Type iv renal tubular acidosis: an emerging type of nephropathy

Abstract

Type IV renal tubular acidosis (RTA IV) is a form of hyperchloremic RTA caused by an absolute or functional hypoaldosteronism that determines a distal acidification defect by inhibiting ammoniagenesis and H+ excretion by the collecting duct. Etiology is often multifactorial and includes disorders causing a reduction in aldosterone levels or in the sensitivity of the collecting duct to the hormone. Several drugs block the renin-angiotensin system (RAS) at different steps, thus increasing the risk of developing RTA IV especially when used in association in elderly patients with diabetes, congestive heart failure, chronic renal failure, or in renal transplant recipients. Diagnosis is based on the presence of hyperkaliemia disproportionate to the degree of renal function, associated with a metabolic acidosis with normal serum anion gap and a positive urinary anion gap; urinary pH can be lower than 5.5. Some laboratory features allow differential diagnosis with distal type I RTA. The clinical impact of RTA IV is becoming progressively heavier due to the widespread use of RAS-blocking drugs in elderly patients already at risk for this complication because of their comorbidities; this situation is inducing a critical revision of the indications to association therapies with these agents. The onset of hyperkalemia in this setting poses a therapeutic dilemma, as the patients at highest risk for RTA IV are also those who can derive the strongest cardiovascular benefits from RAS pharmacological blockade. It is therefore necessary to find a balance between risks and benefits in each patient, adopting preventive measures against RTA IV.