Familial hematuria.
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ABSTRACT:
SUBMITTER: Kashtan CE
PROVIDER: S-EPMC2731159 | biostudies-other | 2009 Oct
REPOSITORIES: biostudies-other
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Project description:Familial hematuria (FH) is explained by at least four different genes (see below). About 50% of patients develop late proteinuria and chronic kidney disease (CKD). We hypothesized that MYH9/APOL1, two closely linked genes associated with CKD, may be associated with adverse progression in FH. Our study included 102 thin basement membrane nephropathy (TBMN) patients with three known COL4A3/COL4A4 mutations (cohort A), 83 CFHR5/C3 glomerulopathy patients (cohort B) with a single CFHR5 mutation and 15 Alport syndrome patients (cohort C) with two known COL4A5 mild mutations, who were categorized as "Mild" (controls) or "Severe" (cases), based on renal manifestations. E1 and S1 MYH9 haplotypes and variant rs11089788 were analyzed for association with disease phenotype. Evidence for association with "Severe" progression in CFHR5 nephropathy was found with MYH9 variant rs11089788 and was confirmed in an independent FH cohort, D (cumulative p value = 0.001, odds ratio = 3.06, recessive model). No association was found with APOL1 gene. Quantitative Real time PCR did not reveal any functional significance for the rs11089788 risk allele. Our results derive additional evidence supporting previous reports according to which MYH9 is an important gene per se, predisposing to CKD, suggesting its usefulness as a prognostic marker for young hematuric patients.
| S-EPMC3597641 | biostudies-literature
Project description:Focal segmental glomerulosclerosis (FSGS) is a pathological lesion rather than a disease, with a diverse etiology. FSGS may result from genetic and non‑genetic factors. FSGS is considered a podocyte disease due to the fact that in the majority of patients with proven‑FSGS, the lesion results from defects in the podocyte structure or function. However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes. Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH). Previous studies revealed that long‑time persistent microscopic hematuria may lead to FSGS. A case of a family is presented here where affected individuals exhibited FH with FSGS‑proven, or chronic kidney disease. Renal biopsies were unhelpful and failed to demonstrate glomerular or basement membrane defects consistent with an inherited glomerulopathy, and therefore a possible underlying genetic cause for a unifying diagnosis was pursued. Genomic DNA of the siblings affected by FH with biopsy‑proven FSGS was analyzed, and their father was screened for 18 gene mutations associated with FSGS [nephrin, podocin, CD2 associated protein, phospholipase C ε, actinin α 4, transient receptor potential cation channel subfamily C member 6, inverted formin, FH2 and WH2 domain containing, Wilms tumor 1, LIM homeobox transcription factor 1 β, laminin subunit β 2, laminin subunit β 3, galactosida α, integrin subunit β 4, scavenger receptor class B member 2, coenzyme Q2, decaprenyl diphosphate synthase subunit 2, mitochondrially encoded tRNA leucine 1 (UUA/G; TRNL1) and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1] using matrix‑assisted laser desorption/ionization time‑of‑flight mass spectrometry technology. Then whole exome sequencing (WES) was performed in the two probands to ascertain whether there were other known or unknown gene mutations that segregated with the disease. Using mass array technology, a TRNL1 missense homozygous mutation (m. 3290T>C) was identified in the probands diagnosed with FH and manifested as FSGS on biopsy. In addition, a COL4A4 missense mutation c. 4195A>T (p. M1399L) in heterozygous pattern was identified using WES. None of these variants were detected in their father. In the present study, a mutation in TRNL1 (m. 3290T>C) was identified, which was the first reported variant associated with FSGS. The COL4A4 (c. 4195A>T) may co‑segregate with FSGS. Screening for COL4A mutations in familial FSGS patients is suggested in the present study. Genetic investigations of families with similar clinical phenotypes should be a priority for nephrologists. The combination of mass array technology and WES may improve the detection rate of genetic mutation with a high level of accuracy.
