Stratifying Risk for Renal Insufficiency Among Lithium-Treated Patients: An Electronic Health Record Study (original) (raw)
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The impact of long-term lithium treatment on renal function in an outpatient population
The Ulster medical journal, 2008
This study aims to compare younger and older populations of lithium-treated patients and to examine the impact of long-term lithium treatment on renal function. A retrospective, cross-sectional survey of all patients attending a specialist clinic was carried out. Demographic, clinical and biochemical data from the two groups were compared, and stepwise regression was used to investigate an association between duration of lithium treatment and renal function. The findings reveal a positive association between duration of lithium use and mean serum creatinine levels (t=3.369, p=0.001), and so prolonged lithium treatment may be a risk factor for progressive renal impairment. However, under appropriate supervision this may not be of clinical relevance. We conclude that lithium can be safely prescribed over a protracted period of time, even in elderly populations, but should be monitored closely under specialist supervision, to ensure early identification and management of adverse effects.
Lithium nephrotoxicity: when and why? Experience of nephrology and psychiatry outpatient clinics
Nephrology and renal diseases, 2021
Background: Lithium salts are widely used in the treatment of bipolar disorders. Lithium-induced nephropathy is a complication occurring after several years of lithium exposure and accounts for 0.2% of the dialysis population. Whether other pre-existing renal pathologies may potentiate or accelerate this progression of lithium nephropathy is a controversial matter. Therefore, the aim of this case-controlled study was to analyse and identify the factors which may influence long-term renal outcome. Methods: The clinical and laboratory data of 7 patients of the nephrology unit who were under long-term lithium therapy and had moderately to severely impaired renal function (G3a-G5), were compared to that of 7 psychiatry clinic patients under the same treatment whose renal function was normal or mildly compromised (G1-2). The lithium nephropathy diagnosis was based on the presence of long-term lithium treatment, renal impairment and/or the presence of renal cysts. The population characteristics, including comorbidities, duration of lithium treatment and its dosage and episodes of toxicity were taken into account. Results: The patients in the G3a-G5 group had more pre-existing renal conditions and had a higher incidence of severe nephropathy despite being treated for a shorter amount of time and with lower lithium doses compared to the patients in the G1-2 group. Moreover, they presented additional risk factors such as lithium intoxication and nephrogenic diabetes insipidus. Conclusion: Careful assessment of pre-existing renal disease should be performed before initiation of lithium therapy, especially in elderly co-morbid patients with multiple risk factors. Close monitoring and patients' education are mandatory for patients who undergo long-term lithium treatment.
Renal function during long-term lithium treatment: a cross-sectional and longitudinal study
BMC Medicine, 2015
Background: The effects of lithium treatment on renal function have been previously shown, albeit with discrepancies regarding their relevance. In this study, we examined glomerular filtration rate in patients treated with lithium for up to 33 years. Methods: All lithium patients registered from 1980 to 2012 at a Lithium Clinic were screened. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine concentration using the Modification of Diet in Renal Disease Study Group equation. A cross-sectional evaluation of the last available eGFR of 953 patients was carried out using multivariate regression analysis for gender, current age, and duration of lithium treatment. Survival analysis was subsequently applied to calculate the time on lithium needed to enter the eGFR ranges 45 to 59 mL/min/1.73 m 2 (G3a) or 30 to 44 mL/min/1.73 m 2 (G3b). Finally, 4-year follow-up of eGFR was examined in subgroups of patients who, after reduction to an eGFR lower than 45 mL/min/1.73 m 2 either i) continued lithium at the same therapeutic range or ii) discontinued lithium or continued at concentrations below the therapeutic range (0.5 mmol/L). Results: In the cross-sectional evaluation, eGFR was found to be lower in women (by 3.47 mL/min/1.73 m 2), in older patients (0.73 mL/min/1.73 m 2 per year of age), and in patients with longer lithium treatment (0.73 mL/min/1.73 m 2 per year). Half of the patients treated for longer than 20 years had an eGFR lower than 60 mL/min/1.73 m 2. The median time on lithium taken to enter G3a or G3b was 25 years (95% CI, 23.2-26.9) and 31 years (95% CI, 26.6-35.4), respectively. Progression of renal failure throughout the 4-year follow-up after a reduction to an eGFR lower than 45 mL/min/1.73 m 2 did not differ between the subgroup who continued lithium as before and the subgroup who either discontinued lithium or continued at concentrations below the therapeutic range. Conclusions: Duration of lithium treatment is to be added to advancing age as a risk factor for reduced glomerular filtration rate. However, renal dysfunction tends to appear after decades of treatment and to progress slowly and irrespective of lithium continuation.
