title: Renal Insufficiency in Concert with Renin-angiotensin-aldosterone Inhibition Is a Major Risk Factor for Hyperkalemia Associated with Low-dose Trimethoprim-sulfamethoxazole in Adults.
abstract: OBJECTIVE
  Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) is commonly used to prevent pneumocystis pneumonia in daily practice. Previous reports have shown a relationship between high- or standard-dose of TMP-SMX and hyperkalemia, however it remains unclear whether this is true for low-dose TMP-SMX. In this study we sought to determine the risk factors for hyperkalemia associated with low-dose TMP-SMX.
  
  
  METHODS
  In this retrospective cohort study, 186 consecutive adult patients who received TMP-SMX as prophylaxis for pneumocystis pneumonia from January 2014 to January 2015 were evaluated. Data on the patients' age, gender, baseline estimated glomerular filtration rate (eGFR), baseline serum potassium, maximum serum potassium, duration reaching the maximal serum potassium level, dosage, and concomitant use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), β-blockers, non-steroidal anti-inflammatory drugs and potassium-sparing diuretics were retrospectively collected. Hyperkalemia was defined as a serum potassium level ≥5 mEq/L. Univariate and multivariate analyses were performed.
  
  
  RESULTS
  The median age of the patients was 66 years and 51.1% were men. Hyperkalemia associated with low-dose TMP-SMX was observed in 32 patients (17.2%). The median duration to reach the maximal serum potassium level was 12 days. The multivariate logistic regression analysis identified renal insufficiency to be a major risk factor for hyperkalemia associated with low-dose TMP-SMX (eGFR <60 mL/min/1.73 m(2), adjusted OR 4.62). Moreover, in the subpopulation of patients with renal insufficiency, ACEi/ARB use was considered to be a major risk factor for hyperkalemia (adjusted OR 3.96).
  
  
  CONCLUSIONS
  Renal insufficiency in concert with ACEi/ARB use is a major risk factor for hyperkalemia induced by low-dose TMP-SMX.
authors.affiliation: Division of Rheumatology, Matsuyama Red Cross Hospital, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Higashioka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Niiro
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kensuke
authors.initials: K
authors.lastname: Oryoji
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kamada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mizuki
authors.forename: Eisuke
authors.initials: E
authors.lastname: Yokota
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000188:drug therapy*; D051437:Renal Insufficiency / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination