Lithium continues to be a primary line remedy for temper situations comparable to bipolar dysfunction, and rightfully so, because it continues to be unmatched in its capability to stabilise moods (see, for instance, this current weblog about diminished hospitalisations being related to Lithium use).
Nevertheless, its adverse impression on kidneys is nicely documented and, should you belong to any severe 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 dwell with a severe psychological sickness. We’re not the hen whose contribution to breakfast is an egg; we’re the pig whose contribution to breakfast is a sausage. We’ve severe 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 standards for inclusion have been:
- sufferers dwelling with a temper dysfunction,
- have been prescribed lithium,
- have been lively within the medical system, and
- had a follow-up of greater than a 12 months.
They ended up having 196 sufferers of which 42% have been male, with a imply age of 51.1 years at begin. The measurements for use have been based mostly on estimated glomerular filtration charge (eGFR: a key indicator of how nicely 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 some other drugs (comedication), and
- whether or not any sufferers stopped lithium through the ten 12 months interval.
Sufferers who stopped lithium through the research have been monitored for any additional decline in eGFR.
The researchers had their work reduce out for them. Sufferers who stopped utilizing lithium have been in contrast towards these sufferers who continued lithium remedy. And, sufferers who stopped lithium remedy as a result of eGFR decline have been in contrast towards sufferers who ceased lithium remedy for different causes. Medicines recognized to affect eGFR decline besides lithium have been fastidiously excluded. The analysis staff 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 have been linear nonetheless eGFR trajectories weren’t linear in sufferers who have been both pregnant or admitted in scientific hospitals. And so sufferers’ outcomes whereas hospitalised and when pregnant have been excluded. The median decline in eGFR in sufferers was 0.79 mL/min/1.73 m2 per 12 months; 11% of the individuals 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 big affiliation between median length (which was 16 years) and eGFR discount. Different drugs recognized to extend the chance of kidney decline weren’t discovered to have a big affiliation with eGFR decline when the outcomes have been corrected for intercourse and age.
Thirty 9 of the 196 sufferers stopped lithium remedy. In 18 situations the explanations for discontinuation have been as a result of documented unintended effects together with kidney decline, nephrotoxicity (kidney injury), 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 basic Netherlands inhabitants, suggesting that the elevated decline was linked to the long run use of lithium. The analysis staff additionally famous that earlier than ceasing lithium, the sufferers who stopped utilizing lithium skilled comparable decline in eGFR to those that stayed on lithium through the tenure of the research. Of the 39 sufferers who stopped lithium, solely 33 had observe up data 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 important for the needs of this research when tracked throughout this ten 12 months interval. One other potential purpose for them concluding that there was no important slowing in kidney decline is that that they had a small variety of individuals of their research after which an excellent smaller variety of individuals stopping lithium. It is also potential that they didn’t see statistically important enchancment as a result of they might not monitor the long run variations.
Furthermore the analysis staff discovered that there was a big relationship between larger serum concentrations and eGFR decline, which means there may be an affiliation between lithium remedy and kidney operate decline. The staff discovered no proof that comedication between lithium and nephrotoxic drugs could possibly 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 individuals had sooner eGFR decline than the imply decline within the basic inhabitants. Lithium publicity, quantified as imply serum lithium focus, could possibly be a contributing issue on this decline.
Strengths and limitations
I agree with the analysis staff that their research was essential as a result of that they had lengthy observe up time and their cohort had been on lithium for a protracted interval, they might use the outcomes from bi-annual monitoring of sufferers who’re on lithium to assemble a trajectory of their kidneys.
The research additionally had various limitations beginning with the truth that, as an observational research, it’s not potential 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 essential. 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 experiences 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 think there may have been simply because consultations are so brief that there isn’t any time to relay every part to the physician. So you permit with the identical prescription for drugs that fill your medication cupboard, taken on an “as and after I see mandatory foundation”.
Different research have hypothesised that the presence of comorbidities (hypertension, diabetes and so forth) could possibly be a potential purpose for the eGFR decline (Clos et al, 2015), nonetheless 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 could possibly be the precise reason behind the eGFR decline. The analysis staff recognises that one of many research limitations, like different research investigating lithium’s impression on the kidneys, was it didn’t have a big sufficient cohort. This makes it more durable to have faith in its findings, which is regarding given the seriousness of those unintended effects and the significance of lithium as a remedy.
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 impression of lithium use on the kidneys. It additionally adopted the sufferers as an alternative of gathering information 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 diminished is useful. And what of the temper instability that might happen because of stopping lithium remedy?
Though in all probability 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 realize temper stability and basic optimum scientific outcomes. van der Aa et al. help the monitoring of lithium concentrations as per the present tips and measuring kidney operate in a fashion that’s individualised. Importantly, they make no suggestion on the plan of action to be taken when people who find themselves taking lithium start experiencing kidney decline.
The analysis staff 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 can be used to verify whether or not there’s a level of no return in the case of kidney decline.
Now keep in mind, there are often two individuals within the psychiatric room throughout session. One (the practitioner) ought to take care to make use of greatest apply when prescribing the dose of lithium to be taken by the affected person. The opposite (the affected person) ought to keep in mind that they’re the proverbial pig and never the hen, so it’s going to do us an entire lot of fine to be our personal greatest 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 as a result of unintended 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 Fee within the Majority of Lengthy-Time period Lithium Customers: Outcomes of a Dutch Potential 10-Yr 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 Fee in Sufferers With Affective Issues: A Inhabitants-Based mostly Cohort Research, Lancet Psychiatry 2, no. 12: 1075–1083
Discussion about this post