Expanding the spectrum of genetic mutations in antenatal Bartter syndrome type II

Bartter syndrome (BS) is a group of genetic disorders characterized by hypokalemic metabolic alkalosis, hyponatremia and elevated renin and aldosterone plasma concentrations. BS type II is caused by mutations in the KCNJ1 gene and usually presents with transient hyperkalemia. We report here a novel KCNJ1 mutation in a male neonate, prematurely born after a pregnancy complicated by polyhydramnios. The infant presented with typical clinical and laboratory findings of BS type II, such as hyponatremia, hypochloremic metabolic alkalosis, severe weight loss, elevated renin and aldosterone levels and transient hyperkalemia in the early postnatal period, which were later normalized. Molecular analysis revealed a compound heterozygous mutation in the KCNJ1 gene, consisting of a novel K76E and an already described V315G mutation, both affecting functional domains of the channel protein. Typical manifestations of antenatal BS in combination with hyperkalemia should prompt the clinician to search for mutations in the KCNJ1 gene first.     

Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD

Background and objectives

Hyperkalemia affects up to 10% of patients with CKD. Sodium polystyrene sulfonate has long been prescribed for this condition, although evidence is lacking on its efficacy for the treatment of mild hyperkalemia over several days. This study aimed to evaluate the efficacy of sodium polystyrene sulfonate in the treatment of mild hyperkalemia.

Design, setting, participants, & measurements

In total, 33 outpatients with CKD and mild hyperkalemia (5.0–5.9 mEq/L) in a single teaching hospital were included in this double–blind randomized clinical trial. We randomly assigned these patients to receive either placebo or sodium polystyrene sulfonate of 30 g orally one time per day for 7 days. The primary outcome was the comparison between study groups of the mean difference of serum potassium levels between the day after the last dose of treatment and baseline.

Results

The mean duration of treatment was 6.9 days. Sodium polystyrene sulfonate was superior to placebo in the reduction of serum potassium levels (mean difference between groups, −1.04 mEq/L; 95% confidence interval, −1.37 to −0.71). A higher proportion of patients in the sodium polystyrene sulfonate group attained normokalemia at the end of their treatment compared with those in the placebo group, but the difference did not reach statistical significance (73% versus 38%; P=0.07). There was a trend toward higher rates of electrolytic disturbances and an increase in gastrointestinal side effects in the group receiving sodium polystyrene sulfonate.

Conclusions

Sodium polystyrene sulfonate was superior to placebo in reducing serum potassium over 7 days in patients with mild hyperkalemia and CKD.     

Patiromer for the treatment of hyperkalemia

ABSTRACT

Introduction

Hyperkalemia is a chronic and life-threatening electrolyte disorder that affects millions of patients around the world with decreased kidney function, hypertension, and heart failure. Recently newer oral potassium-binding agents have been approved for clinical use, as an alternative to the decades long use of sodium polystyrene sulfonate. This review will focus on the patiromer and its use in reducing hyperkalemia.     

非静脉转流原位肝移植再灌注期高血钾致心跳骤停的救治:附3例报告

分析3例非静脉转流下原位肝移植术下腔静脉、门静脉开放时发生高钾血症致心跳骤停的原因,探讨防治措施。     

低氧和复氧致心肌电生理的改变及高钾液的影响

分别用细胞内微电极和Ｌａｎｇｅｎｄｏｒｆｆ心脏灌流技术在低氧复氧豚鼠心肌条和离体大鼠心脏上观察到：缺血多由折返机制产生以室性早搏（发生率为５／８）为主的心率失常；再灌注心律失常有触发机制参与，主要形成室颤（发生率为７／８）。高钾（１３ｍＭ／Ｌ）有类似低氧条件所致的电生理改变，且通过减少复氧早期钙离子内流而抑制后除极所致触发活动，并可阻断低氧心肌的折返通路而抑制再灌注心律失常。     

Advances in treatment of hyperkalemia in chronic kidney disease

Introduction: Hyperkalemia is a frequent electrolyte disorder associated with life-threatening cardiac arrhythmias and sudden death. Patients prone to hyperkalemia have chronic kidney disease (CKD) either alone or in conjunction with diabetes or heart failure (HF). Although agents inhibiting the renin–angiotensin–aldosterone–system (RAAS) are currently the first-line treatments toward cardio- and nephroprotection, their administration often leads to potassium elevation in such patients and results in high rates of treatment discontinuation.

