions. All samples will be self-collected.
All completed kits will be sent and processed in a designated central laboratory and analysed according to the company’s standardised specifications. The results of this test can be positive, negative or inconclusive. All results will be sent via mail to the corresponding treating physicians, the participants and the research assistants at the Centre for Kidney Research. The screen is considered positive when one of the samples contains at least 50ng/ml of haemoglobin. Negative results are not followed up in the study but these patients are advised to continue with annual screening with their health practitioner. If the results are inconclusive, the participants will be contacted by phone and asked to repeat the test.
Only participants with positive IFOBT findings will be referred for a diagnostic colonoscopy at a designated colonoscopic service. Study staff will track participants with positive IFOBT results and will ensure the referral process is scheduled effectively and efficiently for a colonoscopy. The participants will not be required to pay for the IFOBT kit or the diagnostic colonoscopy. Other clinical significant pathologies such as polyps, adenomas, vascular lesions will be documented and recorded. Wherever possible, they will be resected and sent for pathology. Depending upon the stage of initial diagnosis, further treatment may be required for participants with malignant polyps and cancers. All cancer diagnoses, including stage, histologica
Primary outcome(s): Prevalence of a positive screening result (defined as positive IFOBT with at least one of the two stool samples containing at least 50ng/ml of haemoglobin) in people with chronic kidney disease in stages 3-5, dialysis and kidney transplant populations using the immunochemical faecal occult blood test. [Five years];Prevalence of colorectal cancer as determined with diagnostic colonoscopy, in people with chronic kidney disease in stages 3-5, dialysis and kidney transplant populations.[Five years];Test performance characteristics of immunochemical faecal occult blood screening, including: test specificity, positive predictive values and negative predictive value for colorectal cancers. [Five years]
Study Design: Purpose: Diagnosis; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety/efficacy
| 2456994 | ecrin-mdr-crc
Project description:OBJECTIVE:The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors. SUMMARY OF BACKGROUND DATA:Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs). METHODS:We identified a cohort of young adults (18-30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60?mL/min/1.73?m) were identified and assigned weighted points to calculate risk scores. RESULTS:A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5-25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men. CONCLUSIONS:Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.
| S-EPMC5805656 | biostudies-literature
Project description:A retrospective cross-sectional study using data from an outpatient clinic in China was conducted to investigate the clinical features of early-onset gout patients.All patients diagnosed with gout were asked about clinical characteristics of their gout and comorbid diseases. Patients presenting with acute flares were asked about common triggers before the flare. "Early-onset" gout was defined as onset of gout before 40 years and "late-onset" as onset ?40 years. Major joint involvement, flare frequency before presentation, the cumulative number of involved joints, proportions of tophi complications at presentation, flare triggers, as well as any metabolic, cardiovascular, cerebrovascular, and renal comorbidities, were compared between the 2 groups.A total of 778 gout patients were enrolled in this study, including 449 (57.7%) in the early-onset group and 329 (42.3%) in the late-onset group. Compared with the late-onset gout patients, the early-onset gout patients had a higher proportion of ankle/mid-foot involvement (62.8% vs 48.2%, P?<?0.001), more frequent flares before presentation (11.2?±?1.17 vs 6.97?±?1.03 times per year, P?=?0.01), higher cumulative number of involved joints (5.2?±?0.26 vs 3.8?±?0.26, P?<?0.001), and more likely to have alcohol consumption as a flare trigger (65.2% vs 53.9%, P?=?0.03); whereas early-onset gout patients had fewer metabolic, cardiovascular, cerebrovascular, or renal complications.Early- and late-onset gout patients had different clinical features. Early-onset seems to be influenced more by lifestyle, while late-onset patients have more complications because of comorbidities.
| S-EPMC5134876 | biostudies-other
Project description:The clinical manifestation of frontal-variant Alzheimer's disease (fvAD) is not typical, and it is difficult yet necessary to differentiate fvAD from frontal-variant frontal temporal dementia (fvFTD). We describe a patient with early-onset Alzheimer's disease (AD) who presented with an fvFTD-like syndrome and apolipoprotein E ɛ3/ ɛ4 genotype. A brain amyloid imaging procedure, 11C-Pittsburgh compound B positron emission tomography (PET), supported the final diagnosis of AD. Our present case highlights the clinical variability that characterises early-onset AD. A multimodal approach is crucial when assessing rare forms of dementia.
