Lithium side effects (kidney)?

Question

Lithium (taken as a mood stabilizer) can lead to renal problems in patients, especially those taking it long-term. How prevalent are these side effects and how are they managed - for example, stopping to take lithium, taking other medication alongside lithium?

Answer 1

According to the UpToDate literature, adverse renal effects are statistically-associated with chronic lithium therapy. The main pathological feature involves chronic tubulointerstitial nephropathy causing symptomatology consistent with a nephrogenic diabetes insipidus (nDI) syndrome. A small-%age of patients will progress to end-stage renal disease (ESRD) from longterm lithium-associated therapy. Lithium-mediated injury implicates aquaporin-2 water channels (AQP2) in collecting duct segments that are under the influence of antidiuretic hormone (ADH) for homeostatic control. Resistance to ADH activity is associated with lithium accumulation in the distal nephron and impairs water permeability for reabsorption into the collecting ducts, leading to the symptoms/signs of DI (ex., excessive water secretion in urine, serum hyper-osmolarity)

The treatment of nDI depends on the occurrence and severity of symptoms, including changes in volume status/osmotic balance, and electrolyte/solute imbalances. Nephrogenic differs from central DI in that hypothalamic-ADH secretion is decreased in the latter condition; normal ADH levels are expected for nDI in that the pathology involves resistance/impairment at nephron-receptor sites. Thus, treatment with a synthetic analogue of ADH, like desmopressin, may not be as effective for nDI as serum ADH values can remain within a normal range. However, I have not looked much into the literature for ADH replacement in the setting of nDI. Otherwise, cessation of lithium treatment to arrest the pathogenesis of nephropathy seems reasonable. There are other psychopharmacological options that are effective for affective/mood disorders, like (1) anticonvulsants (ex. carbamazepine, lamotrigine, and valproic acid), (2) atypical antipsychotics/neuroleptics (ex., olanzepine, risperidone), and (3) antidepressants (ex., SSRIs, SNRIs).