Page 12 - BH-2-1

Brain & Heart Hypochloremia in refractory heart failure

Figure 2. Hypochloromia-induced diuretic resistance and function of with-no-lysine kinases. Image created using BioRender.com.
Abbreviations: Cl: Chloride; HF: Heart failure; NCC: Na-Cl cotransporter; NKCC: Na-K-2Cl cotransporter.
that MRA therapy causes a decrease in Cl levels. 47,48 an appropriate therapy to regain Cl in refractory HF. 53,54
Acetazolamide, the carbonic anhydrase inhibitor, increases Acetazolamide exhibits a unique and critical mechanism
the concentration of Cl and decreases serum HCO of action. It acts as a non-absorbable anion, which causes
3
irrespective of serum Na. It inhibits the intracellular and the excretion of HCO in the renal tubules, exchangeable
3
luminal enzyme carbonic anhydrase in the renal proximal absorption of Cl into the blood, and simultaneous urinary
tubule. There is no evidence for the effect of treatment excretion of K. Several studies explain the potent effect of
55
with angiotensin-converting enzyme inhibitors (ACEi), this class of diuretics in specific HF situations complicated
angiotensin receptor blockers (ARBs), and beta-blockers with low serum Cl and metabolic alkalosis, which
on serum Cl metabolism. 49,50 follows the treatment with loop diuretics in the form of
refractory HF. 52,55,56
8.3. Hyperchloremia
Moreover, MRA agents are recommended for the
Hyperchloremia is typically observed in critically ill treatment of HF, but they are usually underprescribed and
patients under intensive care. Research identifies that withdrawn due to hyperkalemia. However, there is no risk of
hyperchloremia is more prevalent in subjects with acute hypochloremia associated with the use of these agents. In such
kidney injury, sepsis, and in those admitted to surgical ICUs. conditions, the use of acetazolamide, due to its K-lowering
Unlike hypochloremia, hyperchloremia is less prevalent in properties, can make the use of MRA possible. The
57
HF. It is usually iatrogenic in origin due to over-replacement correction of hypokalemia with these agents can be achieved
or loss of excessive hypotonic fluids rather than the disease by increasing the dose of MRA agents or K supplementation
process. 51 to prevent malignant ventricular arrhythmias. 45,58 In light
of these observations, the addition of acetazolamide, with
8.4. Treatment of hypochloremia or without MRA agents, to loop diuretics in patients with
Hypochloremia was recently established as an important refractory HF is a promising treatment option.
marker of HF prognosis and raised the question of diuretic
resistance. Therefore, Cl homeostasis is essential for the 8.5. A potential therapeutic target
clinical determination and treatment of HF, if necessary. Low serum Cl levels in HF and critically ill patients are
52
In the background of the “Chloride Theory” of HF, serum associated with mortality and organ dysfunction. 52,59,60 The
Cl manipulation can be an important therapeutic target. results from a cohort study of critically ill patients described
An alternative diuretic choice may be beneficial. The that both low and high serum Cl levels were associated with
addition of a carbonic anhydrase inhibitor diuretic can be acute kidney injury. More recently, two large randomized
60

Volume 2 Issue 1 (2024) 6 https://doi.org/10.36922/bh.2257