Autosomal dominant tubulointerstitial kidney disease due to REN mutations

Other Names: FJHN type 2; REN-associated familial juvenile hyperuricemic nephropathy; REN-associated kidney disease; Familial juvenile hyperuricemic nephropathy type 2; REN-associated kidney disease); ADTKD-REN; REN-associated FJHN; Hyperuricemic nephropathy, familial juvenile 2; ADTKD due to REN mutations; Autosomal dominant tubulointerstitial kidney disease, REN-related

Autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN) is an inherited disorder that causes anemia, mildly low blood pressure, and an increased chance to develop kidney failure in childhood. In the teenage years, patients may develop a painful type of arthritis called gout. As an adult, the anemia improves but patients develop slowly progressive chronic kidney disease, which may lead to the need for dialysis or kidney transplantation between 40 and 80 years of age.

Epidemiology

Autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN) is very rare, with less than 20 families reported worldwide.

Cause

ADTKD-REN is caused by a mistake (mutation) in one copy of the REN gene. This mistake leads to a decreased production of normal renin and the deposition of abnormal renin in kidney cells, leading to slow loss of kidney function.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN) is inherited in an autosomal dominant pattern. All individuals inherit two copies of each gene. In autosomal dominant conditions, having a mutation in just one copy of the REN gene causes the person to have the disease. Some people are born with an autosomal dominant condition due to a new genetic mutation (de novo) and do not have a history of this condition in their family. There is nothing either parent can do, before or during pregnancy, to cause a child to have this.

Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the REN mutation and ADTKD-REN. Children who inherit the REN mutation will have ADTKD-REN. They may be more or less severely affected than their parent.

Signs and symptoms

The symptoms of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN) are age-dependent. In childhood, patients may have anemia, low blood pressure and mildly high blood levels of potassium, uric acid, and creatinine. When young individuals with ADTKD-REN develop a fever or viral illness and are treated with a medication like ibuprofen, they may develop a sudden (acute) decrease in kidney function. Medical treatment will result in a return of kidney function to its prior levels. In the teenage years, patients may develop gout, a painful arthritis (joint inflammation) that often occurs in the big toe, ankle, or knee. In adulthood, worsening kidney function may lead to the need for dialysis between ages 40 and 80.

Diagnosis

Diagnosis is based on findings of hypoproliferative anemia (low reticulocyte count relative to hemoglobin concentration and low erythropoietin concentration), hyperuricemia (serum uric acid concentration >6 mg/dL), decreased fractional excretion of urinary uric acid, bland urinary sediment, and low plasma renin activity. Kidney size is normal or small with no evidence of cyst formation. REN (encoding renin) is the only gene in which mutation is known to cause ADTKD-REN.

Treatment

Treatment for autosomal dominant tubule-interstitial kidney disease due to REN mutations (ADTKD-REN) is based on managing the symptoms. The medication erythropoietin is very effective in treating the anemia that occurs in childhood. Gout can also be prevented with medications such as allopurinol or febuxostat. Fludrocortisone has been shown to improve low blood pressure and high potassium levels in ADTKD-REN and theoretically may slow progression of ADTKD-REN. Eventually, patients may need a kidney transplant or dialysis. Live donor kidney transplantation is the optimal treatment for worsening kidney disease, and patients who undergo kidney transplant for this condition do extremely well. The condition does not come back in the transplanted kidney.

Prognosis

The long-term outlook for people with autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN) is good, though patients will often need a kidney transplant or start dialysis between the ages of 40 and 80. At this point, it is difficult to predict at what age patients will develop end-stage kidney failure.

NIH genetic and rare disease info

• NIH info on Autosomal dominant tubulointerstitial kidney disease due to REN mutations

Autosomal dominant tubulointerstitial kidney disease due to REN mutations is a rare disease.

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