Tubulopathies

Definition, Etiology, Clinical FeaturesTop

Tubulopathy is an umbrella term that encompasses various disease processes affecting the renal tubules. Some of these include renal tubular acidosis (RTA) (with distal RTA aka type 1, proximal RTA aka type 2, and hypoaldosteronism aka type 4), tubular channel defects leading to salt-losing nephropathies, and nephrogenic diabetes insipidus. The vast majority of these diseases in adults are acquired as a result of another disease process damaging the renal tubules, and very rarely the etiology is genetic or inherited.

Tubulopathies can present in a variety of ways, ranging from an asymptomatic incidental diagnosis to severe acidosis and abnormal potassium levels.

Clinicians often consider RTA when a non–anion gap metabolic acidosis (NAGMA) is discovered in a patient with other electrolyte derangements and normal renal function or when the acidosis is found to be out of proportion to the degree of renal function.

RTA is characterized by tubular inability to maintain acid-base balance despite relatively well-preserved renal function. This can be due to either net bicarbonate loss (proximal RTA) or inability to excrete acid (distal RTA).

DiagnosisTop

RTA is usually suspected following the establishment of a hyperchloremic NAGMA. Diagnosis requires measurement of urinary pH and urinary anion gap (UAG), along with urinary osmolar gap (UOG) to estimate urinary ammonium excretion. In a patient with chronic NAGMA, a low urinary ammonium excretion, indicated by a positive UAG or relatively low UOG (<150 mOsm/kg), helps distinguish RTA (predominantly distal) from other causes of NAGMA, such as diarrhea.

UAG (in mEq/L or mmol/L) = urine sodium + urine potassium – urine chloride

UOG* = 2 × (urine sodium + urine potassium) + urine urea + urine glucose

* For all components in mmol/L.