| S-EPMC5780091 | biostudies-literature
Project description:BACKGROUND:About 40-50% of patients with familial microscopic hematuria (FMH) caused by thin basement membrane nephropathy (TBMN) inherit heterozygous mutations in collagen IV genes (COL4A3, COL4A4). On long follow-up, the full phenotypic spectrum of these patients varies a lot, ranging from isolated MH or MH plus low-grade proteinuria to chronic renal failure of variable degree, including end-stage renal disease (ESRD). METHODS:Here, we performed Whole Exome Sequencing (WES) in patients of six families, presenting with autosomal dominant FMH, with or without progression to proteinuria and loss of renal function, all previously found negative for severe collagen IV mutations. Hierarchical filtering of the WES data was performed, followed by mutation prediction analysis, Sanger sequencing and genetic segregation analysis. RESULTS:In one family with four patients, we found evidence for the contribution of two co-inherited variants in two crucial genes expressed in the glomerular basement membrane (GBM); LAMA5-p.Pro1243Leu and COL4A5-p.Asp654Tyr. Mutations in COL4A5 cause classical X-linked Alport Syndrome, while rare mutations in the LAMA5 have been reported in patients with focal segmental glomerulosclerosis. The phenotypic spectrum of the patients includes hematuria, proteinuria, focal segmental glomerulosclerosis, loss of kidney function and renal cortical cysts. CONCLUSIONS:A modifier role of LAMA5 on the background of a hypomorphic Alport syndrome causing mutation is a possible explanation of our findings. Digenic inheritance is another scenario, following the concept that mutations at both loci more accurately explain the spectrum of symptoms, but further investigation is needed under this concept. This is the third report linking a LAMA5 variant with human renal disease and expanding the spectrum of genes involved in glomerular pathologies accompanied by familial hematurias. The cystic phenotype overlaps with that of a mouse model, which carried a Lama5 hypomorphic mutation that caused severely reduced Lama5 protein levels and produced kidney cysts.
| S-EPMC5954460 | biostudies-literature
Project description:Wuchereria bancrofti is the major species resulting in filarial cases in India. Filariasis may present with various clinical presentations: asymptomatic, microfilaremia, lymphedema, acute adenolymphangitis and chronic lymphatic disease. Microfilariae of W. bancrofti have been detected in various clinical samples, but incidental detection of microfilaria in achylous urine is a rare finding with unexplained pathology. We report a case of microfilaria in achylous urine of a 30-year-old female who presented with pain abdomen and ureteric calculus on ultrasonography.
| S-EPMC7365504 | biostudies-literature
Project description: Not available
| S-EPMC8548956 | biostudies-literature
Project description:Background:Hematuria is the most common presenting symptom in bladder cancer, but many patients are not adequately evaluated. Objectives:To evaluate the type and frequency of hematuria evaluation in a large public health care system. Patients and Methods:Electronic medical records of adult patients with urinalysis positive for hematuria (?3 RBCs/HPF) from January 2015 to April 2018 in an outpatient setting were reviewed. Logistic regression was performed to determine factors associated with urology referral and complete evaluation. Results:11,422 patients met the inclusion criteria; the majority were females (72%) and white race (60%). There were an additional 3,221 patient's with initial diagnosis of UTI. Median age was 49.0 years. Testing included repeat urinalysis (50%), imaging (26%), urology referral (11.4%), cystoscopy (4.4%) and complete evaluation defined as cystoscopy and US/CT/MRI (4%). In the multivariable analysis, factors independently associated with higher referral to urology were age >35, male gender, hypertension, RBCs ?20. African American race was associated with less referral to urology. Smoking was a significant variable on univariable analysis only. 37 patients (0.25%) were diagnosed with urological malignancies, with bladder cancer in 33, 12 of whom are missed by excluding UTI patients. Conclusions:In the outpatient setting of a public health care system, the vast majority of patients with hematuria are not referred and evaluated properly across all age categories and regardless of smoking status. This might result in missed cancer diagnoses and requires quality improvement measures.
| S-EPMC6953989 | biostudies-literature
Project description:Introduction:Macroscopic hematuria is considered a significant risk factor for urologic disease, and it is highly prevalent in people with hemophilia. Aim:To determine whether prophylactic factor replacement therapy is associated with reduced occurrence of macroscopic hematuria in people with hemophilia in a post hoc analysis using data from a cross-sectional study conducted by the Age-Related Developments and Comobordities in Hemophilia (ADVANCE) Working Group that included males with hemophilia ?40 years of age. Methods:Data from 16 contributing centers, in 13 European countries and Israel, were analyzed using logistic regression. Of 532 recruited individuals, this analysis included 370 patients with moderate or severe hemophilia who received on-demand or prophylactic therapy. Results:For patients with a history of macroscopic hematuria, we analyzed the association between prophylaxis and reoccurrence of macroscopic hematuria within the past 5 years (n = 235 patients). Frequent (?3 times/wk) prophylaxis was negatively associated with a recent episode of macroscopic hematuria (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.18-0.76). We also analyzed whether prophylaxis corresponded to a lower lifetime number of macroscopic hematuria episodes (n = 285 patients). Frequent prophylaxis for >15 years was associated with a lower number of episodes compared to on-demand treatment (OR, 0.29; 95% CI, 0.16-0.54), whereas nonsteroidal anti-inflammatory drugs (NSAIDs) and severe hemophilia were associated with a higher number. There was no association of prophylaxis <3 times/wk with hematuria. Conclusion:Frequent prophylaxis was negatively associated with the number of episodes of macroscopic hematuria in people with hemophilia. Prevalence of macroscopic hematuria was higher among individuals with severe hemophilia and those regularly using NSAIDs.
