title: Lithium-induced nephropathy: Rate of progression and prognostic factors.
abstract: BACKGROUND
  Long-term lithium administration in humans may lead to chronic tubulointerstitial nephritis, which develops very slowly. Its progression to end-stage renal disease (ESRD) has been rarely reported. The aim of this study is to document the rate of progression of lithium-induced nephropathy and its prognostic factors, and to provide an estimation of the percentage of lithium-induced ESRD in France.
  
  
  METHODS
  Two groups have been studied: 54 patients with lithium-induced renal failure, nine of whom underwent renal biopsy; and 20 patients who were referred for systematic renal biopsy, 14 of whom were subsequently followed up. In addition, a survey of lithium-induced ESRD was conducted in French dialysis centers.
  
  
  RESULTS
  The mean annual loss of creatinine clearance in patients with lithium-induced nephropathy was 2.29 mL/min. Among 74 patients, 12 reached ESRD at a mean age of 65 years. Creatinine clearance at referral and at last follow-up was inversely related to the duration of lithium therapy in both univariate and multivariate analyses adjusting for age, gender, hypertension, and proteinuria. The degree of interstitial fibrosis on renal biopsy was also related to the lithium duration and cumulative dose. It was predictive of the final creatinine clearance. About 35% of the patients tested had moderate hypercalcemia, due to hyperparathyroidism. The prevalence of lithium-related ESRD in France was estimated as two per 1000 dialysis patients. The average latency between onset of lithium therapy and ESRD was 20 years.
  
  
  CONCLUSIONS
  Lithium-induced chronic renal disease is slowly progressive. Its rate of progression is related to the duration of lithium administration. Lithium-related ESRD represents 0.22% of all causes of ESRD in France. Regular monitoring of estimated creatinine clearance is mandatory in long-term lithium-treated patients.
authors.affiliation: AP-HP, Hôpital Necker, Service de Néphrologie et Université Paris V, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Presne
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Noël
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Stengel
authors.forename: Christian
authors.initials: C
authors.lastname: Even
authors.forename: Henri
authors.initials: H
authors.lastname: Kreis
authors.forename: Françoise
authors.initials: F
authors.lastname: Mignon
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grünfeld
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects*; D001706:Biopsy; D001714:Bipolar Disorder / Q000188:drug therapy*; D002118:Calcium / Q000097:blood; D003625:Data Collection; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D006801:Humans; D008094:Lithium / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D018692:Antimanic Agents; D008094:Lithium; D002118:Calcium