Lithium continues to be a primary line therapy for temper circumstances comparable to bipolar dysfunction, and rightfully so, because it continues to be unmatched in its potential to stabilise moods (see, for instance, this latest weblog about decreased hospitalisations being related to Lithium use).
Nonetheless, its unfavorable influence on kidneys is nicely documented and, in the event you belong to any critical psychological sickness help group, you’ll know an individual or three whose kidneys have been impacted by lithium. And so, as sufferers, we frequently ask ourselves “kidneys or psychological well being?” And this isn’t an arbitrary query to these of us who reside with a critical psychological sickness. We aren’t the rooster whose contribution to breakfast is an egg; we’re the pig whose contribution to breakfast is a sausage. We now have critical pores and skin within the recreation!
Inching us ahead on this quest for solutions, van der Aa et al. (2026) sought to quantify how lithium impacts kidney operate over ten years.
Strategies
This research was based mostly within the Netherlands, and the factors for inclusion had been:
- sufferers residing with a temper dysfunction,
- have been prescribed lithium,
- had been energetic within the medical system, and
- had a follow-up of greater than a 12 months.
They ended up having 196 sufferers of which 42% had been male, with a imply age of 51.1 years at begin. The measurements for use had been based mostly on estimated glomerular filtration price (eGFR: a key indicator of how nicely the kidneys are filtering waste from the blood) and the Continual Kidney Illness Epidemiology Collaboration (CKD-EPI) equation.
The investigators tracked:
- the size of time {that a} affected person was on lithium remedy,
- ongoing blood serum concentrations,
- whether or not the affected person was on every other drugs (comedication), and
- whether or not any sufferers stopped lithium in the course of the ten 12 months interval.
Sufferers who stopped lithium in the course of the research had been monitored for any additional decline in eGFR.
The researchers had their work reduce out for them. Sufferers who stopped utilizing lithium had been in contrast towards these sufferers who continued lithium therapy. And, sufferers who stopped lithium therapy as a result of eGFR decline had been in contrast towards sufferers who ceased lithium therapy for different causes. Drugs identified to affect eGFR decline besides lithium had been rigorously excluded. The analysis crew then tracked how lithium was used, the dose and the impact of discontinuation on kidney operate.
Outcomes
The median comply with up was 8.8 years and the investigators discovered that there was a major decline (p < 0.001) in eGFR at inclusion versus the eGFR at comply with up. The trajectories of eGFR in most sufferers had been linear nevertheless eGFR trajectories weren’t linear in sufferers who had been both pregnant or admitted in medical hospitals. And so sufferers’ outcomes whereas hospitalised and when pregnant had been excluded. The median decline in eGFR in sufferers was 0.79 mL/min/1.73 m2 per 12 months; 11% of the contributors had > 2.5 mL/min/1.73 m2 eGFR decline per 12 months.
The outcomes confirmed a relationship between lithium focus and eGFR decline when managed for age, intercourse and length of lithium remedy at baseline. Moreover, there was a major affiliation between median length (which was 16 years) and eGFR discount. Different drugs identified to extend the danger of kidney decline weren’t discovered to have a major affiliation with eGFR decline when the outcomes had been corrected for intercourse and age.
Thirty 9 of the 196 sufferers stopped lithium therapy. In 18 cases the explanations for discontinuation had been as a result of documented unwanted effects together with kidney decline, nephrotoxicity (kidney injury), complaints of polyuria (extreme urination related to lithium utilization) or psychiatric remission. In three different cases the explanations for discontinuation weren’t documented. The paper doesn’t appear to account for the remaining 18 discontinuations.
The decline of eGFR noticed in long run lithium customers was greater than the decline noticed within the common Netherlands inhabitants, suggesting that the elevated decline was linked to the long run use of lithium. The analysis crew additionally famous that earlier than ceasing lithium, the sufferers who stopped utilizing lithium skilled comparable decline in eGFR to those that stayed on lithium in the course of the tenure of the research. Of the 39 sufferers who stopped lithium, solely 33 had comply with up info which was used to find out this discovering. Though the decline slowed (from 1.3 to 0.27 mL/min/12 months) in those that ceased lithium consumption, it was not vital for the needs of this research when tracked throughout this ten 12 months interval. One other attainable purpose for them concluding that there was no vital slowing in kidney decline is that they’d a small variety of contributors of their research after which a good smaller variety of contributors stopping lithium. It is also attainable that they didn’t see statistically vital enchancment as a result of they may not monitor the long run variations.
Furthermore the analysis crew discovered that there was a major relationship between greater serum concentrations and eGFR decline, that means there may be an affiliation between lithium therapy and kidney operate decline. The crew discovered no proof that comedication between lithium and nephrotoxic drugs might be worsening the decline of kidney operate, however the jury continues to be out on this one.
