Acid–Base Imbalance in Pseudohypoaldosteronism Type 1 in Comparison With Type IV Renal Tubular Acidosis

Abstract

Context Pseudohypoaldosteronism (PHA) type 1 (PHA1) has been treated as a genetic variant of type IV renal tubular acidosis (RTA), leading to the conception that PHA1 develops hyperchloremic acidosis with a normal anion gap (AG). Objective To delineate the acid-base imbalance in PHA1A (dominant type) and PHA1B (recessive type). Design We conducted the following: 1) a retrospective chart review of our patient with PHA1B, and 2) a literature search of PHA1 cases focusing on acid-base balance. Main Outcome Measures The incidence and nature of acidosis, including chloride levels and AG. Results In our patient with PHA1B, seven salt-wasting episodes were analyzed. Acidosis was ascertained each time, and accompanied by hypochloremia except in one episode. AG was elevated in five episodes, while hyperlacticaemia was present in three. In the literature, 41 cases of PHA1A and 65 cases of PHA1B have been identified. During salt-wasting crises, acidosis developed in 85% of PHA1A cases and 87% of PHA1B cases. Hypochloremia was present in 69% of PHA1A cases with available data (n = 13) and 54% of eligible PHA1B cases (n = 13), with mean chloride levels of 96 mEq/L and 95 mEq/L, respectively. Increased AG was less frequently reported (14% in PHA1A and 44% in PHA1B). Conclusions Patients with PHA1 frequently presented with metabolic acidosis. However, hyperchloremia may not be a universal finding, whereas hypochloremia and increased AG may occur in a substantial proportion of the patients.

Classification of pseudohypoaldosteronism type II as type IV renal tubular acidosis: results of a literature review

“…In contrast to the present results, our previous study on PHA1 found that the phenotype was inconsistent with typical hyperchloremic type IV RTA [22]; analysis of data related to seven times well-documented salt-wasting crises experienced by our PHA1B patient between 3 and Endocrine Journal Advance Publication 7 years of age revealed that most of the crises were accompanied by hypochloremia and elevated AG levels. In addition, analysis of 106 PHA1 cases collected through a literature search found that hypochloremia was present in 69% (9 of 13) of PHA1A and 54% (7 of 13) of PHA1B cases at the time of salt-wasting.…”

“…This fundamental difference in Na + kinetics will cause the opposite direction in the chloride levels between PHA1 (hypochloremic) and PHA2 (hyperchloremic). As we speculate before, an elevated AG found in PHA1 may derive from hyperlacticemia caused by severe volume depletion [22]. Considering that aldosterone unresponsiveness is not the main factor in the pathogenesis of PHA2, it may be thoughtful to treat PHA1 and PHA2 as completely different entities, despite their nomenclature.…”

“…Recently, we found that the nature of acidosis in PHA1 was not always identical to that in type IV RTA; hypochloremia, not hyperchloremia, and increased AG were found in a substantial portion of the patients with PHA1 [22]. In this study, we conducted an extensive literature search focusing on the acid-base imbalance in PHA2 and attempted to verify the concept that PHA2 presents with type IV RTA.…”

“…We defined normal Cllevels those within the range 98-108 mEq/L, which corresponds to 2 standard deviations (SD) of the mean data obtained from 29,490 adult patients with normal renal function and electrolyte levels [24]. The definition of acidosis was arbitrarily set as either a pH value lower than 7.30 or a bicarbonate (HCO3 -) level lower than 20 mEq/L [22]. AG was calculated using the following equation: AG…”

The TMEM16A channel as a potential therapeutic target in vascular disease

“…Hypochloraemia ([Cl − ] e < 96 mM) is observed in patients with chronic cardiac failure and is associated with higher risk of mortality in patients with acute or chronic heart failure [32,33,34,35]. Hyperchloremia ([Cl − ] e > 110 mM), which accompanies a range of kidney disturbances, is an independent predictor for hypertension [36,37], and positively associated with increased mortality rate of hospitalised patients [34]. These conditions are expected to impact E Cl and thus the magnitude of TMEM16A currents.…”