Hypokalemia, its contributing factors and renal outcomes in patients with chronic kidney disease

PLoS One. 2013 Jul 2;8(7):e67140. doi: 10.1371/journal.pone.0067140. Print 2013.


Background: In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated.

Design participants & measurements: 2500 participants with CKD stage 1-4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used.

Results: The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m(2). Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03-3.22) in sK <3.5mEq/L and 1.67 (95% CI,1.19-2.35) in sK = 3.5-4 mEq/L, respectively, compared with sK = 4.5-5 mEq/L. Hyperkalemia defined as sK >5 mEq/L conferred 1.6-fold (95% CI,1.09-2.34) increased risk of ESRD compared with sK = 4.5-5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range.

Conclusion: In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.

MeSH terms

  • Aged
  • C-Reactive Protein / metabolism
  • Diuretics / therapeutic use
  • Female
  • Glomerular Filtration Rate
  • Hemoglobins / metabolism
  • Humans
  • Hypokalemia / complications*
  • Hypokalemia / drug therapy
  • Hypokalemia / metabolism
  • Hypokalemia / pathology
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / pathology
  • Severity of Illness Index
  • Treatment Outcome


  • Diuretics
  • Hemoglobins
  • C-Reactive Protein

Grant support

The authors have no support or funding to report.