| S-EPMC7040553 | biostudies-literature
Project description:BackgroundBased on their renal excretion, direct oral anticoagulants (DOACs) may increase the risk of hematuria in patients with atrial fibrillation (AF) and urologic cancer compared with vitamin K antagonists.ObjectivesTo examine the risk of bleeding associated with DOAC versus warfarin in patients with AF and urologic cancer.MethodsWe conducted a Danish nationwide cohort study with individually linked registry data on patients with AF and active or a history of urologic cancer. We calculated crude rates per 100 person-years of hospital episodes of major bleeding and hematuria. We then compared rates of hematuria during the year after initial oral anticoagulation filled prescription by treatment regimen using inverse probability of treatment weighting and Cox regression.ResultsThe study population included 2615 patients with AF and urologic cancer (6.1% women; median age, 76 years) initiating a DOAC or warfarin. One-year risk of hematuria was 4.8% in the DOAC group and 4.7% in the warfarin group with a corresponding weighted hazard ratio (HR) of 1.21 (95% confidence interval [CI], 0.81-1.81). HRs for hematuria were generally similar in analyses restricted to patients treated with standard-dose DOAC and patients with active cancer. For those with cancer of the kidney, renal pelvis, ureter, and bladder, the HR was 0.82 (95% CI, 0.44-1.54). Results were mirrored for other bleeding events, whereas the risk for intracranial bleeding was lower with DOACs.ConclusionIn patients with AF and urologic cancer, there was a similar risk of hematuria associated with DOAC and warfarin treatment.
| S-EPMC8756162 | biostudies-literature
Project description:Chromosome 18 pericentric inversion carriers could have offspring with recombinant chromosomes, leading to patients with clinical variable manifestations. Patients with 18p-/18q+ rearrangements share some clinical characteristics, while other characteristics differ. Factors for such divergence include the length of the inverted segment, among others. Here, we describe a Peruvian child with dysmorphic features, intellectual disability persistent microscopic hematuria, aortic pseudocoarctation, and descending aorta arteritis, among others. Karyotype analysis of family members determined the mother as the carrier of a pericentric inversion: 18[inv(18)(p11.2q21.3)]. This child carries a recombinant chromosome 18, with chromosomal microarray analysis detecting two genomic imbalances in patient's chromosome 18: one duplicated region and one deleted segment in the large and the short arms, respectively. Persistent microscopic hematuria has not been reported among 18p-/18q+ phenotypes. Our patient elucidates that other factors play significant and yet unknown roles for not fulfilling the proposed genotype-phenotype correlation associated with hemizygosity in this type of recombinant chromosome 18 or presenting these features as the patient ages.
| S-EPMC5683951 | biostudies-literature
Project description:BackgroundRecent clinical reports indicate a correlation between gross hematuria after the coronavirus 2019 (COVID-19) vaccination in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). Furthermore, healthcare workers in Japan were initially vaccinated with an mRNA vaccine from February 17, 2021, and some of them experienced gross hematuria after receiving the vaccination.MethodsWe conducted a web-based survey of the councilor members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between gross hematuria and COVID-19 vaccination.ResultsIn the first survey, 27 cases (female: 22, 81.5%) of gross hematuria were reported after receiving a COVID-19 vaccination. Of them, 19 (70.4%) patients were already diagnosed with IgAN at the occurrence of gross hematuria. Proteinuria appeared in eight of the 14 (57.1%) cases with no proteinuria before vaccination and hematuria in five of the seven (71.4%) cases with no hematuria before vaccination. The second survey revealed that a renal biopsy was performed after vaccination in four cases, all of whom were diagnosed with IgAN. Only one case showed a slightly increased serum creatinine level, and no patients progressed to severe renal dysfunction.ConclusionThis study clarified the clinical features of gross hematuria after a COVID-19 vaccination. Because there was no obvious progression to severe renal dysfunction, safety of the COVID-19 vaccination is warranted at least in the protocol of inoculation twice.
| S-EPMC8590432 | biostudies-literature