Autosomal dominant tubulointerstitial kidney disease

BACKGROUND: Heterozygous mutations in the gene encoding renin (REN) cause autosomal dominant tubulointerstitial kidney disease (ADTKD), early-onset anaemia and hyperuricaemia; only four different mutations have been described in the published literature to date. We report a novel dominant REN mutation discovered in an individual after forty years of renal disease. CASE PRESENTATION: A 57 year old Caucasian woman with chronic kidney disease stage five was reviewed in a regional joint renal genetics clinic...

Mucin 1 kidney disease, previously referred to as medullary cystic kidney disease type 1, is a rare hereditary kidney disease. It is one of several diseases now termed autosomal dominant tubulointerstitial kidney disease, as proposed by a KDIGO (Kidney Disease: Improving Global Outcomes) consensus report in 2014. Autosomal dominant tubulointerstitial kidney diseases share common clinical findings, such as autosomal dominant inheritance, bland urinary sediment, absent to mild proteinuria, and progressive loss of kidney function...

INTRODUCTION: Medullary cystic kidney disease type 1 (MCKD1; OMIM #174000) is a familial progressive tubule-interstitial nephropathy belonging to the recently defined group of autosomal dominant tubulointerstitial kidney diseases (ADTKD). CASE REPORT: A specific type of cytosine insertion in the extracellular variable number tandem repeat (VNTR) domain of the MUC1 gene causing the disease was tested in a group of 21 families with ADTKD. We identified this type of MUC1 mutation in two families, whose affected members are described in detail in this case report...

Familial juvenile hyperuricaemic nephropathy (FJHN) is a diagnosis that is easily missed. It has taken a long time to clarify the pathophysiology and prevalence of this disease entity which has been shown to be genetically identical to medullary cystic kidney disease (MCKD) type II. The initial suspicion that uric acid was the noxious agent has been replaced by the recognition that a mutant uromodulin (UMOD) is the real culprit-although the exact mechanisms of pathogenicity remain uncertain. The mutation has been traced to the UMOD gene in chromosome 16...

BACKGROUND: Uromodulin (UMOD)-associated kidney disease belongs to the group of autosomal dominant interstitial kidney diseases and is caused by mutations in the UMOD gene. Affected patients present with hyperuricemia, gout, and progressive renal failure. The disease is thought to be very rare but is probably underdiagnosed. METHODS: Two index patients from two families with tubulointerstitial nephropathy and hyperuricemia were examined, including blood and urine chemistry, ultrasound, and mutation analysis of the UMOD gene...

BACKGROUND: Uromodulin kidney disease (UKD) is an inherited kidney disease caused by a uromodulin (UMOD) gene mutation. The UMOD gene encodes the Tamm-Horsfall protein (THP), which is the most abundant protein in healthy human urine. Because of its rarity, the incidence of UKD has not been fully elucidated. The purpose of the present study is to clarify the frequency of UKD among patients who underwent renal biopsy. METHODS: Immunostaining for THP was performed for patients <50 years of age with renal insufficiency and hyperuricemia without overt urinalysis abnormality from renal biopsy databases...

BACKGROUND: UMOD mutations cause familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease (MCKD), although these phenotypes are nonspecific. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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...

We report the case of a Japanese family suffering from familial juvenile hyperuricemic nephropathy (FJHN) due to a rare missense mutation of the uromodulin (UMOD) gene. An 18-year-old male presented with gout, hyperuricemia, and stage 3 chronic kidney disease. Mostly, FJHN is caused by a mutation altering the cystine residue of UMOD/Tamm-Horsfall protein. However, in the present case, a T688C mutation was identified in exon 4, resulting in amino acid substitution with arginine replacing tryptophan at position 230 (Trp230Arg)...

Familial juvenile hyperuricemic nephropathy (FJHN; OMIM 162000) is an autosomal dominant disorder characterized by hyperuricemia and gouty arthritis due to reduced kidney excretion of uric acid and progressive renal failure. Gradual progressive interstitial renal disease, with basement membrane thickening and glomerulosclerosis resulting from fibrosis, starts in early life. In most cases of FJHN, uromodulin gene (UMOD) is responsible for the disease; however, there has been only one report of a genetically confirmed FJHN family in Korea...

The most abundant urinary protein, Tamm-Horsfall protein, later renamed uromodulin, is expressed exclusively by the thick ascending limb cells of the kidney and released into urine from the apical cell membrane. Uromodulin is believed to protect against urinary tract infections and stones, but its other physiologic functions have remained obscure until recently. Renewed interest in uromodulin has been brought about by the identification of uromodulin mutations as causes of a discrete group of diseases that are distinct from nephronophthisis...

Autosomal dominant tubulointerstitial kidney disease is characterized by the poorly recognized inheritance of slowly progressive renal failure leading to ESRD in later life. Patients with this condition have bland urinary sediment, and renal ultrasound typically reveals normal to small kidneys, with occasional individuals having small medullary cysts. Diagnosis relies on the clinical acumen of the nephrologist. Obtaining a thorough family history and records of affected family members is especially helpful...

Mutations in the UMOD gene coding for uromodulin cause autosomal dominant tubulointerstitial kidney disease. Uromodulin is known to regulate transport processes in the thick ascending limb, but it remains unknown whether UMOD mutations are associated with functional tubular alterations in the early phase of the disease. The responses to furosemide and to a water deprivation test were compared in a 32-year-old female patient carrying the pathogenic UMOD mutation p.C217G and her unaffected 31-year-old sister...

Autosomal dominant tubulointerstitial kidney disease (ADTKD) refers to a group of conditions characterized by autosomal dominant inheritance, a bland urinary sediment with minimal blood and protein, pathologic changes of tubular and interstitial fibrosis, and slowly progressive chronic kidney disease. This commentary discusses recent advances in our medical knowledge of these conditions, including the recent identification of mutations in the MUC1 gene as a cause of ADTKD and changes in terminology proposed by Ekici et al...