Correction of Hypokalemia in Peritoneal Dialysis Patients May Decrease Peritonitis Risk

Abstract

Related Article, p. 580 While interest in peritoneal dialysis (PD) is growing in many parts of the world given its patient-centric approach and favorable cost profile, peritonitis remains a major problem. Some risk factors have been identified, but many of these are not modifiable. One that deserves closer scrutiny is hypokalemia, which has been associated with an increased risk for peritonitis.1Chuang Y.W. Shu K.H. Yu T.M. Cheng C.H. Chen C.H. Hypokalaemia: an independent risk factor of Enterobacteriaceae peritonitis in CPAD patients.Nephrol Dial Transpl. 2009; 2416031608https://doi.org/10.1093/ndt/gfn709Crossref Scopus (69) Google Scholar, 2Liu D. Lin Y. Gong N. et al.Degree and duration of hypokalemia associated with peritonitis in patients undergoing peritoneal dialysis.Int J Clinic Pract. 2021; 75e14188https://doi.org/10.1111/ijcp.14188Crossref Scopus (6) Google Scholar, 3Davies S.J. Zhao J. Morgenstern H. et al.Low serum potassium levels and clnical outcomes in peritoneal dialysis- international results from PDOPPS.Kidney Int Rep. 2020; 6: 313-345https://doi.org/10.1016/j.ekir.2020.11.021Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar The impact of treatment of hypokalemia on peritonitis risk has not been previously closely examined. In the article by Pichitporn et al4Pichitporn W. Kanjanabuch T. Phannajit J. et al.Efficacy of potassium supplementation in hypokalemic patients receiving peritoneal dialysis: a randomized controlled trial.Am J Kidney Dis. 2022; 80: 580-588https://doi.org/10.1053/j.ajkd.2022.03.013Abstract Full Text Full Text PDF Scopus (1) Google Scholar appearing in this issue of AJKD, 167 PD patients with hypokalemia (defined as either 3 measurements of serum potassium of <3.5 mEq/L or an average serum potassium level <3.5 mEq/L) were randomly assigned to receive potassium supplements in a protocolized approach to maintain the serum potassium between 4 and 5 mEq/L (4.36 mEq/L achieved) versus a more conventional and ad hoc approach managed by the treating nephrologist (3.57 mEq/L achieved). The primary outcome was time to first peritonitis after entry into the study, and the median follow-up was 401 days. The study was conducted at 6 PD centers in Thailand. Virtually all the patients were on continuous ambulatory PD. The outcomes demonstrated in the study are shown in Table 1. Median time to first peritonitis was 223 days in the protocol-treated group (who maintained a potassium level above 4 mEq/L throughout the study follow-up), versus 133 days in the conventional group, whose potassium levels remained below 4 mEq/L (P = 0.03). Furthermore, fewer patients developed peritonitis with the standardized potassium supplementation intervention versus those treated by their nephrologists in an ad hoc manner (15% [13/85] vs 29% [24/82], respectively, P = 0.03). In a finding that was statistically significant and clinically important, the protocol-based patients had a lower hazard ratio of peritonitis (hazard ratio, 0.47 [95% CI, 0.24-0.93]).Table 1Comparison of the Protocolized Potassium Replacement Group to the Physician-Driven Replacement ApproachIntervention Group (K Maintained ≥4 mEq/L)Control Group (K Maintained 3.5 mEq/L)No. of patients8582Follow-up time, d378407PD time at risk during the study, y54.059.5Mean K dose, mEq/d25±1312±17Time-averaged K level, mEq/L3.973.47Time to peritonitis, d223133Proportion of patients peritonitis-free85%71%HR for peritonitis0.47 (0.24-0.93)1.00 (reference)HR for peritonitis, controlled for age, DM0.52 (0.25-1.03)1.00 (reference)Peritonitis episodes per year at risk0.240.42 Due to contaminationaPotential cause of peritonitis based on organism, with contamination as the cause ascribed to S. aureus, Coagulase-negative Staphylococcus, or no growth, and an enteric cause inferred from Enterobacteriaceae or Acinetobacter.0.040.15 Enteric causeaPotential cause of peritonitis based on organism, with contamination as the cause ascribed to S. aureus, Coagulase-negative Staphylococcus, or no growth, and an enteric cause inferred from Enterobacteriaceae or Acinetobacter.0.060.14 Other causeaPotential cause of peritonitis based on organism, with contamination as the cause ascribed to S. aureus, Coagulase-negative Staphylococcus, or no growth, and an enteric cause inferred from Enterobacteriaceae or Acinetobacter.0.150.12Based on data in Pichitporn.4Pichitporn W. Kanjanabuch T. Phannajit J. et al.Efficacy of potassium supplementation in hypokalemic patients receiving peritoneal dialysis: a randomized controlled trial.Am J Kidney Dis. 2022; 80: 580-588https://doi.org/10.1053/j.ajkd.2022.03.013Abstract Full Text Full Text PDF Scopus (1) Google Scholar Abbreviations: DM, diabetes mellitus; HR, hazard ratio; K, potassium.a Potential cause of