BMC Medicine, 2013
Background: The adverse renal effects of lithium have long been known, but glomerular insufficiency had been considered an unlikely event until recently, when new studies have raised concern regarding very long-term treatment. In this cross-sectional study, we examined glomerular function in a cohort of patients treated with lithium for up to 33 years and a control group of lithium-naïve patients treated with other mood-stabilizers. Methods: Patients with a diagnosis of recurrent or persistent affective disorders, examined between 1 October 2007 and 31 December 2009, were screened. Demographic and clinical data were extracted from clinical charts regarding two study groups: one for patients treated with lithium for at least 12 months and the other for patients never exposed to lithium. Multivariate regression analysis was applied: the dependent variable was the estimated glomerular filtration rate (eGFR) calculated from the last available serum creatinine value using the Modification of Diet in Renal Disease Study Group equation; the following independent variables, potentially associated with renal dysfunction, were included: gender, current age, duration of lithium treatment, cigarette smoking, hypertension, diabetes and dyslipidemia. Results: eGFRs lower than 60 ml/min were significantly more frequent in the group treated with lithium (38/139 = 27.3%) compared to lithium-naïve patients (4/70 = 5.7%) (P = 0.0002; Fisher's test). Regression analysis showed a significant effect on eGFR of age, gender and duration of lithium treatment but no effect of cigarette smoking, hypertension, diabetes or dyslipidemia. eGFR was estimated to decrease by 0.64 ml/min (95% confidence interval = 0.38 to 0.90; P = 0.00) for each year of lithium treatment. Conclusions: The duration of lithium treatment is a risk factor for glomerular failure, in addition to advancing age. For example, all patients aged 60 years or older may be estimated to undergo Stage 3 or more severe chronic kidney disease (namely an eGFR less than 60 ml/min) if treated with lithium for 30 years. These data may be added to the current debate on the balance between the protective effects of lithium on recurrent affective disorders and suicide and the risk of renal disease. See related commentary article here
Relationship between serum lithium concentration and kidney damage in a preclinical model
Bipolar Disorders, 2019
Despite several decades of use, lithium remained the "gold standard" in the long-term prophylactic treatment of bipolar disorder (BD). 1 One disturbing adverse effect associated with the prolonged use of lithium is the development of chronic kidney disease (CKD), which may be less infrequent than was commonly thought. In fact, stage 3 of CKD (defined as a decrease in the estimated glomerular filtration rate-eGFR-below 60 mL/min/1.73 m 2) could be observed in up to 20%-40% of patients under long-term treatment with lithium, a percentage that could be higher even among older adults. 2-4 Although the development of CKD does not always imply serious clinical concerns, between 1% and 2% of patients could progress to an end stage renal disease (or CKD stage 5) requiring dialysis or kidney transplantation. 5,6 In this context, knowledge of the risk factors for the development of CKD associated with long-term lithium treatment is challenging, and could contribute to a more rational use of this therapeutic agent. There is some convergent evidence that the risk of developing CKD could be associated with the duration of treatment (often more than a decade), old age, prior episodes of lithium toxicity, medical comorbidities (ie, diabetes or hypertension), and the concomitant use of other medications with nephrotoxic potential (such as angiotensin converting enzyme inhibitors or non-steroidal anti-inflammatory agents). 7 On the contrary, the risk associated with serum lithium concentrations-when they are within the therapeutic
Response to the comments on ‘Continuation of lithium after a diagnosis of chronic kidney disease’
Acta Psychiatrica Scandinavica, 2018
We consider that the information provided by Kessing et al. (1) in their recent paper of this title fails to justify their conclusion. This causes us considerable concern, as we fear that it could encourage inappropriate and potentially dangerous treatments with lithium. The weaknesses in their study appear to derive from several factors. They claim that only 238 of 754 Danish patients treated with lithium suffered from bipolar disorder, but fail to identify the reason for lithium treatment in the remaining large majority. From what diseases did these other people suffer to justify treatment with this powerful drug? They furthermore provide no evidence regarding the duration of exposure of any of the patients, bipolar or otherwise, to lithium. Favourable outcomes in patients who only had brief exposure may well obscure unfavourable outcomes in others with protracted exposure. End-stage renal failure can cause patients such devastating torture that even one unnecessary case is one too many. The median lengths of follow-up of the patients whom they surveyed were less than six years, whereas evidence exists to suggest that the typically slow course of lithium nephrotoxicity makes follow-up of more than ten years necessary for meaningful assessment (2-4). The fact that the authors did not have access to detailed data on renal function has then exacerbated their difficulty in achieving a persuasive interpretation. But the authors go further. They state that 'In the larger cohorts of all patients with a first diagnosis of CKD and a history of either lithium or anticonvulsants, rates of end-stage CKD were decreased among individuals continuing versus discontinuing the mood stabiliser'. If their analysis is valid, then the logical conclusion surely is that all patientspsychiatric or notwho demonstrate any degree of renal impairment should commence lithium treatment to protect their kidneys. Such a proposal appears so outlandish as to question the validity of their analysis. Indeed why, if they are correct in suggesting that lithium treatment is so beneficial for renal function, do they then suggest that 'careful monitoring of kidney function' in patients exposed to ongoing lithium treatment is necessary? Lithium treatment surely would have rendered such monitoring redundant. We are not convinced that modern Lithium treatment within recommended blood levels has eliminated Lithium nephrotoxicity. Information that we have published (5) has led to conclusions diametrically opposite to those reached by Kessing et al. Their study does not encourage us to revise our opinions. We suggest that clinicians should replace lithium with an alternative mood stabiliser in patients who demonstrate a decrease in renal function on two consecutive and confirmed tests of serum creatinine concentration, or who have a glomerular filtration rate of <45 mL/min/1.75 m 2