Potential interaction between high protein intake and lithium exposure in renal dysfunction: a case report

Background

Lithium remains a cornerstone in the long-term treatment of mood disorders, but chronic exposure may impair renal concentrating ability, described as nephrogenic diabetes insipidus or arginine vasopressin resistance, and may contribute to chronic tubulointerstitial nephropathy. Lithium-associated renal dysfunction usually develops gradually; however, the contribution of patient-specific behavioral and dietary factors is poorly characterized. High-protein intake can increase glomerular hyperfiltration, urea generation, and osmotic load, which may be clinically relevant in patients with pre-existing tubular vulnerability. This case aimed to describe the longitudinal renal course of a lithium-treated patient with psychosis-driven extreme protein intake and to evaluate whether dietary modification was associated with renal improvement.

Case Presentation

We report a 29-year-old male with schizoaffective disorder who consumed an extreme high-protein diet for approximately two years in the context of psychotic delusions. His daily intake reportedly included 800–1000 g of meat, protein-enriched milk, and high caffeine consumption, with estimated protein intake exceeding 4 g/kg/day. Serial laboratory data were retrospectively reviewed from clinical records. During the early phase of this diet and lithium maintenance, estimated glomerular filtration rate (eGFR) appeared preserved at 90–99 mL/min/1.73 m², while urine specific gravity remained fixed around 1010, consistent with persistent isosthenuria and impaired urinary concentrating ability. Renal function then showed a gradual decline, with eGFR decreasing to 83 mL/min/1.73 m² in May 2023, 74 mL/min/1.73 m² in July 2023, and 71 mL/min/1.73 m² in October 2023. In early 2024, renal dysfunction became more pronounced, reaching an eGFR of 46 mL/min/1.73 m² with serum creatinine of 1.96 mg/dL. Serum lithium concentrations ranged approximately between 0.42 and 1.2 mEq/L during follow-up.

Following nephrological evaluation, daily protein intake was restricted to approximately 75 g/day, corresponding to about 1 g/kg/day and consistent with guideline-based dietary reduction in chronic kidney disease risk management. After this intervention, eGFR partially improved to 68 mL/min/1.73 m², while persistent isosthenuria continued, suggesting residual tubular concentrating impairment despite functional recovery. Discontinuation of lithium was considered because of renal risk; however, attempted cessation was followed by severe depressive relapse with psychotic features. Therefore, lithium was continued in a long-acting formulation with close psychiatric and nephrological monitoring. The patient remained clinically stable under modified protein intake and continued laboratory follow-up.

Conclusions

This case suggests that extreme dietary protein exposure may modify the clinical trajectory of lithium-associated renal dysfunction. The temporal association between protein restriction and partial eGFR recovery highlights a potentially modifiable component superimposed on persistent tubular dysfunction. These observations support systematic assessment of dietary habits and other lifestyle factors in lithium-treated patients with renal decline. A multidisciplinary, patient-centered approach may help balance renal risk with the psychiatric need for continued lithium therapy in selected complex cases.

Keywords: Lithium; High-protein diet; Chronic kidney disease; Tubulointerstitial nephropathy; Mood Disorders; Nephrogenic diabetes insipidus; Psychosis.

References

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