(See also Overview of Cystic Kidney Disease Overview of Cystic Kidney Disease Cystic kidney disease may be congenital or acquired. Congenital disorders may be inherited as autosomal dominant disorders or autosomal recessive disorders or have other causes (eg, sporadic... read more .)
Nephronophthisis and autosomal dominant tubulointerstitial kidney disease (ADTKD) are grouped together because they share many features. Pathologically, they can cause cysts restricted to the renal medulla or corticomedullary border, as well as a triad of tubular atrophy, tubular basement membrane disintegration, and interstitial fibrosis. Cysts may or may not be present and are a result of tubular dilation. They probably share similar mechanisms, although these are not well characterized. Features of both disorders include the following:
A vasopressin (ADH)-resistant urine-concentrating defect that leads to polyuria and polydipsia
Sodium wasting severe enough to require supplementation
Anemia
Metabolic acidosis
A tendency toward mild proteinuria and a benign urinary sediment
Eventually, ESKD
Key differences between nephronophthisis and medullary cystic kidney disease include inheritance patterns and age at onset of chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more 
.
Nephronophthisis
Inheritance is autosomal recessive. Nephronophthisis accounts for up to 15% of chronic kidney disease with renal failure in children and young adults (< 20 years). There are 3 types:
Infantile, median age at onset 1 year
Juvenile, median age at onset 13 years
Adolescent, median age at onset 19 years
Eleven gene mutations have been identified in patients with nephronophthisis. Mutations of the NPHP1 gene are the most common, identified in about 30 to 60% of patients. About 10% of patients with nephronophthisis also have other manifestations, including retinitis pigmentosa, hepatic fibrosis Hepatic Fibrosis Hepatic fibrosis is overly exuberant wound healing in which excessive connective tissue builds up in the liver. The extracellular matrix is overproduced, degraded deficiently, or both. The trigger... read more , intellectual disability, and other neurologic abnormalities.
End-stage kidney disease (ESKD) often develops during childhood and causes growth restriction and bone disease. However, in many patients, these problems develop slowly over years and are so well compensated for that they are not recognized as abnormal until significant uremic symptoms Symptoms and Signs Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more appear. Hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more 
sometimes develops.
Diagnosis of Nephronophthisis
Imaging, genetic testing, or both
The diagnosis should be suspected in children with the following, particularly if the urinary sediment is benign:
Polydipsia and polyuria
Progressively decreasing renal function, particularly without hypertension
Associated extrarenal findings
Anemia out of proportion to the degree of renal failure
Proteinuria is usually absent. Diagnosis is confirmed by imaging, but cysts often occur only late in disease. Ultrasonography, CT, or MRI may show smooth renal outlines with normal-sized or small kidneys, loss of corticomedullary differentiation, and multiple cysts at the corticomedullary junction. Hydronephrosis is typically absent. Genetic testing is available.
Treatment of Nephronophthisis
Supportive care
In early disease, treatment involves management of hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more , electrolyte abnormalities and acid-base disorders Acid-Base Disorders Acid-base disorders are pathologic changes in carbon dioxide partial pressure (Pco2) or serum bicarbonate (HCO3−) that typically produce abnormal arterial pH values. Acidemia is serum... read more , and anemia Overview of Decreased Erythropoiesis Anemia, a decrease in the number of red blood cells (RBCs), hemoglobin (Hb) content, or hematocrit (Hct), can result from decreased RBC production (erythropoiesis), increased RBC destruction... read more . Children with growth restriction may respond to nutritional supplements and growth hormone therapy. Ultimately, all patients develop chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more and require dialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more or transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more .
Autosomal dominant tubulointerstitial kidney disease (ADTKD)
Autosomal dominant tubulointerstitial kidney disease (previously known as medullary cystic kidney disease) is a group of uncommon genetic disorders. A consensus report (1 Treatment reference Nephronophthisis and autosomal dominant tubulointerstitial kidney disease (ADTKD) are inherited disorders that cause cysts restricted to the renal medulla or corticomedullary border and, eventually... read more ) from Kidney Disease Improving Global Outcomes (KDIGO) has proposed classifying these disorders based on the causative gene, of which 4 are currently known (see table ).
Histopathologic changes common to these disorders include
Interstitial fibrosis
Tubular atrophy
Thickening of tubular basement membranes
Possible cyst formation as a result of tubular dilation
Absence of complement and immunoglobulin staining on immunofluorescence
Autosomal dominant tubulointerstitial kidney disease affects people in their 30s through 70s. About 15% of patients have no family history, suggesting a sporadic new mutation. Hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more is common but usually only modest and typically does not precede the onset of kidney dysfunction. Hyperuricemia and gout is common and can precede the onset of significant renal insufficiency. End-stage kidney disease (ESKD) typically develops at age 30 to 50. ADTKD should be suspected in patients with the following, particularly if the urinary sediment is benign:
Polydipsia and polyuria
Gout at a young age
Proteinuria is absent to mild. Results of imaging studies have many similarities to that of nephronophthisis; however, renal medullary cysts are only sometimes visible. Genetic testing can confirm the diagnosis. Kidney biopsy Renal biopsy Biopsy of the urinary tract requires a trained specialist (nephrologist, urologist, or interventional radiologist). Indications for diagnostic biopsy include unexplained nephritic or nephrotic... read more may be necessary in at least one affected family member.
Treatment is generally similar to treatment of nephronophthisis Treatment Nephronophthisis and autosomal dominant tubulointerstitial kidney disease (ADTKD) are inherited disorders that cause cysts restricted to the renal medulla or corticomedullary border and, eventually... read more . Allopurinol can help control gout.
Treatment reference
1. Eckardt K-U, Alper SL, Antignac C, et al: Autosomal dominant tubulointerstitial kidney disease: Diagnosis, classification, and management—A KDIGO consensus report. Kidney Int 88(4):676-683, 2015. doi: 10.1038/ki.2015.28
Key Points
Nephronophthisis and autosomal dominant tubulointerstitial kidney disease cause inability to concentrate urine (with polydipsia and polyuria), sodium wasting, anemia, and ESKD.
Nephronophthisis is autosomal recessive and causes ESKD during childhood, whereas ADTKD is autosomal dominant and causes ESKD at age 30 to 50.
Obtain renal imaging and, when available, genetic testing.
Treat associated disorders and treat kidney disease supportively.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
allopurinol |
Aloprim, Zyloprim |
