SEARCHCOHORTnephrology, nutrition

cohort·nephrology, nutrition, micronutrients, minerals, observational study·PMC10387402

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

Nephrology Dialysis Transplantation · 10 authors, 11 centres

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TL;DR

This observational study of 642 stable kidney transplant recipients found that higher urinary lithium excretion, reflecting higher dietary lithium intake, was associated with a lower risk of graft failure, kidney function decline, and all-cause mortality over a median of 5.3 years.

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This prospective cohort study measured urinary lithium excretion in 642 stable kidney transplant recipients (KTRs) to assess its association with long-term outcomes. During a median follow-up of 5.3 years, 79 KTRs developed graft failure and 127 developed kidney function decline. Higher urinary lithium excretion was significantly associated with a lower risk of graft failure (HR per doubling 0.54) and kidney function decline (HR per doubling 0.73), associations that persisted after adjustment for confounders. Higher excretion was also associated with reduced all-cause mortality (HR 0.64). The authors note that the protective association was stronger in subgroups not using proliferation inhibitors and with lower baseline eGFR. Implications suggest dietary lithium intake may be a modifiable factor for improving graft outcomes, though the underlying mechanisms require further investigation.

STUDY TYPE

cohort

SPECIALTY

nephrology

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ORIGINAL PAPER

PMC10387402

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

Nephrology Dialysis Transplantation

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ABSTRACT

ABSTRACT Background Long-term high-dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies have 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 (KTRs). Graft failure was defined as the start of dialysis or retransplantation and kidney function decline was defined as a doubling of serum creatinine. Results The median urinary lithium excretion was 3.03 μmol/24 h [interquartile range (IQR) 2.31–4.01]. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3 years (IQR 4.5–6.0), 79 (12%) KTRs developed graft failure and 127 (20%) KTRs developed kidney function decline. Higher urinary lithium excretion was associated with a lower risk of graft failure {hazard ratio [HR] per doubling 0.54 [95% confidence interval (CI) 0.38–0.79]} and kidney function decline [HR per doubling 0.73 (95% CI 0.54–0.99)]. These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was a significant effect modification with the use of proliferation inhibitors ( P = .05) and baseline estimated glomerular filtration rate (eGFR; P < .001), with higher urinary lithium excretion being more protective in KTRs not using proliferation inhibitors and in KTRs with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with a reduced risk of all-cause mortality [HR 0.64 (95% CI 0.49–0.83); P = .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. Trial registration https://clinicaltrials.gov/ct2/show/NCT02811835 Keywords: graft failure, kidney transplant recipients, lithium, mortality

CITATION EXPORT

Adrian Post, Daan Kremer, Dion Groothof et al.. Dietary lithium intake, graft failure and mortality in kidney transplant recipients. Nephrology Dialysis Transplantation. (2022). https://doi.org/10.1093/ndt/gfac340

AUTHORS

10 · 11 CENTRES

Adrian Post, Daan Kremer, Dion Groothof, Ulrike Seidel, Patricia Huebbe, Casper F M Franssen, Ido P Kema, Kai Lüersen, Gerald Rimbach, Stephan J L Bakker

1 Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
2 Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
3 Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
4 Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany
5 Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany
6 Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
7 Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
8 Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany
9 Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany
10 Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
11Prinicipal Investigator of the TransplantLines cohort studies