| S-EPMC7078674 | biostudies-literature
Project description:Chronic kidney disease (CKD) is a complex debilitating condition affecting more than 70 million people worldwide. With the increased prevalence in risk factors such as diabetes, hypertension, and cardiovascular disease in an aging population, CKD prevalence is also expected to increase. Increased awareness and understanding of the overall CKD burden by health care teams (patients, clinicians, and payers) is warranted so that overall care and treatment management may improve. This review of the burden of CKD summarizes available evidence of the clinical, humanistic, and economic burden of CKD and the current unmet need for new treatments and serves as a resource on the overall burden. Across countries, CKD prevalence varies considerably and is dependent upon patient characteristics. The prevalence of risk factors including diabetes, hypertension, cardiovascular disease, and congestive heart failure is noticeably higher in patients with lower estimated glomerular filtration rates (eGFRs) and results in highly complex CKD patient populations. As CKD severity worsens, there is a subsequent decline in patient health-related quality of life and an increased use of health care resources as well as burgeoning costs. With current treatment, nearly half of patients progress to unfavorable renal and cardiovascular outcomes. Although curative treatment that will arrest kidney deterioration is desired, innovative agents under investigation for CKD to slow kidney deterioration, such as atrasentan, bardoxolone methyl, and spherical carbon adsorbent, may offer patients healthier and more productive lives.
| S-EPMC3534533 | biostudies-other
Project description:Moderate overexpression of Opa1, the master regulator of mitochondrial cristae morphology, significantly improved mitochondrial damage induced by drugs, surgical denervation, or oxidative phosphorylation (OXPHOS) defects due to specific impairment of a single mitochondrial respiratory chain complex. Here, we investigated the effectiveness of this approach in the Mpv17-/- mouse, characterized by profound, multisystem mitochondrial DNA (mtDNA) depletion. After the crossing with Opa1tg mice, we found a surprising anticipation of the severe, progressive focal segmental glomerulosclerosis, previously described in Mpv17-/- animals as a late-onset clinical feature (after 12-18 months of life). In contrast, Mpv17-/- animals from this new "mixed" strain died at 8-9 weeks after birth because of severe kidney failure However, Mpv17-/-::Opa1tg mice lived much longer than Mpv17-/- littermates and developed the kidney dysfunction much later. mtDNA content and OXPHOS activities were significantly higher in Mpv17-/-::Opa1tg than in Mpv17-/- kidneys and similar to those for wild-type (WT) littermates. Mitochondrial network and cristae ultrastructure were largely preserved in Mpv17-/-::Opa1tg versus Mpv17-/- kidney and isolated podocytes. Mechanistically, the protective effect of Opa1 overexpression in this model was mediated by a block in apoptosis due to the stabilization of the mitochondrial cristae. These results demonstrate that strategies aiming at increasing Opa1 expression or activity can be effective against mtDNA depletion syndromes.
| S-EPMC7403474 | biostudies-literature
Project description:Gout and chronic kidney disease (CKD) frequently coexist, but quality evidence to guide gout management in people with CKD is lacking. Use of urate-lowering therapy (ULT) in the context of advanced CKD varies greatly, and professional bodies have issued conflicting recommendations regarding the treatment of gout in people with concomitant CKD. As a result, confusion exists among medical professionals about the appropriate management of people with gout and CKD. This Consensus Statement from the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) discusses the evidence and/or lack thereof for the management of gout in people with CKD and identifies key areas for research to address the challenges faced in the management of gout and CKD. These discussions, which address areas for research both in general as well as related to specific medications used to treat gout flares or as ULT, are supported by separately published G-CAN systematic literature reviews. This Consensus Statement is not intended as a guideline for the management of gout in CKD; rather, it analyses the available literature on the safety and efficacy of drugs used in gout management to identify important gaps in knowledge and associated areas for research.
| S-EPMC8458096 | biostudies-literature