Is Lithium Bad for Your Kidneys?

Lithium can harm the kidneys, but for most people taking it, the damage stays mild and develops slowly over years or decades. The most frequent kidney effect is a reduced ability to concentrate urine, which causes excessive thirst and frequent urination. A smaller fraction of long-term users see a meaningful decline in overall kidney filtration, and progression to kidney failure requiring dialysis is rare. The story is more nuanced than a simple yes or no, because the risk depends heavily on how long you take lithium, what your blood levels run, and how closely your kidney function is tracked.

The Most Common Kidney Problem

The kidney issue that shows up earliest and most often in lithium users is called nephrogenic diabetes insipidus, or NDI. Despite the name, it has nothing to do with blood sugar. What happens is that your kidneys lose some of their ability to pull water back from urine before it leaves your body. The result is dilute, high-volume urine and persistent thirst. Some people produce several liters of urine a day. NDI can appear within weeks of starting lithium and affects a substantial portion of long-term users.

At the cellular level, lithium reduces the abundance of a water channel called aquaporin-2 (AQP2) in the cells lining the kidney’s collecting ducts. These channels are how the kidney normally reabsorbs water in response to antidiuretic hormone. Lithium lowers AQP2 levels by suppressing its gene transcription, and separately, prostaglandins produced in response to lithium accelerate the breakdown of whatever AQP2 protein remains.¹ Lithium enters the principal cells of the collecting duct through the epithelial sodium channel (ENaC), which is the same channel that moves sodium.² Once inside, it disrupts the signaling that normally keeps those water channels in place.

Early on, this concentrating defect is largely functional and reversible if lithium is stopped. Over years of treatment, though, it can become structural, meaning the kidney tissue itself changes in ways that are harder to undo.³ That distinction between early reversibility and late permanence is one reason regular monitoring matters from the start.

What Lithium Does to Kidney Tissue

When pathologists examine kidney biopsies from people on long-term lithium, the pattern they see is distinctive. The damage is concentrated in the tubules and the tissue between them (the interstitium), not the glomeruli, which are the tiny filtering units. Biopsies typically show interstitial fibrosis, tubular atrophy, and small cysts forming in and around the damaged tubules.⁴ The glomeruli tend to be relatively spared, at least in early and moderate stages.⁵

This pattern matters because it means lithium nephropathy looks different from many other common causes of chronic kidney disease, which typically start by damaging the glomeruli. On imaging, the microcysts that form in lithium-treated kidneys are sometimes visible on MRI or ultrasound, and they can serve as a clue that lithium is the culprit when kidney function is declining.⁶

Animal research has added another layer: genetic background appears to influence how severely the kidneys respond. A study across multiple mouse strains found that lithium caused interstitial fibrosis and tubular atrophy in some strains but not others, and that the drug actually lowered a marker of glomerular damage in several strains.⁷ This hints that some people may be genetically more vulnerable to lithium’s kidney effects than others, though practical genetic tests for this do not yet exist.

How Quickly Does Kidney Filtration Decline

Beyond the concentrating defect, the bigger clinical concern is whether lithium causes a progressive drop in overall kidney filtration, measured by the estimated glomerular filtration rate (eGFR). The evidence consistently says it does, but the pace varies.

A large study of lithium users found that eGFR declined by about 0.7% per year of age and about 0.9% per year of lithium treatment, with women losing filtration about 19% faster than men.⁸ A Dutch 10-year cohort study confirmed that higher lithium blood concentrations were linked to steeper eGFR drops, and that longer duration of lithium use independently predicted a faster annual decline.⁹

To put those numbers in context, everyone’s eGFR declines with age regardless of medication. The concern with lithium is that it stacks additional decline on top of normal aging. A cross-sectional study found that about half of patients treated with lithium for more than 20 years had an eGFR below 60, which is the threshold for stage 3 chronic kidney disease. The median time on lithium before reaching that threshold was roughly 25 years.¹⁰ Another study found that about a third of patients on lithium for 10 to 29 years showed signs of chronic kidney problems, though only around 5% fell into the severe category.¹¹

How Often Does It Progress to Serious Kidney Disease

Progression to end-stage renal disease requiring dialysis is uncommon. One cohort study of lithium-treated patients documented zero cases of end-stage disease (eGFR below 15) over the study period.¹² But uncommon does not mean zero. A population-based study from The Lancet Psychiatry found that roughly 10% of lithium users developed stage 3 or higher chronic kidney disease, compared with about 3% of a control group not on lithium. That translated to about double the risk after adjusting for age, sex, and other health conditions.¹³

Age makes a big difference to absolute risk. A large retrospective cohort found that for lithium users under 50, the added risk of outright renal failure was tiny, roughly one extra case per 660 patients treated. For those over 50, that jumped to roughly one extra case per 44 patients.¹⁴ So the kidney risk of lithium is heavily age-dependent, a reality that factors into treatment decisions especially for people who start lithium later in life or continue it into old age.

