title: Urinary potassium excretion, renal ammoniagenesis, and risk of graft failure and mortality in renal transplant recipients.
abstract: Renal transplant recipients (RTRs) have commonly been urged to limit their potassium intake during renal insufficiency and may adhere to this principle after transplantation. Importantly, in experimental animal models, low dietary potassium intake induces kidney injury through stimulation of ammoniagenesis. In humans, low potassium intake is an established risk factor for high blood pressure.
  
  
  
  We hypothesized that low 24-h urinary potassium excretion [UKV; urinary potassium concentration × volume], the gold standard for assessment of dietary potassium intake, represents a risk factor for graft failure and mortality in RTRs. In secondary analyses, we aimed to investigate whether these associations could be explained by ammoniagenesis, plasma potassium, or blood pressure.
  
  
  
  In a prospective cohort of 705 RTRs, we assessed dietary potassium intake by a single 24-h UKV and food-frequency questionnaires. Cox regression analyses were used to investigate prospective associations with outcome.
  
  
  
  We included 705 stable RTRs (mean ± SD age: 53 ± 13 y; 57% men) at 5.4 y (IQR: 1.9-12.0 y) after transplantation and 253 kidney donors. Mean ± SD UKV was 73 ± 24 mmol/24 h in RTRs compared with 85 ± 25 mmol/24 h in kidney donors. During follow-up for 3.1 y (IQR: 2.7-3.9 y), 45 RTRs developed graft failure and 83 died. RTRs in the lowest sex-specific tertile of UKV (women, <55 mmol/24 h; men, <65 mmol/24 h) had an increased risk of graft failure (HR: 3.70; 95% CI: 1.64, 8.34) and risk of mortality (HR; 2.66; 95% CI: 1.53, 4.61), independent of potential confounders. In causal path analyses, 24-h urinary ammonia excretion, plasma potassium, and blood pressure did not affect these associations.
  
  
  
  Our results indicate that low UKV is associated with a higher risk of graft failure and mortality in RTRs. Specific attention for adequate potassium intake after transplantation seems warranted. This trial was registered at clinicaltrials.gov as NCT02811835.
authors.affiliation: Departments of Nephrology and m.f.eisenga@umcg.nl.
authors.forename: Michele F
authors.identifier: 0000-0002-2484-6233
authors.initials: MF
authors.lastname: Eisenga
authors.affiliation: Departments of Nephrology and.
authors.forename: Lyanne M
authors.initials: LM
authors.lastname: Kieneker
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, Netherlands and.
authors.forename: Sabita S
authors.initials: SS
authors.lastname: Soedamah-Muthu
authors.affiliation: Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; and.
authors.forename: Else
authors.initials: E
authors.lastname: van den Berg
authors.affiliation: Departments of Nephrology and.
authors.forename: Petronella E
authors.initials: PE
authors.lastname: Deetman
authors.affiliation: Departments of Nephrology and.
authors.forename: Gerjan J
authors.initials: GJ
authors.lastname: Navis
authors.affiliation: Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; and.
authors.forename: Reinold Ob
authors.initials: RO
authors.lastname: Gans
authors.affiliation: Departments of Nephrology and.
authors.forename: Carlo Ajm
authors.initials: CA
authors.lastname: Gaillard
authors.affiliation: Departments of Nephrology and.|Top Institute Food and Nutrition, Wageningen, Netherlands.
authors.forename: Stephan Jl
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Departments of Nephrology and.
authors.forename: Michel M
authors.initials: MM
authors.lastname: Joosten
mesh_terms: D000328:Adult; D000368:Aged; D000641:Ammonia / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000401:mortality*; D006085:Graft Survival; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000209:etiology; D007668:Kidney; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D017419:Potassium, Dietary / Q000008:administration & dosage / Q000009:adverse effects / Q000652:urine*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D017419:Potassium, Dietary; D000641:Ammonia
keywords: ammoniagenesis; dietary potassium intake; graft failure; kidney transplantation; mortality; urinary potassium excretion