Diuretic-induced hypokalaemia: an updated review

Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%–56% of hypokalaemia in patients taking thiazide diuretics. The clinical manifestations of hypokalaemia due to diuretics are non-specific, varying from asymptomatic to fatal arrhythmia. Diagnosis of hypokalaemia is based on the level of serum potassium. ECG is useful in identifying the more severe consequences. A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac arrhythmias can increase the risk of cardiovascular events and mortality. Thiazide-induced potassium depletion may cause dysglycaemia. The risk of thiazide-induced hypokalaemia is higher in women and in black people. Reducing diuretic dose and potassium supplementation are the most direct and effective therapies for hypokalaemia. Combining with a potassium-sparing diuretic or blocker of the renin–angiotensin system also reduces the risk of hypokalaemia. Lowering salt intake and increasing intake of vegetables and fruits help to reduce blood pressure as well as prevent hypokalaemia.

Patient with Bartter syndrome in whom chronic potassium depletion was considered one of the causes of hyponatremia

A 53-year-old man was admitted to our hospital because of general fatigue and disorientation. He had been diagnosed with Bartter syndrome in his teens and had been taking potassium preparations since then. However, his serum potassium concentration (K+s) remained persistently low. Ten days before admission, he developed fever. He was diagnosed as having bronchitis and was treated with antibiotics. Although his fever subsided, general fatigue worsened. Laboratory examination showed hyponatraemia (127 mEq/L), while K+s was 2.3 mEq/L. C reactive protein was negative. On admission, laboratory examination revealed deterioration of hyponatraemia (125 mEq/L). Although his serum sodium concentration (Na+s) was refractory to electrolyte replacement, the level increased towards normal after spironolactone administration, following normalisation of K+s, suggesting that hyponatraemia was caused by K+ depletion. Physicians should be aware of the importance of the effects of exchangeable K+ (K+e) on Na+s.

Abstract P003: Kidney-specific Knockout Of The Clock Protein Bmal1 Is Protective In Salt-sensitive Hypertension

Intro: Circadian clock factors, such as BMAL1, influence systemic blood pressure (BP) control. Previously, we generated renal distal segment BMAL1 knockout mice (KS-BMAL1 KO) that exhibit lower BP compared to control mice (CNTL) in males but not females. Additionally, male KS-BMAL1 KO retain less sodium following potassium depletion compared to CNTL, a difference not seen in females. Goal: The goal of this study was to test the hypothesis that male KS-BMAL1 KO display lower BP than CNTL in response to a potassium deficient, high salt diet. Methods: Our mouse model was generated using floxed exon 8 BMAL1 mice crossed with kidney-specific cadherin Cre+ mice to generate KS-BMAL1 KO. Floxed Cre- littermates were used as CNTL. Male mice were implanted with telemeter devices for 24-hour BP monitoring before and during administration of a low potassium diet over 7 days (0% K, 0.2% Na) and followed by a low potassium, high salt diet for 10 days (0% K, 2% Na, N=7-8). Two-way ANOVA was used to compare diet and genotype effects. Results: Following potassium depletion alone, systolic BP significantly decreased in both genotypes (P<0.05). Compared to baseline, KS-BMAL KO did not exhibit the increase in BP as seen in CNT on the potassium deficient, high salt diet (CNTL: 125±2 to 132±1; KO: 123±2 to 122±2 mmHg). Neither diet nor genotype altered circadian rhythms in BP. Conclusions: BMAL1 in renal distal segments contributes to BP regulation. KS-BMAL1 KO appear to be protected from the substantial increase in BP that occurred in CNTL in response to a low potassium/high salt diet. These data suggest that BMAL1 contributes to the protection from salt-sensitive hypertension in the setting of a low potassium diet.

Adrenal adaptation in potassium-depleted men: role of progesterone?

BackgroundIn rodents, the stimulation of adrenal progesterone is necessary for renal adaptation under potassium depletion. Here, we sought to determine the role of progesterone in adrenal adaptation in potassium-depleted healthy human volunteers and compared our findings with data collected in patients with Gitelman syndrome (GS), a salt-losing tubulopathy.MethodsTwelve healthy young men were given a potassium-depleted diet for 7 days at a tertiary referral medical centre (NCT02297048). We measured by liquid chromatography coupled to tandem mass spectroscopy plasma steroid concentrations at Days 0 and 7 before and 30 min after treatment with tetracosactide. We compared these data with data collected in 10 GS patients submitted to tetracosactide test.ResultsThe potassium-depleted diet decreased plasma potassium in healthy subjects by 0.3 ± 0.1 mmol/L, decreased plasma aldosterone concentration by 50% (P = 0.0332) and increased plasma 17-hydroxypregnenolone concentration by 45% (P = 0.0232) without affecting other steroids. CYP17 activity, as assessed by 17-hydroxypregnenolone/pregnenolone ratio, increased by 60% (P = 0.0389). As compared with healthy subjects, GS patients had 3-fold higher plasma concentrations of aldosterone, 11-deoxycortisol (+30%) and delta 4-androstenedione (+14%). Their post-tetracosactide progesterone concentration was 2-fold higher than that of healthy subjects and better correlated to plasma potassium than to plasma renin.ConclusionThe increase in 17-hydroxypregnenolone concentration after mild potassium depletion in otherwise healthy human subjects suggests that 17 hydroxylation of pregnenolone prevents the increase in progesterone observed in potassium-depleted mice. The unexpected over-response of non-mineralocorticoid steroids to tetracosactide in GS subjects suggests that the adrenal system not only adapts to sodium depletion but may also respond to hypokalaemia.