Lithium and Chronic Kidney Disease (CKD): To Stop or Not to Stop?

Lithium and Chronic Kidney Disease (CKD): To Stop or Not to Stop?

The management of Lithium in patients with declining renal function remains one of the most complex “risk-benefit” balances in modern medicine.

Lithium is the “gold standard” first-line mood stabiliser for Bipolar Affective Disorder (BPAD) and is uniquely proven to reduce suicide risk. However, long-term use is associated with a 2.5-fold increased risk of developing Chronic Kidney Disease (CKD).

The central dilemma: Stopping Lithium may save the kidneys but trigger a life-threatening psychiatric relapse.

1. The Mechanism: How Lithium Affects the Kidneys

Lithium is primarily excreted by the kidneys. Over years of therapy, it can cause Chronic Tubulo-interstitial Nephritis.

• Early Sign: Impaired concentrating ability (Polyuria and Polydipsia).

• Progression: A gradual decline in the Glomerular Filtration Rate (eGFR).

• Risk: While the risk of reaching End-Stage Renal Disease (CKD Stage 5) is relatively low (approx. 0.5%–1%), it is significantly higher than in the general population.

2. Clinical Decision Framework (2026 Update)

Based on the seminal decision analysis by Werneke et al. and more recent reviews (Velani, 2023), the consensus suggests that Lithium should not be stopped automatically just because eGFR declines.

Management by CKD Stage:

The “Relapse Caveat”: If a patient has a history of severe, life-threatening mania or treatment-resistant depression, many clinicians recommend monitored continuation even into Stage 4, provided the patient and family consent to the risks.

3. Strategies for Continued Lithium Use

If the decision is made to continue Lithium in the presence of CKD, the following “Renal-Protective” measures must be taken:

• Minimum Effective Dosing: Aim for the lowest therapeutic trough level (often 0.4–0.6 mmol/L).

• Once-Daily Dosing: Evidence suggests that a single evening dose is less “toxic” to the renal tubules than divided doses.

• Avoid the “Triple Whammy”: Be extremely cautious with drugs that acutely reduce eGFR, specifically:

  • NSAIDs (e.g., Ibuprofen, Naproxen)

  • ACE Inhibitors / ARBs (e.g., Ramipril, Losartan)

  • Diuretics (especially Thiazides)

• Strict Monitoring: Increase the frequency of eGFR and Lithium level checks (e.g., every 2–3 months).

4. How to Safely Discontinue Lithium

If the renal risk is deemed too high, Lithium must be stopped with extreme care to prevent “rebound mania.”

1. Taper Slowly: The reduction should take place over 1 to 3 months.

2. Cross-Taper: Introduce an alternative mood stabiliser (e.g., Valproate, Quetiapine, or Lamotrigine) during the taper if appropriate.

3. High-Vigilance Period: Monitor the patient bi-weekly during the taper and for at least 3 months after the final dose for signs of relapse.

5. When to Refer to Nephrology

A referral to a Renal specialist is recommended if:

• The eGFR is dropping by >5 ml/min/year.

• The patient reaches CKD Stage 4.

• There is heavy proteinuria (protein in the urine), which may suggest a diagnosis other than lithium-induced nephritis.

Summary: A Shared Decision-Making Process

The decision to continue or stop Lithium is not purely a medical one; it is a quality-of-life choice.

• Education: Patients and families must be briefed on the dual risks: renal failure vs. psychiatric relapse.

• Documentation: Clear documentation of the multidisciplinary discussion (Psychiatry, Pharmacy, and GP) is essential for medicolegal safety.