It typically occurs sporadically secondary to impairment in the renin - aldosterone - renal tubule axis (hyporeninemic hypoaldosteronism), which occurs in patients with the following: Diabetic nephropathy Chronic interstitial nephritis Other factors that can contribute to type 4 RTA include the following: ACE inhibitor use Aldosterone synthase type I or II deficiency Angiotensin II receptor blocker use Chronic kidney disease, usually due to diabetic nephropathy or chronic interstitial nephritis Congenital adrenal hyperplasia, particularly 21-hydroxylase deficiency Critical illness Cyclosporine use Heparin use (including low molecular weight heparins) HIV nephropathy (due, possibly in part, to infection with Mycobacterium avium complex or cytomegalovirus) Interstitial renal damage (eg, due to systemic lupus erythematosus, obstructive uropathy, or sickle cell disease) Nonsteroidal anti-inflammatory drugs (NSAIDs) Obstructive uropathy Other drugs (eg, pentamidine, trimethoprim) Potassium-sparing diuretics (eg, amiloride, eplerenone, spironolactone, triamterene) Primary adrenal insufficiency Pseudohypoaldosteronism (type I or II) Volume expansion (eg, in acute glomerulonephritis or chronic kidney disease) Symptoms and Signs of RTA RTA is usually asymptomatic.