From the Guidelines
Treatment of nephrogenic diabetes insipidus (NDI) should focus on addressing the underlying cause and managing symptoms, with the primary approach involving increasing water intake and reducing urine output, as recommended by the international expert consensus statement 1. The goal of treatment is to reduce the burden of excessive urination and prevent dehydration by enhancing water reabsorption in the kidneys through alternative pathways.
- Dietary modifications, such as sodium restriction to less than 3 grams daily, can help reduce urine output by decreasing the renal osmotic load 1.
- Thiazide diuretics, such as hydrochlorothiazide at 25-50 mg twice daily, are paradoxically effective in reducing urine output by promoting sodium and water reabsorption in the proximal tubule 1.
- NSAIDs like indomethacin (25-50 mg three times daily) can be added to enhance the effect of thiazides by reducing renal blood flow and increasing water reabsorption 1.
- Amiloride (5-10 mg daily) may be beneficial in lithium-induced NDI by blocking lithium entry into collecting duct cells 1.
- For congenital X-linked NDI, a combination of hydrochlorothiazide, amiloride, and indomethacin may be necessary 1.
- Patients should be monitored for electrolyte imbalances, particularly hypokalemia with thiazide use, and potassium supplements may be needed 1.
- Regular assessment of kidney function is important, especially with long-term NSAID use, and surveillance imaging should be conducted once every 2 years to monitor for dilatation of the urinary tract and/or bladder dysfunction caused by polyuria 1. Key considerations in the management of NDI include:
- Free access to fluid in all children with NDI 1
- Normal-for-age milk intake in infants with NDI to guarantee adequate caloric intake 1
- Considering tube feeding in infants and children with repeated episodes of vomiting and dehydration and/or failure to thrive 1
- Dietetic counselling from a dietitian with experience in NDI to reduce renal osmotic load and minimize urine volume 1
- Monitoring dietary salt and protein intake to reduce renal osmotic load and minimize urine volume 1
- Starting treatment with a thiazide and prostaglandin synthesis inhibitors in symptomatic infants and children 1
- Adding amiloride to thiazide in patients with hypokalaemia induced by thiazides 1
- Evaluating treatment efficacy via urine osmolality, urine output, weight gain, and growth 1
- Ongoing drug treatment should be based on the balance of apparent efficacy and concern over development of side effects 1
From the Research
Treatment Options for Nephrogenic Diabetes Insipidus
- The treatment of nephrogenic diabetes insipidus (NDI) consists of decreasing urine output while allowing appropriate fluid balance, normonatremia, and ensuring an acceptable quality of life 2.
- Nonpharmacological interventions include sufficient water intake and a low-sodium diet 2.
- Pharmacological treatment options include thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride, used isolated or in combination 2.
Thiazide Diuretics in NDI Treatment
- Thiazide diuretics have been used in patients with NDI to decrease urine volume, but the mechanism by which it produces the paradoxical antidiuretic effect remains unclear 3.
- Hydrochlorothiazide (HCTZ) treatment has been shown to cause a significant partial recovery in aquaporin-2 (AQP2) abundance from lithium-induced downregulation 3.
- HCTZ treatment also increases the abundances of thiazide-sensitive NaCl co-transporter and alpha-epithelial sodium channel 3.
Combination Therapy for NDI
- Combination therapy with HCTZ and amiloride has been shown to be effective in treating NDI, with improved outcomes compared to HCTZ alone 4.
- This combination therapy has been well tolerated, with no severe side effects reported 4.
- HCTZ and amiloride combination therapy has also been compared to HCTZ and indomethacin combination therapy, with the former appearing to be more effective and better tolerated 4.
Mechanism of HCTZ in NDI Treatment
- The antidiuretic effect of HCTZ in NDI has been attributed to increased sodium and water uptake in proximal tubules, but alternative actions for HCTZ have been suggested 5.
- HCTZ has been shown to attenuate lithium-induced downregulation of AQP2 water channel abundance independently of the sodium-chloride cotransporter (NCC) 5.
- HCTZ treatment has also been shown to reduce lithium influx and increase AQP2 abundance on top of that of amiloride 5.