Lithium side effects and toxicity: prevalence and management strategies

Despite its virtually universal acceptance as the gold standard in treating bipolar disorder, prescription rates for lithium have been decreasing recently. Although this observation is multifactorial, one obvious potential contributor is the side effect and toxicity burden associated with lithium. Additionally, side effect concerns assuredly play some role in lithium nonadherence. This paper summarizes the knowledge base on side effects and toxicity and suggests optimal management of these problems. Thirst and excessive urination, nausea and diarrhea and tremor are rather common side effects that are typically no more than annoying even though they are rather prevalent. A simple set of management strategies that involve the timing of the lithium dose, minimizing lithium levels within the therapeutic range and, in some situations, the prescription of side effect antidotes will minimize the side effect burden for patients. In contrast, weight gain and cognitive impairment from lithium tend to be more distressing to patients, more difficult to manage and more likely to be associated with lithium nonadherence. Lithium has adverse effects on the kidneys, thyroid gland and parathyroid glands, necessitating monitoring of these organ functions through periodic blood tests. In most cases, lithium-associated renal effects are relatively mild. A small but measurable percentage of lithium-treated patients will show progressive renal impairment. Infrequently, lithium will need to be discontinued because of the progressive renal insufficiency. Lithium-induced hypothyroidism is relatively common but easily diagnosed and treated. Hyperparathyroidism from lithium is a relatively more recently recognized phenomenon

[Progressive renal failure caused by lithium nephropathy]

OBJECTIVES: Study the renal consequences of lithium therapy and find out whether lithium-induced chronic renal toxicity can provoke a progressive nephropathy, leading to advanced renal failure, requiring periodical dialysis. METHODS: Fifty-three patients treated with long-term lithium salts were included in the study. They had developed chronic renal failure (creatinine clearance inferior to 80 ml/min) not due to any other cause. RESULTS: These patients had received lithium salts for a mean period of 17.7 years. The mean reduction in creatinine clearance was of 2.23 ml/min/year. Final clearance correlated negatively with the duration of lithium administration. In 7 patients treated a mean of 22 years, progression towards terminal kidney failure required periodical dialysis. Around 30% of patients exhibited mild hypercalcemia. CONCLUSION: Lithium nephropathy inducing progressive renal failure is a reality. Its prevalence in patients treated long-term with lithium should be assessed

Lithium-induced nephropathy: Rate of progression and prognostic factors

BACKGROUND: Long-term lithium administration in humans may lead to chronic tubulointerstitial nephritis, which develops very slowly. Its progression to end-stage renal disease (ESRD) has been rarely reported. The aim of this study is to document the rate of progression of lithium-induced nephropathy and its prognostic factors, and to provide an estimation of the percentage of lithium-induced ESRD in France. METHODS: Two groups have been studied: 54 patients with lithium-induced renal failure, nine of whom underwent renal biopsy; and 20 patients who were referred for systematic renal biopsy, 14 of whom were subsequently followed up. In addition, a survey of lithium-induced ESRD was conducted in French dialysis centers. RESULTS: The mean annual loss of creatinine clearance in patients with lithium-induced nephropathy was 2.29 mL/min. Among 74 patients, 12 reached ESRD at a mean age of 65 years. Creatinine clearance at referral and at last follow-up was inversely related to the duration of lithium therapy in both univariate and multivariate analyses adjusting for age, gender, hypertension, and proteinuria. The degree of interstitial fibrosis on renal biopsy was also related to the lithium duration and cumulative dose. It was predictive of the final creatinine clearance. About 35% of the patients tested had moderate hypercalcemia, due to hyperparathyroidism. The prevalence of lithium-related ESRD in France was estimated as two per 1000 dialysis patients. The average latency between onset of lithium therapy and ESRD was 20 years. CONCLUSION: Lithium-induced chronic renal disease is slowly progressive. Its rate of progression is related to the duration of lithium administration. Lithium-related ESRD represents 0.22% of all causes of ESRD in France. Regular monitoring of estimated creatinine clearance is mandatory in long-term lithium-treated patients

Anticorps anti-annexines et calcifications artérielles au cours du lupus érythémateux systémique : étude transversale

