Nephronophthisis

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Classification according to ICD-10
N11.8 Other chronic tubulointerstitial nephritis
ICD-10 online (WHO version 2019)

Nephronophthisis (nephrotoxicity νεφρός of gr, kidney;. Phthisis of gr φθίσις, loss.) Is the name for a group of rare serious genetically -related diseases of the kidney . The disease is an autosomal - recessive form of tubulointerstitial nephritis . Nephronophthisis leads to cystic kidneys at the corticomedullary border of the kidneys. So far, six different genes are known in which mutations or deletions can lead to nephronophthisis. The most common is familial juvenile nephronophthisis (NPHP1).

Prevalence

Nephronophthisis is a rare hereditary disease. The prevalence of all six disease types together is around 1: 100,000. However, the information in the literature varies considerably. This is because, on the one hand, the disease is quite rare and, on the other hand, it is difficult to diagnose. There are estimates for the United States that there are 9 people for every 8.3 million live births. In contrast, the estimates for Canada for live births are 1: 50,000. Male and female patients are equally affected by the disease.

Despite the relatively low incidence of nephronophthisis, the latter is the most common genetic cause of terminal kidney failure in the first three decades of life.

Juvenile Nephronophthisis (NPHP1)

The NPHP1 gene responsible for juvenile nephronophthisis is located on chromosome 2 gene locus q13 in humans . Mutations or a gene deletion can lead to an extensive loss of function of the protein nephrocystin-1, which is encoded from the NPHP1 gene .

The first symptoms of the disease are shown by polyuria (abnormally increased urine excretion) which usually occurs between the ages of 4 and 6. The affected children stand out due to their excessive need for fluids at night ( polydipsia , pathologically increased thirst). Since the symptoms are not very pronounced, the disease is usually only diagnosed at a very advanced stage of chronic kidney failure . At the mean age of 13 years, terminal kidney failure occurs, which all patients up to the age of 25 reach.

Infantile Nephronophthisis (NPHP2)

The NPHP2 gene responsible for the disease is located in humans on chromosome 9 gene locus q22-q31. Mutations or a gene deletion can lead to an extensive loss of function of the protein inversin encoded by the NPHP2 gene . Terminal kidney failure in type 2 nephronophthisis usually occurs before the first year of life, often prenatally (before birth).

Adolescent Nephronophthisis (NPHP3)

The adolescent nephronophthisis has its origin on chromosome 3 gene locus q21-q22. Terminal kidney failure occurs on average at the age of 19, which is the case significantly later compared to NPHP1 and NPHP2.

NPHP4, NPHP5, NPHP6, NPHP7

Little is known about these four forms of nephronophthisis. Type 4 nephronophthisis originates from chromosome 1 gene locus p36.22. The NPHP4 gene codes for the protein nephroretinin . The NPHP5 gene, also called IQCB1, is located on chromosome 3 gene locus q21.1 and codes for nephrocystin-5. NPHP6, also called CEP290, is located on chromosome 12 gene locus q21.33. The “NPHP7 gene”, which was only discovered in 2007, is the GLIS2 gene and codes for the zinc finger protein GLIS2.

diagnosis

Patients with nephronophthisis have significant salt losses as a result of the tubular concentration defect, which can lead to severe dehydration and electrolyte changes. 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 levels of nitrogenous metabolic products), anemia ( anemia ), hypokalemia (potassium deficiency) and metabolic acidosis (over- acidosis ) can be detected in the blood of those affected .

The impaired kidney function can be monitored with the glomerular filtration rate (GFR), which decreases over time . A side-by-side determination of the GFR is also possible with kidney function scintigraphy . The diagnosis can be made by sonography ("ultrasound") or other imaging methods , such as magnetic resonance tomography .

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 medullary cystic kidney diseases

Up until the 1970s it was assumed that nephronophthisis 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 , while it is autosomal dominant in MCKD1 and MCKD2. Because of the similarity of the diseases, one also speaks of the NPH-MCKD complex .

therapy

To date, there is no known therapy that could stop the decline in kidney performance and even chronic kidney failure . Treatment of nephronophthisis is therefore purely symptomatic. The only cure is a kidney transplant . With the 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 medullary cystic kidney disease.

See also

Individual evidence

  1. ↑ orpha.net: Kidney disease, medullary cystic, autosomal recessive viewed October 4, 2008.
  2. ↑ DE Potter et al .: Treatment of end-stage renal disease in children: A 15-year experiance. In: Kidney Int . 18, 1980, pp. 103-109. PMID
  3. ↑ R. Waldherr among others: The Nephronophthis complex. In: Kidney and high pressure diseases 12, 1983, pp. 397-406.
  4. ↑ T. Vetsi: Deletion and breakpoint analysis by means of the Southern blot method in families with type 1 nephronophthisis (NPH1). (PDF; 1.0 MB) Dissertation, Albert-Ludwigs-Universität Freiburg im Breisgau, 2003.
  5. ↑ M. Attanasio et al .: Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. In: Nature Genet 39, 2007, pp. 1018-1024. PMID 17618285
  6. ↑ a b c d e f g F. Hildebrandt et al.: Nephronophthisis and related diseases. (PDF; 85 kB) In: medgen 12, 2000, pp. 225-231.
  7. ↑ F. Hildebrandt et al.: Molecular genetic identification of families with juvenile nephronophthisis type 1: rate of progression to renal failure. In: Kidney Int 51, 1997, pp. 261-269.
  8. ↑ H. Omran et al .: Identification of a new gene locus for adolescent nephronophthisis on chromosome 3q22 in a large venezuelan pedigree. In: Am. J. Hum. Genet. 66, 2000, pp. 118-127. PMID
  9. ↑ 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.
  10. ↑ RC Pabico et al: Renal tubular dysfunction in patients with cystic disease of the kidneys. In: Urology. 51, 1998, pp. 156-160.
  11. ^ BC Chamberlin et al.: Juvenile nephronophthisis and medullary cystic disease. In: Mayo Clin. Proc. 52, 1977, pp. 485-491. PMID 881899 .

literature

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