peritonitis based on organism, with contamination as the cause ascribed to S. aureus, Coagulase-negative Staphylococcus, or no growth, and an enteric cause inferred from Enterobacteriaceae or Acinetobacter. Open table in a new tab Based on data in Pichitporn.4Pichitporn W. Kanjanabuch T. Phannajit J. et al.Efficacy of potassium supplementation in hypokalemic patients receiving peritoneal dialysis: a randomized controlled trial.Am J Kidney Dis. 2022; 80: 580-588https://doi.org/10.1053/j.ajkd.2022.03.013Abstract Full Text Full Text PDF Scopus (1) Google Scholar Abbreviations: DM, diabetes mellitus; HR, hazard ratio; K, potassium. This study demonstrates that correction of hypokalemia in a systematic manner that normalizes potassium levels can lead to a lesser risk of peritonitis.4Pichitporn W. Kanjanabuch T. Phannajit J. et al.Efficacy of potassium supplementation in hypokalemic patients receiving peritoneal dialysis: a randomized controlled trial.Am J Kidney Dis. 2022; 80: 580-588https://doi.org/10.1053/j.ajkd.2022.03.013Abstract Full Text Full Text PDF Scopus (1) Google Scholar The mean dose of potassium supplement was 25 mEq/d in the intervention group, which kept the potassium level above 4 mEq/L throughout the study. In contrast, the group managed with ad hoc supplementation by their nephrologists had potassium levels hovering around 3.5 mEq/L and were consistently below 4 mEq/L, with a mean supplemental dose of 12 mEq/d. This is an important outcome, especially since the outlined approach of standardized potassium supplementation could be easily implemented by any PD program. In contrast to what happens in the setting of hemodialysis, a substantial proportion of PD patients are hypokalemic.4Pichitporn W. Kanjanabuch T. Phannajit J. et al.Efficacy of potassium supplementation in hypokalemic patients receiving peritoneal dialysis: a randomized controlled trial.Am J Kidney Dis. 2022; 80: 580-588https://doi.org/10.1053/j.ajkd.2022.03.013Abstract Full Text Full Text PDF Scopus (1) Google Scholar In 1 single-center study,5Khan A.N. Bernardini J. Johnston J.R. Piraino B. Hypokalemia in peritoneal dialysis patients.Perit Dial Intern. 1996; 16 (652-652)Google Scholar 29% of the PD patients required potassium supplementation, with a mean dose of 22 mEq/d (similar to the dose prescribed in the current study in the protocol arm). With supplementation the mean initial potassium level of 3.4 mEq/L increased to 3.9 mEq/L. Of note, the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) demonstrated that a much higher proportion of patients in Thailand had potassium levels less than 4.0 mEq/L (76% of PD patients) compared to the other countries studied (which ranged between 24% and 39% among Australia/New Zealand, Canada, Japan, United Kingdom, and United States).3Davies S.J. Zhao J. Morgenstern H. et al.Low serum potassium levels and clnical outcomes in peritoneal dialysis- international results from PDOPPS.Kidney Int Rep. 2020; 6: 313-345https://doi.org/10.1016/j.ekir.2020.11.021Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar This is important to note, as the current study was conducted in Thailand. In PDOPPS, examining 7,596 patients across 216 facilities, patients with lower potassium level tended to have worse nutritional indicators, including lower body mass index, lower serum albumin concentrations, and higher levels of inflammatory markers.3Davies S.J. Zhao J. Morgenstern H. et al.Low serum potassium levels and clnical outcomes in peritoneal dialysis- international results from PDOPPS.Kidney Int Rep. 2020; 6: 313-345https://doi.org/10.1016/j.ekir.2020.11.021Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar) Do we know the mechanism for the reduction of peritonitis risk after optimal correction of hypokalemia? This is not entirely clear. The authors hypothesize that the better results in the intervention group may be due to better muscle strength resulting in improved performance of PD, better cellular function including immune defense, and improved gut motility. Perhaps there are some hints to be obtained by analyzing the organism-specific rates (Table 1) in the 2 groups. Contamination during a PD exchange often leads to peritonitis owing to Staphylococcus; however, culture-negative peritonitis is generally considered to be due to contamination as well. The study by Pichitporn et al was not powered to examine the question of organism-specific peritonitis. However, although not a statistically significant difference, peritonitis owing to possible contamination (including S. aureus, coagulase-negative Staphylococcus, and no growth) was almost 4 times higher in the ad hoc supplementation group than the group whose potassium levels were increased to 4 mEq/L or higher through standardized supplementation. Why could patients with hypokalemia be at higher risk of peritonitis