Areas covered: This article provides an overview of factors interfering with potassium homeostasis and discusses emerging potassium-lowering therapies for long-term management of hyperkalemia.

Expert opinion: In recent randomized clinical studies, two new oral potassium-exchanging compounds, patiromer and sodium zirconium cyclosilicate, were shown to effectively normalize elevated serum potassium and chronically maintain potassium homeostasis in hyperkalemic patients treated with RAAS blockers. Both agents exhibit good tolerability and were not associated with serious adverse effects. Although additional research is required, these drugs are promising for lowering the risk of incident hyperkalemia associated with RAAS blockade use in people with diabetes or HF who have CKD. They also provide the opportunity to test whether patients who could not previously receive RAAS blockade may benefit from their cardio- and renoprotective effects.     

Hyperkalemia‐Induced Brugada Pattern with Electrical Alternans

The Brugada syndrome is a genetic disease (mutation of the SCN5A gene) that predisposes to syncope and life‐threatening sudden cardiac death. The case highlights the importance of recognizing hyperkalemia, as potential triggers of the acquired Brugada sign with electrical alternans.     

Dysmorphic neuromuscular junctions associated with motor ability in cerebral palsy

Cerebral palsy (CP) is the most prevalent neurologic disease in children and a leading cause of severe physical disability. Research and clinical experience indicate that children with CP have abnormal neuromuscular junctions (NMJs), and we present evidence that nonapposition of neuromuscular junction components is associated with the severity of motor system deficit in CP. Leg muscle biopsies collected from ambulatory (n = 21) or nonambulatory (n = 38) CP patients were stained in order to detect acetylcholine receptor (AChR) and acetylcholine esterase (AChE). Image analysis was used to calculate the extra-AChE spread (EAS) of AChR staining to estimate the amount of AChR occurring outside the functional, AChE-delimited NMJ. Nonambulatory children exhibited higher average EAS (P = 0.025) and had a greater proportion of their NMJs with significantly elevated EAS (P = 0.023) than ambulatory children. These results indicate that physical disability in children with CP is associated with structurally dysmorphic NMJs, which has important implications for the management of CP patients, especially during surgery and anesthesia.     

Treatment of hyperkalemia in children with intravenous salbutamol

The aim of this study is to investigate the efficacy and safety of intravenous salbutamol in hyperkalemia. Fourteen children with chronic renal failure, three with acute renal failure and hyperkalemia were treated by intravenous infusions of 4μg/kg salbutamol. Reductions in the mean plasma potassium (K⁺) concentrations obtained at 40 and 120 min after therapy were statistically significant when compared with the mean plasma K⁺ concentration at the beginning of therapy (P < 0.01).     

Clinical Management in Systemic Type Pseudohypoaldosteronism Due to SCNN1B Variant and Literature Review

Systemic pseudohypoaldosteronism (PHA) is a rare, salt-wasting syndrome that is caused by inactivating variants in genes encoding epithelial sodium channel subunits. Hyponatremia, hyperkalemia, metabolic acidosis, increased aldosterone and renin levels are expected findings in PHA. Clinical management is challenging due to high dose oral replacement therapy. Furthermore, patients with systemic PHA require life-long therapy. Here we report a patient with systemic PHA due to SCNN1B variant whose hyponatremia and hyperkalemia was detected at the 24^th hour of life. Hyperkalemia did not improve with conventional treatments and dialysis was required. He also developed myocarditis and hypertension in follow-up. Challenges for diagnosis and treatment in this patient are discussed herein. In addition, published evidence concerning common features of patients with SCNN1B variant are reviewed.