Conclusions
The authors concluded:
This research gives additional proof that eGFR decline happens in most long-term lithium customers. Of this cohort, 59% of the contributors had sooner eGFR decline than the imply decline within the common inhabitants. Lithium publicity, quantified as imply serum lithium focus, might be a contributing issue on this decline.
Strengths and limitations
I agree with the analysis crew that their research was necessary as a result of they’d lengthy comply with up time and their cohort had been on lithium for a protracted interval, they may use the outcomes from bi-annual monitoring of sufferers who’re on lithium to assemble a trajectory of their kidneys.
The research additionally had numerous limitations beginning with the truth that, as an observational research, it’s not attainable to attract conclusions a few causal relationship between lithium and kidney operate. There are additional limitations of the research that I discovered to be necessary. The primary is that the researchers couldn’t confirm whether or not sufferers had waited 12 hours after lithium consumption earlier than taking lithium measurements and this might have influenced the outcomes of the serum lithium focus captured. The second is that the researchers predominantly relied on medical studies after the baseline to find out comedication. We simply hope there was no attrition of knowledge because it was transferred from affected person to the physician after which physician to the researcher. I believe there might have been simply because consultations are so brief that there is no such thing as a time to relay the whole lot to the physician. So you permit with the identical prescription for drugs that fill your medication cupboard, taken on an “as and once I see mandatory foundation”.
Different research have hypothesised that the presence of comorbidities (hypertension, diabetes and so forth) might be a attainable purpose for the eGFR decline (Clos et al, 2015), nevertheless this research didn’t have comorbidities as a variable so we can not draw any conclusions on that chance. We hope to see researchers together with these illness variables in future research. van der Aa et al. additionally had a restricted variety of nephrotoxic drugs to have the ability to conclusively decide whether or not they might be the precise reason for the eGFR decline. The analysis crew recognises that one of many research limitations, like different research investigating lithium’s influence on the kidneys, was it didn’t have a big sufficient cohort. This makes it more durable to trust in its findings, which is regarding given the seriousness of those unwanted effects and the significance of lithium as a therapy.
Implications for apply
I discovered the research spectacular in that it was sturdy in its design and subsequently meaningfully contributed to the information across the influence of lithium use on the kidneys. It additionally adopted the sufferers as a substitute of amassing knowledge after which working backwards, which allowed them to additionally see what occurs to sufferers who keep on lithium versus those that cease lithium therapy.
This research highlights that we don’t but know whether or not stopping lithium as soon as kidney operate is considerably decreased is useful. And what of the temper instability that would happen because of stopping lithium therapy?
Though most likely seen in apply, these investigators add to the physique of data supporting that clinicians ought to attempt to pursue the bottom lithium focus mandatory to attain temper stability and common optimum medical outcomes. van der Aa et al. help the monitoring of lithium concentrations as per the present tips and measuring kidney operate in a way that’s individualised. Importantly, they make no advice on the plan of action to be taken when people who find themselves taking lithium start experiencing kidney decline.
The analysis crew has many suggestions for future research together with potential designs that search to seize the biomarkers that may work as surrogate measures. These surrogate measures can be utilized to seize future kidney operate decline thereby eradicating the necessity for expansive decade lengthy medical research. These can be used to substantiate whether or not there’s a level of no return in relation to kidney decline.
Now keep in mind, there are normally two individuals within the psychiatric room throughout session. One (the practitioner) ought to take care to make use of finest apply when prescribing the dose of lithium to be taken by the affected person. The opposite (the affected person) ought to do not forget that they’re the proverbial pig and never the rooster, so it’ll do us a complete lot of excellent to be our personal finest advocate in that consulting room.
Assertion of pursuits
The writer of this weblog (Nomhle Nhlapho) declares that she stopped lithium inside 3-6 months of beginning lithium therapy as a result of unwanted effects from the medicine.
Edited by
Edited by Simon Bradstreet.
Hyperlinks
Major paper
van der Aa, M. J., Zittema, D., Doornebal, J., Hartong, E. G. T. M., Bisseling, E. M., Dammers, J., Klumpers, U. M. H., Kerckhoffs, A. P. M., Kupka, R. W., & Nijenhuis, T. (2026). A Important Decline of Glomerular Filtration Charge within the Majority of Lengthy-Time period Lithium Customers: Outcomes of a Dutch Potential 10-12 months Cohort Research. Bipolar Issues, 28(2), e70082.
Different references
Clos, P. Rauchhaus, A. Severn, L. Cochrane, and P. T. Donnan. (2015). Lengthy-Time period Impact of Lithium Upkeep Remedy on Estimated Glomerular Filtration Charge in Sufferers With Affective Issues: A Inhabitants-Based mostly Cohort Research, Lancet Psychiatry 2, no. 12: 1075–1083
