Kidneys are uncomplaining. They lose function gradually, often without symptoms, until quite a lot of damage has accumulated. For people taking certain psychiatric medications long-term — lithium first among them, but also clozapine and several others — keeping a quiet eye on kidney function is one of the highest-value habits in maintenance care. The labs are simple, the cost is low, and the early warning they give can change a treatment plan before damage becomes permanent.
Lithium and (less commonly) clozapine can affect the kidneys over years; an annual eGFR and urine test catches problems early and almost always allows for adjustments that protect long-term function.
The basics: how doctors measure kidney function
Three numbers matter most:
- Serum creatinine — a waste product the kidneys filter out. High numbers suggest reduced filtering.
- eGFR (estimated glomerular filtration rate) — calculated from creatinine, age, and sex. Normal is roughly above 90 mL/min/1.73m². Numbers under 60 sustained for three months define chronic kidney disease (CKD).
- Urine albumin-to-creatinine ratio (UACR) — detects small amounts of protein leaking into urine, often the earliest sign of kidney trouble.
The National Kidney Foundation has clear plain-language explanations of all of these.
Lithium and the kidney
Lithium is a remarkably effective mood stabiliser and is sometimes used as augmentation in schizoaffective disorder or treatment-resistant schizophrenia. It is also the psychiatric medication with the clearest long-term effect on the kidneys. Two main concerns:
1. Nephrogenic diabetes insipidus (NDI)
Lithium can blunt the kidneys' response to antidiuretic hormone, leading to large volumes of dilute urine and matching thirst. People may notice they are constantly drinking water and waking several times at night to urinate. This can develop within months of starting lithium and is often (though not always) reversible if lithium is reduced or stopped.
2. Chronic kidney disease
After many years (typically 10+) of lithium use, a slow decline in eGFR is common. A 2010 meta-analysis in The Lancet (McKnight et al.) found a small but real increased risk of reduced GFR; a minority of long-term users develop more significant CKD. Risk rises with cumulative dose, episodes of lithium toxicity, and concurrent kidney insults (dehydration, NSAIDs, contrast scans without precautions).
Practical steps for people on lithium
- Lithium level, creatinine, eGFR, calcium, and TSH every 3–6 months
- Stay well hydrated — but do not over-drink to the point of diluting your lithium level
- Avoid NSAIDs (ibuprofen, naproxen) when possible — paracetamol/acetaminophen is generally safer
- Tell any other doctor or radiologist that you are on lithium before contrast scans, surgery, or new prescriptions
- Report any sudden increase in thirst or urination promptly
Clozapine and the kidney
Clozapine has a relatively benign kidney profile compared to lithium, but a small number of cases of clozapine-induced interstitial nephritis have been reported. Most occur in the first month of treatment and present with fever, rash, and rising creatinine. The clozapine REMS monitoring system primarily watches white blood cells, but a baseline creatinine and at least annual eGFR are sensible. See clozapine side effects.
Other psychiatric medications and the kidney
- Topiramate — modest risk of kidney stones; encourage hydration.
- Gabapentin and pregabalin — eliminated by the kidneys; doses should be reduced as eGFR falls.
- SGLT2 inhibitors (sometimes used for antipsychotic-related diabetes) — actually protect the kidneys in CKD, but require monitoring.
- NSAIDs — not psychiatric, but very commonly used for akathisia or general aches; reduce kidney perfusion and worsen lithium toxicity risk.
What an eGFR number means
- ≥ 90 — normal (assuming no protein in urine)
- 60–89 — mildly reduced (only a problem if combined with protein in urine or other findings)
- 45–59 — moderately reduced (CKD stage 3a) — usually triggers a conversation about medication choices
- 30–44 — moderately to severely reduced (stage 3b)
- 15–29 — severely reduced (stage 4) — usually a nephrology referral
- < 15 — kidney failure (stage 5)
A single low number is not a diagnosis; CKD requires findings sustained over three months.
You have signs of lithium toxicity (coarse tremor, slurred speech, confusion, vomiting, severe diarrhoea), reduced urine output, swelling of legs or face, or symptoms of severe dehydration. These need same-day medical evaluation.
Hydration: the unsung kidney protector
Most adult kidneys do well on roughly 1.5–2 litres of fluid a day, more in hot weather, exercise, or illness. Antipsychotics that cause sweating, GI upset, or — paradoxically — extreme thirst (lithium-induced NDI) make hydration harder to maintain. In summer or during stomach bugs, having a low threshold for drinking water and contacting a clinician about lithium dose adjustment is sensible.
What changes when CKD develops
Mild CKD usually does not require stopping any psychiatric medication. Decisions are highly individual and balance:
- How long you've been on the medication and how well it works
- How fast eGFR is declining
- Other contributors (blood pressure, diabetes, NSAID use)
- Available alternatives
Sometimes the right answer is to stay on lithium with closer monitoring; sometimes it is to reduce the dose; occasionally it is to switch. This is a conversation between you, your psychiatrist, and ideally a nephrologist.
The bottom line
Kidney monitoring on long-term psychiatric medication should feel routine, not anxious. Once a year, draw the labs, check the trend, and adjust if needed. The biggest risk is not having the labs done at all.
This article is for educational purposes only and is not medical advice, diagnosis, or treatment. Always consult a qualified mental health professional. If you or someone you know is in crisis, call or text 988 in the US, or your local emergency number.