Among the small number of patients who do reach end-stage disease and need dialysis, the human toll is real. A qualitative study of patients with lithium-induced kidney failure found that most struggled emotionally with the fact that their treatment had caused the damage. Many described painful procedures and the time burden of dialysis. Yet most also acknowledged that lithium had been profoundly effective for their bipolar disorder, and the majority said they had adjusted to dialysis over time.¹⁵

The Risk Factors That Matter Most

Two factors dominate the research on who is most likely to develop significant kidney problems from lithium: how long you take it and how high your blood lithium levels run. The Lancet Psychiatry study broke this down sharply. Compared with controls, patients whose average lithium blood concentration was in the 0.60–0.79 mmol/L range had about triple the risk of stage 3+ chronic kidney disease, and those in the 0.80–0.99 range had roughly four times the risk. But patients averaging below 0.60 mmol/L showed no significantly increased risk at all.¹³

A review of the evidence ranked the strongest risk factors as higher serum lithium concentration and longer treatment duration, calling serious toxicity “uncommon” overall.¹⁶ Episodes of lithium overdose or toxicity also appear to be independent risk factors. One cohort study specifically identified overdoses as contributing to chronic kidney disease, underscoring the importance of dose management.¹⁷

Female sex and older age round out the list. Women tend to lose kidney filtration faster on lithium, and pre-existing medical conditions amplify the decline.⁸

Acute Kidney Injury From Lithium Toxicity

Separate from the slow, chronic kidney effects, lithium can cause sudden kidney injury when blood levels spike. This happens during lithium overdose or when something else pushes levels above the therapeutic window. Acute kidney injury from lithium toxicity is typically reversible with prompt treatment, including hemodialysis in severe cases.¹⁸

A population-based review of lithium intoxication episodes found that about a third of patients required intensive care and 13% needed hemodialysis, but there were no deaths. Kidney function after the acute episode typically returned to baseline. In many cases, the toxicity was linked to other health problems or medication interactions rather than to lithium alone.¹⁹

Drug Interactions That Raise Kidney Risk

Some commonly used medications can push lithium levels up by changing how the kidneys handle it. The main culprits are NSAIDs (ibuprofen, naproxen, and similar over-the-counter painkillers), ACE inhibitors and angiotensin receptor blockers used for blood pressure, and most diuretics (water pills).²⁰

NSAIDs are a particular concern because they are so widely available without a prescription. They reduce blood flow to the kidneys and promote the reabsorption of both sodium and lithium, which can elevate lithium blood levels above the therapeutic range.²¹ Dehydration from illness, heat, or vigorous exercise has a similar effect. Anything that reduces kidney filtration or increases sodium reabsorption can inadvertently concentrate lithium in the blood and magnify its kidney effects. If you take lithium, acetaminophen (paracetamol) is generally a safer choice for occasional pain relief.

What Happens When You Stop Lithium

A question many patients and clinicians face is whether stopping lithium can reverse or at least slow kidney decline. Recent evidence is encouraging on this front. A mirror-image study found that the average annual eGFR decline went from roughly −1.6 before stopping lithium to essentially zero afterward, and this improvement persisted over five years of follow-up. The benefit was most dramatic in patients whose kidneys were already significantly impaired: those with eGFR below 30 saw an average improvement of about 3 units per year after discontinuation.²²

Another study confirmed this pattern. Among patients with stage 3 or worse kidney disease, the large majority showed either an improvement in eGFR or at least a slower rate of decline after stopping lithium. However, a subgroup with more severely impaired kidneys (average eGFR around 32) continued to deteriorate despite discontinuation.²³ An earlier cross-sectional study found no difference in kidney decline between those who stopped lithium and those who continued once eGFR had already dropped below 45.¹⁰

The upshot: stopping lithium helps most, and helps the most dramatically, when kidney function has not yet fallen too far. Once the damage is advanced, the structural changes in the tubules and interstitium may be self-sustaining regardless of whether lithium is still present. This creates a clinical tension: stopping lithium removes the kidney insult but also removes a medication that, for many patients, is uniquely effective at preventing manic and depressive episodes.

Amiloride as a Protective Strategy

Because lithium enters kidney cells through the epithelial sodium channel, the diuretic amiloride, which blocks that channel, has been studied as a way to reduce lithium’s kidney effects. In a randomized trial, amiloride improved the kidney’s concentrating ability and increased AQP2 levels in lithium-treated patients.²⁴ An earlier study showed that amiloride reduced daily urine volume from about 4.7 liters to 3.1 liters and raised urine concentration, with the effect sustained over six months without significantly changing lithium blood levels or potassium.²⁵

Amiloride is not a standard part of lithium regimens everywhere, but some clinicians add it when patients develop bothersome polyuria. Unlike thiazide diuretics (another option sometimes used for lithium-induced NDI), amiloride does not raise the risk of lithium toxicity by depleting sodium. It is one of the few interventions that targets the actual mechanism by which lithium enters kidney cells.

