Correcting Serum Potassium in Hypokalemia to Improve Outcomes

Chronic kidney disease (CKD) is a public health concern worldwide. The prevalence of kidney failure requiring renal replacement therapy (RRT) is increasing, with an expectation of doubling of the numbers in this decade.

The numbers are expected to increase substantially in Asia. In 2016, the estimated number of patients receiving RRT in Thailand was 346 per million, representing a tripling from the previous decade. The modality of choice for RRT in Thailand is peritoneal dialysis, and the number of patients receiving peritoneal dialysis has increased 10-fold over the past 10 years.

Hypokalemia, serum potassium level below 3.5 mEq/L, is a frequent complication of peritoneal dialysis. In results of PDOPPS (Peritoneal Dialysis Outcomes and Practice Patterns Study), there is wide variation in the prevalence of hypokalemia in patients receiving peritoneal dialysis among participating countries (from 3% to 47%).

Hypokalemia is a common electrolyte abnormality in that patient population and had been associated with increased risks of peritonitis and death. It is unknown whether correction of hypokalemia improves those outcomes. Previous studies have suggested that low dietary potassium, as opposed to increased potassium excretion, is the primary contributing factor to hypokalemia in maintenance peritoneal dialysis.

There are no data evaluating whether correction of hypokalemia through potassium supplementation would mitigate the risk of peritonitis. Watthikorn Pichitporn, MD, and colleagues conducted a multicenter, open-label, prospective, randomized controlled trial to examine the efficacy and safety of protocol-based potassium treatment over 12 months for reducing peritonitis in peritoneal dialysis patients with hypokalemia. Results were reported in the American Journal of Kidney Diseases [2022;80(5):580-588].

The study cohort included adults ≥18 years of age receiving peritoneal dialysis with hypokalemia, defined as one of two of these criteria in the previous 6 months: (1) spot serum potassium values below 3.5 mEq/L on at least three measurements or (2) an average serum potassium value below 3.5 mEq/L. Exclusion criteria were peritonitis within 3 months, receiving hybrid RRT, Child class C liver cirrhosis, chronic infection, cancer, or gastrointestinal disease. Randomization was stratified according to center and residual urine output (≤100 or >100 ml/day).

The study interventions were random assignment to either protocol-based potassium supplementation (titratable dose of oral potassium chloride to maintain serum potassium of 4-5 mEq/L) or conventional potassium supplementation (reactive supplementation when serum potassium is <3.5 mEq/L) over 52 week. Intention-to-treat analyses using Cox proportional hazards regression were used to compare treatment groups.

The primary outcome of interest was the time from randomization to the first episode of peritonitis (any organism). Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and conversion to hemodialysis.

Screening occurred between January 2020 and May 2021. A total of 809 patients were screened; of those, 208 were eligible and 167 underwent 1:1 randomization. Following randomization, seven participants in the intervention group did not complete the study. Median study follow-up was 401 days. The two groups were similar in follow-up time.

The two groups were balanced in baseline characteristics. The mean time-averaged serum potassium concentrations at baseline were similar in the intervention and control groups (3.32 and 3.35 mEq/L, respectively). During the study period, the average serum potassium level in the intervention group increased to 4.04 mEq/L at the first 4 weeks and remained at levels ranging from 4.23 to 4.45 mEq/L. In the control group, the average serum potassium level ranged from 3.47 to 3.74 mEq/L.

Further, in the protocol-based treatment group, serum potassium was achieved at target ranges and was significantly higher than with conventional treatment  throughout the study period. Time-averaged serum potassium level in the intervention group was 3.97 mEq/L throughout the study period, compared with 3.47 mEq/L in the control group (P<.001).

Thirteen participants in the intervention group experienced peritonitis (13 episodes) compared with 24 participants in the control group (25 episodes) in the follow-up period. Median time to the first episode of peritonitis was significantly longer in the intervention group than in the control group (233 days vs 133 days, respectively; P=.03). The proportion of participants without peritonitis was significantly greater in the intervention group than in the control group (29% vs 15%, respectively; P=.03). There was no statistically significant difference between the two groups in the overall rate of peritonitis.

The intervention group had a significantly lower hazard of peritonitis (hazard ratio, 0.47; 95% CI, 0.24-0.93) compared with the control group. There were no significant differences in hazards between the two groups for any of the secondary outcomes.

Mean prescribed potassium supplement dosages were 25 mEq/d in the intervention group and 12 mEq/d in the control group. A total of 69 participants in the intervention group (81%) received potassium supplementation throughout the entire study period; the remainder had potassium temporarily withheld due to hyperkalemia.

Oral potassium supplements were generally well tolerated in both groups. Three participants in the intervention group were withdrawn from the study due to diarrhea. Hyperkalemia (defined as serum potassium level >6 mEq/L) occurred in participants in the intervention group only, with an incidence of 4% (3/85, one episode per participant). All episodes of hyperkalemia were asymptomatic and had no associated characteristic electrocardiogram changes.

Limitations to the study findings cited by the authors included calculating the sample size assuming no competing event; the open-label design that may have introduced observer and performance biases; not measuring potassium in urine, peritoneal dialysis effluent, and diet; and difficulty in follow-up with some participants due to the study being conducted during the COVID-19 pandemic.

In conclusion, the researchers said, “Protocol-based oral potassium supplementation to maintain serum potassium concentration in the range of 4-5 mEq/L appears to be safe and may reduce the risk of peritonitis in hypokalemic peritoneal dialysis patients compared with reactive potassium supplementation when serum potassium falls below 3.5 mEq/L.”

Takeaway Points

  1. Patients on peritoneal dialysis may experience hypokalemia, an electrolyte abnormality that is associated with increased risk of peritonitis and death.
  2. Researchers conducted a study to examine whether correction of hypokalemia via protocol-based potassium supplementation or conventional potassium supplementation would improve those outcomes.
  3. During the mean study follow-up period, serum potassium levels in the protocol-treated group increased to 4.86 mEq/L compared with 3.57 mEq/L in the group treated conventionally.