Care by a nephrologist is recommended.
Childhood/Adolescent-Onset Disease Only
Anemia may be reversed by treatment with erythropoietin [Zivná et al 2009], a medication that is given subcutaneously and managed by hematologists or pediatric nephrologists. Dose is based on response to therapy. No clear target dose has been established to date; dosage is left to the discretion of the hematologist or nephrologist.
Many children have relatively mild anemia with hemoglobin levels of 10-11 g/dL, and can be safely followed off erythropoietin.
Note: The dose of erythropoietin will need to be reduced as hemoglobin concentration increases during adolescence.
Iron stores should be replenished as needed to treat iron deficiency (an unrelated condition) if it is present.
Mild hypotension, hyperkalemia, and acidemia. Fludrocortisone, a synthetic analog of aldosterone, has been used for many years as a form of aldosterone replacement. In individuals with childhood/adolescent-onset ADTKD-REN, fludrocortisone corrects aldosterone deficiency and associated mild hypotension, as well as serum levels of urate, potassium, and bicarbonate.
In a retrospective cohort study [Živná et al 2020], treatment of acidosis with sodium bicarbonate was often suboptimal (i.e., treated serum bicarbonate levels <24 mEq/L); whereas individuals receiving fludrocortisone were more likely to have a serum bicarbonate level >24 mEq/L. Another consideration is that the small dose of the fludrocortisone pill (0.1 mg) vs the higher dose required for sodium bicarbonate (often >1300 mg/day) is favorable, especially for children.
Because fludrocortisone increases estimated glomerular filtration rate (eGFR), fludrocortisone treatment should be started prior to chronic kidney disease (CKD) Stage 3 (eGFR >60 mL/min/1.73 m2). Note: When eGFR is <60 mL/min/1.73 m2, fluid retention and hypertension may develop from fludrocortisone [Author, personal observation].
Hypotension is usually asymptomatic but will respond to a dietary sodium intake of 3-4 g/day, administration of sodium bicarbonate tablets, or the use of fludrocortisone.
Acidosis can be treated with sodium bicarbonate tablets or sodium citrate in a liquid formulation, dosed based on body size and degree of acidemia; however, Živná et al [2020] found that treatment of acidemia with sodium bicarbonate was often suboptimal.
Hyperkalemia responds to dietary potassium restriction; administration of sodium bicarbonate will also lower serum potassium.
Risk of acute kidney injury. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in a febrile child with ADTKD-REN precipitated acute renal failure [Bleyer et al 2010b]. The use of other analgesics/antipyretics should be considered.
Both Childhood/Adolescent-Onset and Adult-Onset Disease
Hyperuricemia/gout. Prevention of gout attacks with allopurinol should be considered in individuals with gout. With allopurinol treatment, serum uric acid concentration returns to normal and gout attacks can be entirely prevented. Lifelong therapy with allopurinol is required for future gout prevention.
Acute gout typically responds well to prednisone or colchicine. Prednisone is preferred to nonsteroidal anti-inflammatory drugs because the combination of NSAIDs and the low renin state in individuals with ADTKD-REN can lead to acute kidney injury.
For individuals with allergies or intolerance to allopurinol, febuxostat may be considered.
Kidney disease. Refer to a nephrologist to monitor kidney function, evaluate for manifestations of chronic kidney disease, and prepare for renal replacement therapy when ESKD occurs. Note: Affected individuals should not be on the low-sodium diet typically used in the treatment of CKD.
Renal replacement therapies such as hemodialysis and peritoneal dialysis replace renal function but are associated with potential complications.
Kidney transplantation cures ADTKD-REN, as the transplanted kidney does not develop the disease.