Lithium continues to be a primary line remedy for temper situations equivalent to bipolar dysfunction, and rightfully so, because it continues to be unmatched in its skill to stabilise moods (see, for instance, this current weblog about lowered hospitalisations being related to Lithium use).
Nevertheless, its detrimental affect on kidneys is effectively documented and, if you happen to belong to any severe psychological sickness assist group, you’ll know an individual or three whose kidneys have been impacted by lithium. And so, as sufferers, we regularly ask ourselves “kidneys or psychological well being?” And this isn’t an arbitrary query to these of us who dwell with a severe psychological sickness. We’re not the rooster whose contribution to breakfast is an egg; we’re the pig whose contribution to breakfast is a sausage. We now have severe pores and skin within the sport!
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 primarily based within the Netherlands, and the factors for inclusion had been:
- sufferers residing with a temper dysfunction,
- have been prescribed lithium,
- had been lively within the medical system, and
- had a follow-up of greater than a yr.
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 primarily based on estimated glomerular filtration charge (eGFR: a key indicator of how effectively the kidneys are filtering waste from the blood) and the Persistent 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 medicines (comedication), and
- whether or not any sufferers stopped lithium throughout the ten yr interval.
Sufferers who stopped lithium throughout the research had been monitored for any additional decline in eGFR.
The researchers had their work minimize out for them. Sufferers who stopped utilizing lithium had been in contrast in opposition to these sufferers who continued lithium remedy. And, sufferers who stopped lithium remedy on account of eGFR decline had been in contrast in opposition to sufferers who ceased lithium remedy for different causes. Medicines 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 observe up was 8.8 years and the investigators discovered that there was a big decline (p < 0.001) in eGFR at inclusion versus the eGFR at observe 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 scientific 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 yr; 11% of the contributors had > 2.5 mL/min/1.73 m2 eGFR decline per yr.
The outcomes confirmed a relationship between lithium focus and eGFR decline when managed for age, intercourse and period of lithium remedy at baseline. Moreover, there was a big affiliation between median period (which was 16 years) and eGFR discount. Different medicines identified to extend the danger of kidney decline weren’t discovered to have a big affiliation with eGFR decline when the outcomes had been corrected for intercourse and age.
Thirty 9 of the 196 sufferers stopped lithium remedy. In 18 situations the explanations for discontinuation had been on account of documented unwanted side effects together with kidney decline, nephrotoxicity (kidney harm), complaints of polyuria (extreme urination related to lithium utilization) or psychiatric remission. In three different situations 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 related decline in eGFR to those that stayed on lithium throughout the tenure of the research. Of the 39 sufferers who stopped lithium, solely 33 had observe up info which was used to find out this discovering. Though the decline slowed (from 1.3 to 0.27 mL/min/yr) in those that ceased lithium consumption, it was not vital for the needs of this research when tracked throughout this ten yr interval. One other doable cause 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 fair smaller variety of contributors stopping lithium. It is also doable 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 big relationship between larger serum concentrations and eGFR decline, which means there’s an affiliation between lithium remedy and kidney operate decline. The crew discovered no proof that comedication between lithium and nephrotoxic medicines may very well be worsening the decline of kidney operate, however the jury remains to be out on this one.
Conclusions
The authors concluded:
This research offers 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, may very well 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 observe 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 quite a lot of limitations beginning with the truth that, as an observational research, it’s not doable to attract conclusions a couple of 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 information because it was transferred from affected person to the physician after which physician to the researcher. I think there might have been simply because consultations are so quick that there is no such thing as a time to relay every little thing to the physician. So you permit with the identical prescription for medicines that fill your drugs cupboard, taken on an “as and once I see obligatory foundation”.
Different research have hypothesised that the presence of comorbidities (hypertension, diabetes and so on) may very well be a doable cause for the eGFR decline (Clos et al, 2015), nevertheless this research didn’t have comorbidities as a variable so we can’t draw any conclusions on that risk. 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 medicines to have the ability to conclusively decide whether or not they may very well be the precise explanation for the eGFR decline. The analysis crew recognises that one of many research limitations, like different research investigating lithium’s affect on the kidneys, was it didn’t have a big sufficient cohort. This makes it tougher to trust in its findings, which is regarding given the seriousness of those unwanted side effects and the significance of lithium as a remedy.
Implications for observe
I discovered the research spectacular in that it was strong in its design and due to this fact meaningfully contributed to the data across the affect of lithium use on the kidneys. It additionally adopted the sufferers as a substitute of accumulating knowledge after which working backwards, which allowed them to additionally see what occurs to sufferers who keep on lithium versus those that cease lithium remedy.
This research highlights that we don’t but know whether or not stopping lithium as soon as kidney operate is considerably lowered is useful. And what of the temper instability that would happen on account of stopping lithium remedy?
Though most likely seen in observe, these investigators add to the physique of information supporting that clinicians ought to attempt to pursue the bottom lithium focus obligatory to attain temper stability and common optimum scientific outcomes. van der Aa et al. assist the monitoring of lithium concentrations as per the present tips and measuring kidney operate in a fashion 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 scientific research. These will also be used to substantiate whether or not there’s a level of no return with regards to kidney decline.
Now keep in mind, there are often two folks within the psychiatric room throughout session. One (the practitioner) ought to take care to make use of finest observe 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 would do us an entire 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 remedy on account of unwanted side effects from the remedy.
Edited by
Edited by Simon Bradstreet.
Hyperlinks
Main 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 Vital Decline of Glomerular Filtration Price within the Majority of Lengthy-Time period Lithium Customers: Outcomes of a Dutch Potential 10-12 months Cohort Examine. Bipolar Problems, 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 Price in Sufferers With Affective Problems: A Inhabitants-Based mostly Cohort Examine, Lancet Psychiatry 2, no. 12: 1075–1083
