Nephronophthisis and autosomal dominant tubulointerstitial kidney disease are caused by inherited genetic defects.
Symptoms, which include excessive urination and thirst, start in childhood or adolescence for nephronophthisis and in adolescence or adulthood for autosomal dominant tubulointerstitial kidney disease.
Diagnosis is based on family history as well as laboratory, imaging, and genetic tests.
Both disorders are treated by controlling consequences of kidney dysfunction; children may also require nutritional supplements and growth hormone.
Nephronophthisis and autosomal dominant tubulointerstitial kidney disease are a group of hereditary disorders that affect the development of microscopic tubules deep within the kidneys that concentrate the urine and reabsorb sodium. As a result, excessive amounts of sodium are excreted in the urine, resulting in too little sodium in the body and blood. Excessive amounts of acids may also accumulate in blood. The damaged tubules become inflamed and scarred, eventually causing chronic kidney disease severe enough to result in end-stage renal disease (ESRD, or end-stage kidney failure). Although the disorders are similar, there are some key differences, especially the inheritance pattern and the age at which chronic kidney disease becomes severe.
Nephronophthisis is inherited as an autosomal recessive disease, so one defective gene must be received from each parent. It causes symptoms that usually begin during childhood or early adolescence and usually leads to kidney failure in early adolescence.
Autosomal dominant tubulointerstitial kidney disease is inherited as an autosomal dominant disorder, so a defective gene need be inherited from only one parent for disease to occur, and it usually causes symptoms that begin in adulthood. Occasionally, the disorder occurs in a person with no family history of kidney disease. These people may have developed the gene defect as a new mutation (the gene becomes abnormal for no apparent reason) or the defect was present but not recognized in one or both parents.
A person starts to produce excessive amounts of urine and becomes excessively thirsty because the kidneys become unable to concentrate urine and conserve sodium.
In nephronophthisis, the symptoms begin in children age one year or older. Growth is slowed, and children may have weakened bones. People with nephronophthisis may have eye disorders, liver disorders, and intellectual disability (mental retardation). Later in childhood, chronic kidney disease may cause anemia, high blood pressure, nausea, and weakness.
In autosomal dominant tubulointerstitial kidney disease, the symptoms develop during adolescence or early adulthood. Excessive thirst and abnormal urine production are not as severe as in nephronophthisis. People may have high blood pressure. Other organs are not affected. Chronic kidney disease usually occurs between the ages of 30 and 70. Some people develop gout.
Family history of this type of kidney disease is an important clue to the diagnosis. Laboratory tests indicate poor kidney function, dilute urine, and possibly a low level of sodium or potassium and high level of uric acid in the blood.
Treatment includes controlling high blood pressure, anemia, and levels of sodium and uric acid in the body. Children with slowed growth may need nutritional supplements or growth hormone. Allopurinol may be given to people who develop gout. Particularly in nephronophthisis, a large daily intake of fluids and salt (sodium) is needed to compensate for the excessive excretion of sodium and the production of large volumes of dilute urine. When end-stage kidney failure occurs, chronic kidney disease develops, and dialysis or kidney transplantation may be needed.