International audienceLa maladie cardiovasculaire due à une athérosclérose précoce et accélérée représente une cause majeure de morbi-mortalité au cours du lupus érythémateux systémique (LES). Une augmentation significative de la prévalence des calcifications artérielles au cours du LES a été rapportée. Les calcifications cardiovasculaires sont reconnues comme étant associées à un risque cardiovasculaire élevé. Les facteurs de risque cardiovasculaire traditionnels n’expliquent pas totalement la majoration du risque cardiovasculaire au cours du LES. D’autres facteurs inhérents au LES sont impliqués tels que l’activité de la maladie, certains traitements ou encore l’auto-immunité. Il a été montré que l’annexine A2 et l’annexine A5 pouvaient avoir des effets athéroprotecteurs. L’objectif de notre étude est de rechercher une association entre les anticorps anti-annexines et les calcifications artérielles chez des patientes lupiques. Les patientes présentant un LES répondant aux critères de classification du lupus de l’American College of Rheumatology (1997) et suivies dans 2 centres hospitaliers universitaires français ont participé à cette étude, après information et recueil de leur consentement écrit. Des données démographiques et cliniques ont été colligées telles que l’âge et les facteurs de risque cardiovasculaire traditionnels (HTA, dyslipidémie, tabagisme actif, diabète, obésité). Les patientes lupiques ont bénéficié de différents examens radiologiques afin de rechercher la présence de calcifications cardiovasculaires : échographie cardiaque, scanner coronarien et aortique, échographie doppler des troncs supra-aortiques, de l’aorte abdominale et des artères des membres inférieurs. Nous avons recherché différents auto-anticorps d’isotype IgG et IgM : anticardiolipine (ACL), anticorps anti-b2 glycoprotéine I (aB2GPI), anticorps anti-annexine A2 (aANXA2) et anticorps anti-annexine A5 (aANXA5). Nous avons inclus 69 patientes d’avril 2011 à mai 2015. L’âge médian à l’inclusion était de 43,3 [22–74] ans. La prévalence des facteurs de risque cardiovasculaire « classiques » était : HTA (21,4 %), tabagisme actif (23,5 %), dyslipidémie (14,4 %), diabète (1,4 %), obésité (27,9 %). Nous avons observé au moins une calcification vasculaire chez 47,8 % des patientes. La prévalence des différentes calcifications cardiovasculaires selon leur localisation était : calcifications coronariennes (26 %), calcifications de l’aorte thoracique (33,3 %), calcifications de l’aorte abdominale (26 %), calcifications valvulaires (14,4 %), calcifications des artères des membres inférieurs (7,2 %), calcifications des troncs supra-aortiques (7,3 %). La positivité des anticorps antiphospholipides « conventionnels » (ACL et/ou aB2GPI) était observée chez 22,3 % des patientes. La présence des aANXA2 et des aANXA5 était observée respectivement chez 10,4 % et 6 % des patientes. Aucune association n’a été retrouvée entre la positivité des aANXA5 et la présence de calcifications artérielles. Cependant, nous avons observé une association entre la présence d’aANXA2 et les calcifications coronariennes (p = 0,0095). Nous avons observé une prévalence élevée des calcifications cardiovasculaires au cours du LES. L’association observée entre la présence d’anticorps dirigés contre l’annexine A2 et les calcifications coronariennes laisse supposer que ces anticorps pourraient avoir un rôle pro-athérogène. D’autres études seront nécessaires afin de confirmer ces données

Steroid-sensitive nephrotic syndrome: from childhood to adulthood

BACKGROUND: The clinical presentation, treatment, and outcome of steroid-sensitive nephrotic syndrome (SSNS) during childhood have been extensively studied. Conversely, few data regarding the outcome in adulthood of childhood SSNS have been published previously. We undertook to conduct a retrospective study of the outcome in adulthood of a large cohort of patients diagnosed with an SSNS during childhood. METHODS: We identified all children born between 1970 and 1975 who had been admitted to our institution for an SSNS. Data regarding the outcome in adulthood of these patients were obtained through mailed questionnaires or phone calls to patients and/or their parents or through attending physicians. RESULTS: One hundred seventeen patients were identified. Data regarding the outcome of SSNS in adulthood were available for 102 patients (87.2%). Forty-three patients (42.2%) experienced at least one relapse of nephrotic syndrome in adulthood. By univariate analysis, young age at onset (<6 years) and more severe disease in childhood, indicated by a greater number of relapses (12.9 for adulthood relapsers versus 5.4 for adulthood nonrelapsers; P < 0.0001) and more frequent use of immunosuppressors (74.4% versus 31.6%; P < 0.0001) or cyclosporine (42.9% versus 7.3%; P < 0.0001) were predictive of the occurrence of SSNS relapse in adulthood. Conversely, relapse rate in the first 6 months of disease was not predictive of further relapses in adulthood. By multivariate analysis, only number of relapses during childhood was predictive of adulthood relapses (P < 0.0058). Long-term side effects of steroids were found in 44.2% of adulthood relapsers; the most frequent were osteoporosis and excess weight. CONCLUSION: The incidence of childhood SSNS relapses in adulthood was relatively high in our study. Further studies are required to assess long-term complications in adults with relapses and a history of prolonged steroid and immunosuppressor use