title: Phenotype and outcome in hereditary tubulointerstitial nephritis secondary to UMOD mutations.
abstract: BACKGROUND
  UMOD mutations cause familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are nonspecific.
  
  
  METHODS
  We reviewed cases of UMOD mutations diagnosed in the genetic laboratories of Necker Hospital (Paris, France) and of Université Catholique de Louvain (Brussels, Belgium). We also analyzed patients with MCKD/FJHN but no UMOD mutation. To determine thresholds for hyperuricemia and uric-acid excretion fraction (UAEF) according to GFR, these parameters were analyzed in 1097 patients with various renal diseases and renal function levels.
  
  
  RESULTS
  Thirty-seven distinct UMOD mutations were found in 109 patients from 45 families, all in exon 4 or 5 except for three novel mutations in exon 8. Median renal survival was 54 years. The type of mutation had a modest effect on renal survival, and intrafamilial variability was high. Detailed data available in 70 patients showed renal cysts in 24 (34.3%) of nonspecific localization in most patients. Uricemia was >75th percentile in 31 (71.4%) of 42 patients not under dialysis or allopurinol therapy. UAEF (n = 27) was <75th percentile in 70.4%. Among 136 probands with MCKD/FJHN phenotype, UMOD mutation was found in 24 (17.8%). Phenotype was not accurately predictive of UMOD mutation. Six probands had HNF1B mutations.
  
  
  CONCLUSIONS
  Hyperuricemia disproportionate to renal function represents the hallmark of renal disease caused by UMOD mutation. Renal survival is highly variable in patients with UMOD mutation. Our data also add novel insights into the interpretation of uricemia and UAEF in patients with chronic kidney diseases.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Néphrologie, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bollée
authors.forename: Karin
authors.initials: K
authors.lastname: Dahan
authors.forename: Martin
authors.initials: M
authors.lastname: Flamant
authors.forename: Vincent
authors.initials: V
authors.lastname: Morinière
authors.forename: Audrey
authors.initials: A
authors.lastname: Pawtowski
authors.forename: Laurence
authors.initials: L
authors.lastname: Heidet
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Yves
authors.initials: Y
authors.lastname: Pirson
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Bertrand
authors.initials: B
authors.lastname: Knebelmann
mesh_terms: D000328:Adult; D001530:Belgium; D015415:Biomarkers / Q000097:blood; D002493:Central Nervous System Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D003743:Dental Enamel / Q000002:abnormalities / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D006073:Gout / Q000235:genetics; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D040941:Heredity; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D052177:Kidney Diseases, Cystic / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D009154:Mutation; D009395:Nephritis, Interstitial / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010297:Paris; D010375:Pedigree; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D058949:Uromodulin / Q000235:genetics* / Q000172:deficiency; D055815:Young Adult
chemical_list: D015415:Biomarkers; C496495:HNF1B protein, human; C548612:UMOD protein, human; D058949:Uromodulin; D051539:Hepatocyte Nuclear Factor 1-beta; D014527:Uric Acid