Dietary lithium intake, graft failure and mortality in kidney transplant recipients

BACKGROUND & AIMS: Long-term high dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies revealed that low amounts of lithium are beneficial for the kidney when it is damaged by exposure to nephrotoxic compounds, inflammation, or oxidative stress. This study aimed to investigate whether urinary lithium excretion, reflecting dietary lithium intake, is associated with adverse long-term kidney graft outcomes and patient survival.

METHODS: Urinary lithium concentration was measured using inductively coupled plasma-mass-spectrometry in 642 stable kidney transplant recipients. Graft failure was defined as start of dialysis or re-transplantation, and kidney function decline was defined as doubling of serum creatinine.

RESULTS: Median [interquartile range] urinary lithium excretion was 3.03 [2.31-4.01] μmol/24 h. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3 [4.5-6.0] years, 79 (12%) KTR developed graft failure and 127 (20%) KTR developed kidney function decline. Higher urinary lithium excretion was associated with lower risk of graft failure (hazard ratio [95% confidence interval]: 0.54 [0.38-0.79] per log2 μmol/24 h) and kidney function decline (HR [95% CI]: 0.73 [0.54-0.99] per log2 μmol/24 h). These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was significant effect modification by use of proliferation inhibitors (P = 0.05) and baseline eGFR (P < 0.001), with higher urinary lithium excretion being more protective in KTR not using proliferation inhibitors and in KTR with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with reduced risk of all-cause mortality (HR [95% CI]: 0.64 [0.49-0.83]; P = 0.001).

CONCLUSION: Dietary lithium intake may be a potentially modifiable-yet rather overlooked-risk factor for adverse long-term kidney graft outcomes and patient survival.