title: Autosomal-dominant medullary cystic kidney disease type 1: clinical and molecular findings in six large Cypriot families.
abstract: BACKGROUND
  Autosomal-dominant medullary cystic kidney disease (ADMCKD), a hereditary chronic interstitial nephropathy, recently attracted attention because of the cloning or mapping of certain gene loci, namely NPHP1, NPHP2 and NPHP3 for familial juvenile nephronophthisis (NPH) and MCKD1 and MCKD2 for the adult form of medullary cystic kidney disease. Our aim was to present and discuss the clinical, biochemical, sonographic and histopathological findings in six large Cypriot families in whom molecular analysis has confirmed linkage to the MCKD1 locus on chromosome 1q21.
  
  
  METHODS
  The clinical, biochemical, sonographic and histopathological findings in 186 members of six large Cypriot families with ADMCKD-1 are presented. Creatinine clearance was calculated according to the Cockroft-Gault formula and was corrected to a body surface area (BSA) of 1.73 m2. DNA linkage analysis was performed with previously identified flanking polymorphic markers.
  
  
  RESULTS
  This disease is characterized by the absence of urinary findings in the vast majority of patients, leading to end-stage renal failure (ESRF) at a mean age of 53.7 years. Hypertension and hyperuricemia are common, especially in males, the former encountered more frequently in advanced chronic renal failure (CRF). Gout has been noted in a small percentage of male patients. Loss of urinary concentrating ability was not a prominent early feature of the disease, while severe natriuresis was observed in a few males toward ESRF. Renal cysts are mainly corticomedullary or medullary, and they are present in about 40.3% of patients and appear more frequently near ESRF.
  
  
  CONCLUSIONS
  ADMCKD type 1 is a common cause of ESRF among our dialysis population. The disease is difficult to diagnose clinically, particularly in the early stage when renal cysts are not usually present, making them a weak diagnostic finding. A dominant pattern of inheritance and DNA linkage analysis are helpful in the diagnosis of this disease.
authors.affiliation: Department of Nephrology, Ministry of Health, The Cyprus Institute of Neurology, 6 International Airport Avenue, Ayios Dhometios, 1683 Nicosia, Cyprus.
authors.forename: Christoforos
authors.initials: C
authors.lastname: Stavrou
authors.forename: Michael
authors.initials: M
authors.lastname: Koptides
authors.forename: Christos
authors.initials: C
authors.lastname: Tombazos
authors.forename: Evlalia
authors.initials: E
authors.lastname: Psara
authors.forename: Charalambos
authors.initials: C
authors.lastname: Patsias
authors.forename: Ioanna
authors.initials: I
authors.lastname: Zouvani
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Kyriacou
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: Tasos
authors.initials: T
authors.lastname: Christofides
authors.forename: Alkis
authors.initials: A
authors.lastname: Pierides
authors.forename: C Constantinou
authors.initials: CC
authors.lastname: Deltas
mesh_terms: D003535:Cyprus; D005191:Family Characteristics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics / Q000473:pathology; D033461:Hyperuricemia / Q000235:genetics / Q000473:pathology; D008297:Male; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000473:pathology; D012964:Sodium / Q000378:metabolism; D013046:Specific Gravity; D014556:Urine
chemical_list: D012964:Sodium