Psychotropic Drugs and Adverse Kidney Effects: A Systematic Review of the Past Decade of Research.

BACKGROUND AND OBJECTIVE: Psychotropic drugs are a heterogenous group of treatments prescribed for many psychiatric disorders, often for long periods. Their effects on the kidney and its functioning are complex and a source of significant research and debate. This article aims to review recent evidence of the acute and chronic kidney adverse events of diverse psychotropes. METHODS: A systematic search of randomized controlled trials and large observational studies (n ≥ 100) reporting the effects of psychotropic drugs on the kidney was conducted. The MEDLINE, PsycInfo, and EMBASE databases from 2011 to 2021, inclusive, were broadly searched with few restrictions and no prespecified outcomes. Two or more independent reviewers assessed and summarized all eligible studies, including risks of bias and levels of evidence. RESULTS: In all, 1999 abstracts were screened for eligibility and 47 articles were included, which examined lithium (33), antiepileptics (10), antipsychotics (13), and antidepressants (9). No studies examining kidney adverse effects of other psychotropes, such as benzodiazepines, met inclusion criteria. Study populations were adult (8), geriatric (9), and mixed (30). Lithium was almost unanimously associated with (1) chronic kidney disease and (2) nephrogenic diabetes insipidus in methodologically diverse studies. The most supported risk factors for declining kidney functioning with lithium were advanced age, duration of lithium treatment, acute lithium toxicity, female sex, medications with known renal interactions, diabetes mellitus/hyperglycemia, and overall medical comorbidity. Supratherapeutic lithium concentrations are both the causes and consequences of acute kidney injury. Once significant chronic kidney disease has developed, four studies found that replacing lithium with other mood stabilizers does not slow progression, and the evolution to end-stage kidney disease is rare overall with modern practices. Compared to lithium, fewer studies examined antipsychotics and antiepileptics but found relatively less direct kidney harms. Antidepressants were not associated with acute or chronic kidney harms. CONCLUSIONS: Despite the heterogeneity of findings, owing to varying methodologies and research challenges, recent studies strongly suggest that lithium is associated with an increased risk of chronic kidney disease and nephrogenic diabetes insipidus, especially in older adults and long-term lithium users. Clinicians should balance the harms of lithium against its established benefits, and ensure adequate monitoring and management of comorbidities in all patients. Weaker evidence suggests that antiepileptics such as valproate and antipsychotics result in comparatively less harm to the kidney than lithium, but warrant monitoring because of multiple direct and indirect mechanisms for potential kidney adverse events. Antidepressants do not have clear kidney adverse effects and appear safe (though potentially less effective) in the setting of kidney disease. Other classes of psychotropic drugs have received little research interest. Further research is warranted, particularly into specific antiepileptics and antipsychotics, and careful attention should be paid to mitigating important sources of bias such as confounding by indication.

Corticosteroids Use and Incidence of Severe Infections in People Living with HIV Compared to a Matched Population.

BACKGROUND: People living with HIV (PLWH) have been shown to have an increased risk of autoimmune diseases. Corticosteroids are the cornerstone of autoimmune diseases treatment, but their use is associated with an increased risk of infections. It is unclear how HIV status affects the risk of infection associated with corticosteroids use. METHODS: We conducted a retrospective cohort study from 1991 to 2011, using a medico-administrative database from Quebec. Medical billing codes were used to identify PLWH, and we matched them on age, sex, and index date with up to 4 HIV-negative controls. The exposure of interest was the use of corticosteroids, defined as a systemic corticosteroid dispensation lasting at least 20 days. The outcome of interest was hospitalization for severe infection. Crude and adjusted incidence rates ratios of infection were obtained using a random effect Poisson model, and results were stratified by HIV status. RESULTS: In total, 4798 PLWH were matched to 17 644 HIV-negative controls, among which 1083 (22.6%) PLWH and 1854 (10.5%) HIV-negative controls received at least one course of corticosteroid. The mean duration of corticosteroids use was 4 ± 4.4 months in PLWH and 1.6 ± 5.5 months in HIV-negative controls. The incidence rate ratio (IRR) for infections associated with corticosteroids use was 2.49[1.71-3.60] in PLWH and 1.32[0.71-2.47] in HIV-negative controls (P value for interaction 0.18). The most frequent infections were pulmonary infections (50.4%), followed by urinary tract infections (26%) and opportunistic infections (10.5%). CONCLUSION: Although our interaction term did not reach significance, the increased risk of infection associated with corticosteroids use was more pronounced in PLWH. However, further research with contemporary data is warranted to confirm if the risk associated with corticosteroids use remains high in PLWH with well-controlled HIV infection.

Incidence of autoimmune diseases in people living with HIV compared to a matched population: a cohort study.

The objective of this paper is to estimate incidence and relative risk of autoimmune conditions in patients living with HIV compared to an HIV-negative matched population. We conducted a retrospective study in the medico-administrative database of the province of Québec, Canada. All HIV-positive patients treated with antiretrovirals were matched to up to 4 HIV-negative controls for age, sex, and period of follow-up. The following autoimmune conditions were identified using medical billing codes: vasculitis, hematological (immune thrombocytopenic purpura and immune hemolytic anemia), ankylosing spondylitis, psoriasis and psoriatic arthritis, inflammatory bowel disease and associated arthritis, connectivitis, and systemic lupus erythematosus. Incidence rates and adjusted hazard ratios (aHR) were obtained using survival models. A total of 4245 HIV-positive patients were matched to 16493 HIV-negative patients. Autoimmune diseases were diagnosed in 407 (9.6%) HIV-positive and 508 (3%) HIV-negative patients. The aHR for autoimmune diseases associated to HIV was 2.40 95% CI [2.10-2.75]. The strongest associations were seen for hematological disorders (aHR 8.34 95% CI [6.13-11.36]), followed by ankylosing spondylitis (1.82 95% CI [1.03-3.21]), inflammatory bowel disease and associated arthritis (1.80 95% CI [1.37-2.35]), psoriasis and associated arthritis (1.69 95% CI [1.23-2.33]), and rheumatoid arthritis (1.51 95% CI [1.08-2.11]).We found no association between HIV and the incidence of vasculitis, connectivitis, and systemic lupus erythematosus, but the number of cases for these diseases were few. Autoimmune diseases are more frequent among people living with HIV than age and sex-matched population-based controls. Key Points • Strength: The major strength of this study is its large sample size of 4200 people treated as HIV infection, matched to 16000 HIV negative for sex and age. • Novelty: We found that people living with HIV were more than twice as likely to suffer from auto-immune diseases than their matched counterparts.