owing to contamination? If patients with hypokalemia have poorer nutritional status, higher levels of inflammatory markers, and lower albumin concentrations, this might put them at increased risk.3Davies S.J. Zhao J. Morgenstern H. et al.Low serum potassium levels and clnical outcomes in peritoneal dialysis- international results from PDOPPS.Kidney Int Rep. 2020; 6: 313-345https://doi.org/10.1016/j.ekir.2020.11.021Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Poor nutritional status, and particularly low serum albumin concentration, is a risk factors for peritonitis.6Wang I. Bernardini J. Piraino B. Fried L. Albumin at the start of peritoneal dialysis predicts the development of peritonitis.Am J Kidney Dis. 2003; 41: 664-669https://doi.org/10.1053/ajkd.2003.50128Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar Indeed, in a study by Wang et al,6Wang I. Bernardini J. Piraino B. Fried L. Albumin at the start of peritoneal dialysis predicts the development of peritonitis.Am J Kidney Dis. 2003; 41: 664-669https://doi.org/10.1053/ajkd.2003.50128Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar coagulase-negative Staphylococcus, S. aureus, and non-Pseudomonas Gram-negative peritonitis rates were strikingly higher in those with an initial serum albumin concentration of less than 2.9 mg/dL. Correcting hypokalemia may well improve the immune function of the peritoneal space. More study is needed. Some studies have shown that hypokalemia is associated with an increased risk of Enterobacteriaceae peritonitis.1Chuang Y.W. Shu K.H. Yu T.M. Cheng C.H. Chen C.H. Hypokalaemia: an independent risk factor of Enterobacteriaceae peritonitis in CPAD patients.Nephrol Dial Transpl. 2009; 2416031608https://doi.org/10.1093/ndt/gfn709Crossref Scopus (69) Google Scholar The theory is that hypokalemia slows gut motility and this may lead to an increased risk of translocation of such bacteria across the bowel wall, leading to peritonitis. In the current study, the rate of peritonitis with Enterobacter and Acinetobacter (both found in the gut) was more than double in the control group versus those whose potassium level was maintained above 4 mEq/L during the study. This again raises the debatable question as to whether hypokalemia can influence peritonitis rates owing to enteric organisms, possibly through an effect on gut motility. Pseudomonas-related peritonitis is often due to catheter-related infections, and one would not expect this to be impacted by the potassium level. The etiology of streptococcal infection, while not well studied, might be from transient bacteremia due to poor dental hygiene, again, not likely to be impacted by potassium levels. Further studies examining the impact of correction of hypokalemia on organism-specific peritonitis are warranted. Clinicians caring for PD patients need to pay close attention to this carefully designed multicenter randomized controlled trial examining the effect that normalizing the serum potassium levels has on delaying the presentation of peritonitis compared to conventionally treated hypokalemic patients. Such treatment is easily accomplished. We should maintain our PD patients’ potassium level at 4 mEq/L or above. This approach is safe given that only 3 patients (4%) of the protocol-treated patients had hyperkalemia, which was asymptomatic and easily reversed.4Pichitporn W. Kanjanabuch T. Phannajit J. et al.Efficacy of potassium supplementation in hypokalemic patients receiving peritoneal dialysis: a randomized controlled trial.Am J Kidney Dis. 2022; 80: 580-588https://doi.org/10.1053/j.ajkd.2022.03.013Abstract Full Text Full Text PDF Scopus (1) Google Scholar Larger trials are needed to examine the impact of correction of hypokalemia on prevention of organism-specific peritonitis. This may provide better insight into the mechanism of the increased peritonitis risk with hypokalemia. None. The author declares that she has no relevant financial interests. Dr Piraino is a member of PDOPPS, on the medical advisory board of the National Kidney Foundation of the Alleghenies, and on the editorial boards of the Journal of the American Society of Nephrology, the Clinical Journal of the American Society of Nephrology, and Peritoneal Dialysis International. Received April 26, 2022, in response to an invitation from the journal. Direct editorial input from an Associate Editor and a Deputy Editor. Accepted in revised form June 8, 2022. Efficacy of Potassium Supplementation in Hypokalemic Patients Receiving Peritoneal Dialysis: A Randomized Controlled TrialAmerican Journal of Kidney DiseasesVol. 80Issue 5PreviewHypokalemia is a common electrolyte abnormality in patients on peritoneal dialysis (PD) and has been associated with increased risks of peritonitis and death. Whether correction of hypokalemia improves these outcomes is unknown. Full-Text PDF