Medullary cystic kidney disease type 2

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Classification according to ICD-10
Q61.5 Medullary cyst kidney
ICD-10 online (WHO version 2019)

The medullary cystic kidney disease type 2 , also known as MCKD2 or ADMCKD2 ( autosomal dominant medullary cystic kidney disease type 2 ) or autosomal dominant nephronophthisis called, is a very rare serious genetically caused disease of the kidney . The disease is an autosomal - dominant form of tubulointerstitial nephropathy . The MCKD2 leads to cystic kidneys at the corticomedullary border of the kidneys. The disease breaks out in adulthood and, on average, leads to terminal kidney failure in those affected in the third decade of life .

Prevalence and Genetics

Medullary cystic kidney disease type 2 is a very rare hereditary disease. The combined prevalence of type 1 and type 2 MCKD is around 1 to 9 per 1,000,000. By 2001 about 55 affected families were known to be affected by either type 1 or type 2 MCKD.

The genetic defect is located on chromosome 16 gene locus p12.3. Apparently there are mutations in the UMOD gene, it is on chromosome 16 in locus p13.11-p12.3, responsible for MCKD2.

Mutations in UMOD lead to a reduced excretion of uromodulin (Tamm-Horsfall protein) in the urine. So far, a number of UMOD mutations have been described, almost all of which are in the highly conserved exon 4.

diagnosis

As a result of the tubular concentration defect, patients with MCKD2 have considerable salt losses, which can lead to severe dehydration and electrolyte depletion. The loss of the ability to concentrate the urine to over 800 mosm * kg −1 H 2 O is an early symptom of the disease. Azotemia (above-average high levels of nitrogenous metabolic products), anemia ( anemia ), hypokalaemia (potassium deficiency) and metabolic acidosis (hyperacidity) can be detected in the blood of those affected . The impaired kidney function can be demonstrated by means of kidney function scintigraphy . The diagnosis can be made by sonography ("ultrasound") or other imaging methods such as magnetic resonance imaging .

Atrophic and cystically dilated tubules are mostly located at the corticomedullary border of the kidneys. The cysts mostly originate from the distal convolute and the collecting tubes.

Differentiation from nephronophthisis

Up until the 1970s it was assumed that nephronophthisis (NPHP1) and the two medullary-cystic kidney diseases (types 1 + 2) are the same disease. The two forms can not be distinguished histologically . The inheritance of nephronophthisis is autosomal recessive . In type 1 it leads to terminal kidney failure on average as early as the age of 13. Because of the similarity of the diseases, one also speaks of the NPH-MCKD complex .

In medullary cystic kidney disease type 2, terminal kidney failure occurs at an average age of 32 years.

therapy

To date, there is no known therapy that could stop the decline in kidney performance and even chronic kidney failure. The treatment of MCKD2 is therefore purely symptomatic. The only cure is a kidney transplant . With terminal failure of the kidneys, renal replacement therapy becomes necessary. Either in the form of dialysis or by means of kidney transplantation.

In addition to impaired kidney function, hyperuricemia and gout are also associated with the disease.

Individual evidence

  1. ↑ orpha.net: Kidney disease, medullary cystic, autosomal dominant, with or without hyperuricemia, viewed on October 4, 2008.
  2. ^ A. Amoroso: Autosomal Dominant Medullary Cystic Kidney Disease In: Orphanet encyclopedia June 2001.
  3. ↑ F. Scolari et al: Identification of a new locus for medullary cystic disease, on chromosome 16p12. In: Am. J. Hum. Genet. 64, 1999, pp. 1655-1660. PMID 10330352
  4. ↑ TC Hart et al: Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. In: J. Med. Genet. 39, 2002, pp. 882-892. PMID 12471200 .
  5. ↑ K. Dahan et al .: A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin. In: J Am Soc Nephrol 14, 2003, pp. 2883-2893. PMID 14569098
  6. ^ XM Lens et al .: A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease. In: Am J Kidney Dis 46, 2005, pp. 52-57. PMID 15983957
  7. ↑ H. Hecht et al .: Poor renal uptake of 99mtechnetiumdimercaptosuccinic acid and near normal 99mtechnetiummercaptoacetyltriglycine renogram in nephronophthisis. In: Pediatr Nephrol 10, 1996, pp. 167-170.
  8. ↑ RC Pabico et al: Renal tubular dysfunction in patients with cystic disease of the kidneys. In: Urology 51, 1998, pp. 156-160.
  9. ↑ a b c d F. Hildebrandt et al.: Nephronophthisis and related diseases. (PDF; 85 kB) In: medgen 12, 2000, pp. 225-231.
  10. ^ BC Chamberlin et al.: Juvenile nephronophthisis and medullary cystic disease. In: Mayo Clin. Proc. 52, 1977, pp. 485-491. PMID 881899 .
  11. ↑ R. Waldherr u. .a: The nephronophthisis complex: a clinicopathologic study in children. In: Virchows Arch Pathol Anat 394, 1982, pp. 235-254.

literature

Web links