How Lithium Compares to Other Mood Stabilizers

Part of the anxiety around lithium and kidneys comes from how often the risk is discussed in clinical settings compared with alternatives. A large Swedish study directly compared kidney outcomes between lithium and valproate, another common mood stabilizer. The 10-year risk of chronic kidney disease was about 8.4% in the lithium group and 8.2% in the valproate group, with no statistically significant difference. The study also found no difference in the risk of acute kidney injury, albuminuria, or the annual rate of eGFR decline between the two drugs.²⁶

This does not mean lithium is free of kidney risk, but it does put the risk in perspective. People with bipolar disorder who are not on lithium also show higher-than-average rates of kidney problems, possibly related to the illness itself, other medications, or associated conditions like diabetes and hypertension. Disentangling lithium’s direct effects from these background factors is one of the persistent challenges in the field.³

Monitoring and When to See a Nephrologist

Clinical guidance calls for a baseline kidney function test (eGFR) before starting lithium and regular monitoring during treatment. The exact frequency varies by guideline, but most clinicians check at least every six months once the patient is on a stable dose, and more frequently in the first year or if there are risk factors.²⁷

If eGFR drops rapidly or falls below 60, guidelines recommend a nephrology consultation. The decision about whether to stop lithium is not straightforward, because the mental health risks of discontinuation can be severe. A review of the evidence noted that it remains unclear when cessation is appropriate, given that kidney disease can continue to progress even after lithium is stopped, and that the morbidity of uncontrolled bipolar disorder is itself substantial.²⁸ In practice, clinicians and patients weigh whether lithium has been uniquely effective, whether alternative mood stabilizers are viable, and how fast the kidneys are declining.

Lithium and Calcium Metabolism

Kidney function is not the only metabolic concern with long-term lithium use. Lithium can also disrupt calcium balance by causing hyperparathyroidism, a condition where the parathyroid glands release too much parathyroid hormone, driving up blood calcium levels. This happens because lithium shifts the set point at which the calcium-sensing receptor signals the parathyroid glands to stop secreting hormone.²⁹ Chronic high calcium can itself damage the kidneys, so this creates a secondary pathway by which lithium may contribute to kidney dysfunction beyond its direct tubular effects. Routine monitoring of calcium levels is part of the standard workup for lithium-treated patients, and catching hyperparathyroidism early can prevent this compounding effect.

A cohort study explicitly identified hyperparathyroidism and hypercalcemia as outcomes associated with longer lithium treatment duration, reinforcing the link between cumulative lithium exposure and disrupted calcium signaling.¹⁷ If your calcium levels are creeping up on lithium, that is worth flagging with your prescriber even if your kidney numbers still look fine.

1
PubMed. Lithium reduces aquaporin-2 transcription independent of prostaglandins
2
PubMed. Amiloride blocks lithium entry through the sodium channel thereby attenuating the resultant nephrogenic diabetes insipidus
3
PubMed. Lithium and the kidney: an updated review
4
PubMed Central. MRI findings in chronic lithium nephropathy: a case report
5
PubMed. Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal
6
Tzu Chi Medical Journal. Pathology Page Chronic lithium nephropathy
7
PubMed. Genetic background determines renal response to chronic lithium treatment in female mice
8
PubMed Central. Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters
9
PubMed Central. A Significant Decline of Glomerular Filtration Rate in the Majority of Long‐Term Lithium Users: Results of a Dutch Prospective 10‐Year Cohort Study
10
PubMed Central. Renal function during long-term lithium treatment: a cross-sectional and longitudinal study
11
PubMed. Effects of 10 to 30 years of lithium treatment on kidney function
12
PubMed Central. Chronic kidney disease in lithium-treated patients, incidence and rate of decline
13
The Lancet Psychiatry. Risk of chronic kidney disease in people receiving lithium therapy: a retrospective population-based cohort study
14
PLoS ONE. Renal Failure in Lithium-Treated Bipolar Disorder: A Retrospective Cohort Study
15
PubMed Central. The perspectives of patients with lithium-induced end-stage renal disease
16
PubMed Central. What we need to know about the effect of lithium on the kidney
17
PubMed Central. Long-term lithium therapy and risk of chronic kidney disease, hyperparathyroidism and hypercalcemia: a cohort study
18
PubMed. Lithium intoxication associated with acute renal failure
19
PubMed Central. Lithium intoxication: Incidence, clinical course and renal function – a population-based retrospective cohort study
20
PubMed Central. Lithium therapy and its interactions
21
Revista de Psiquiatria Clínica. Lithium interactions with non-steroidal anti-inflammatory drugs and diuretics – A review
22
PubMed Central. Kidney function decline improves after lithium discontinuation
23
PubMed. Renal function after withdrawal of lithium
24
PubMed Central. Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride
25
PubMed. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy
26
PubMed Central. Absolute and Relative Risks of Kidney Outcomes Associated With Lithium vs Valproate Use in Sweden
27
PubMed Central. Key questions on the long term renal effects of lithium: a review of pertinent data
28
PubMed Central. Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification
29
PubMed Central. Lithium-induced Hyperparathyroidism and Hypercalcemia