Isosorbide dinitrate in nephronophthisis treatment.

Area of Science:

• Pediatric Nephrology
• Medical Genetics

Background:

• Nephronophthisis is a progressive genetic disorder impacting renal tubule development, often leading to end-stage renal disease.
• It can present with isolated renal disease or extrarenal manifestations like heart defects and liver fibrosis.
• Currently, no treatments exist to slow or modify the disease's progression.

Observation:

• A patient presented neonatally with cholestatic jaundice and impaired kidney function, diagnosed with NPHP3 variants via exome sequencing.
• The patient experienced rapid clinical deterioration.
• Two agents, tolvaptan and isosorbide dinitrate, were administered to manage renal function and hypertension.

Findings:

• Tolvaptan therapy showed limited efficacy in slowing renal function decline and did not prevent the need for dialysis.
• Isosorbide dinitrate significantly improved blood pressure control, enabling the cessation of multiple antihypertensive medications.
• This marks the first report of tolvaptan and isosorbide dinitrate use in nephronophthisis.

Implications:

• Isosorbide dinitrate demonstrated a notable positive effect on blood pressure management in a patient with nephronophthisis.
• The findings suggest that isosorbide dinitrate may hold potential as a disease-modifying therapeutic agent for nephronophthisis.
• Further research is warranted to explore the therapeutic role of isosorbide dinitrate in managing nephronophthisis.