Intended for healthcare professionals

Practice Practice Pointer

Lithium and chronic kidney disease

BMJ 2009; 339 doi: (Published 03 July 2009) Cite this as: BMJ 2009;339:b2452

Li-fe or death of the collecting duct?

Kripalani and colleagues point out the necessary monitoring and
required vigilance for patients receiving treatment with lithium, to
ensure renal toxicity is not missed 1.

It is worth noting that nephrogenic diabetes insipidus (NDI) is the most
common “renal” side effect of this drug, causing reduced concentrating
ability in over half of patients and leading to significant polyuria in
around one fifth of patients 2. These urinary concentration defects are
not always reversible upon stopping lithium.

Lithium is toxic to the principal cells of the collecting duct cells
(which are responsible for regulating final urinary concentration).
Lithium enters and accumulates in these cells from the filtrate via apical
amiloride sensitive ENaC channels. Given this known mechanism, amiloride
treatment may be recommended as a specific therapy for lithium induced
polyuria and NDI 3. Whether the progressive renal impairment, seen with 10
-20 years of lithium treatment, is secondary to this collecting duct
toxicity alone and can therefore be largely prevented by amiloride,
remains to be determined 4.

1. Kripalani M, Shawcross J, Reilly J, Main J. Lithium and chronic
kidney disease. Bmj 2009;339:b2452.

2. Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment
of renal dysfunction associated with chronic lithium therapy. Am J Kidney
Dis 1987;10(5):329-45.

3. Batlle DC, von Riotte AB, Gaviria M, Grupp M. Amelioration of polyuria
by amiloride in patients receiving long-term lithium therapy. N Engl J Med

4. Grunfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev
Nephrol 2009;5(5):270-6.

Competing interests:
None declared

Competing interests: No competing interests

17 July 2009
John A Sayer
Senior Clinical Lecturer in Nephrology
Institute of Human Genetics, International Centre for Life, Newcastle University, NE1 3BZ, UK