Case of the Month #48 Nephrogenic DI

The treatment of NDI aims to remove the underlying cause wherever possible and to minimise the occurrence of Hypernatraemia and Hypovolaemia. 

 

1. Correct reversible causes: 

• Stop any drugs suspected in the aetiology  

• Correct hypokalaemia, hypercalcaemia and hypoproteinaemia 

 

2. Reduce solute load. 

• Salt intake restriction (aiming <100 mmol/day)  

• Protein intake reduction aiming to meet minimum daily requirements including essential amino acids requires specialist dietetic advice and supervision to avoid protein malnutrition. 

 

3. Diuretics – Thiazides and Amiloride.  

• Thiazides – In DI, water losses exceed solute ones causing plasma hyperosmolality and intracellular dehydration to maintain the intravascular volume. 

Thiazide diuretics cause solute loss in excess of water and reduce intravascular volume. 

This causes activation of the sympathetic nervous and renin-angiotensin-aldosterone systems and reductions in GFR and ANP.  

Less ultrafiltrate reaches the collecting duct and urine volumes can fall by up to 30%. Combined with a solute reduced diet, urine output may reduce up to 50%.  

• Amiloride may prove a useful adjunct to thiazides, causing further slight reduction in urine output and combatting thiazide-associated hypokalaemia. It may have benefit in its own right in lithium-associated nephrotoxicity. 

If administered before damage becomes irreversible, it can both reduce cellular damage and reverse the antagonism of lithium on the actions of ADH. 

 

4. NSAIDs 

PGE2 increases GFR and urine flow.  

NSAIDs reduce the formation of renal PGE2 and when used alone may reduce urine output by up to 50%. Greatest efficacy is cited for indomethacin. 

Combination with low solute diet and a thiazide diuretic may provide additional antidiuretic benefit. 

The use of NSAIDs must be weight against their side effects. 

 

5. Drugs that enhance ADH release and sensitivity (Also of benefit in CDI); Such as Chlorpropamide and Clofibrate. However, their use is limited by Hypoglycaemia and Myopathy respectively.