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. CONCLUSION: 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.
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. CONCLUSION: 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: Matthias T F Wolf; Bettina E Mucha; Hans C Hennies; Massimo Attanasio; Franziska Panther; Isabella Zalewski; Stephanie M Karle; Edgar A Otto; C Constantinou Deltas; Arno Fuchshuber; Friedhelm Hildebrandt Journal: Hum Genet Date: 2006-04-26 Impact factor: 4.132
Authors: Anthony J Bleyer; Stanislav Kmoch; Corinne Antignac; Vicki Robins; Kendrah Kidd; John R Kelsoe; Gerald Hladik; Philip Klemmer; Stephen J Knohl; Steven J Scheinman; Nam Vo; Ann Santi; Alese Harris; Omar Canaday; Nelson Weller; Peter J Hulick; Kristen Vogel; Frederick F Rahbari-Oskoui; Jennifer Tuazon; Constantinos Deltas; Douglas Somers; Andre Megarbane; Paul L Kimmel; C John Sperati; Avi Orr-Urtreger; Shay Ben-Shachar; David A Waugh; Stella McGinn; Anthony J Bleyer; Katerina Hodanová; Petr Vylet'al; Martina Živná; Thomas C Hart; P Suzanne Hart Journal: Clin J Am Soc Nephrol Date: 2014-02-07 Impact factor: 8.237
Authors: Kai-Uwe Eckardt; Seth L Alper; Corinne Antignac; Anthony J Bleyer; Dominique Chauveau; Karin Dahan; Constantinos Deltas; Andrew Hosking; Stanislav Kmoch; Luca Rampoldi; Michael Wiesener; Matthias T Wolf; Olivier Devuyst Journal: Kidney Int Date: 2015-03-04 Impact factor: 10.612
Authors: Thomas M F Connor; D Deren Oygar; Daniel P Gale; Retha Steenkamp; Dorothea Nitsch; Guy H Neild; Patrick H Maxwell Journal: PLoS One Date: 2013-01-17 Impact factor: 3.240