AJKD Atlas of Renal Pathology: Lithium Nephrotoxicity

Fogo, Agnes B.; Lusco, Mark A.; Andeen, Nicole K.; Najafian, Behzad; Alpers, Charles E.

doi:10.1053/j.ajkd.2016.11.005

Cited by 8 publications

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“…A recently published population based study that have found that after adjusting for age, sex, and baseline estimated glomerular filtration rate (eGFR) there was no significant difference in the rate of decline between subjects on lithium and controls, and perhaps the observed differences in prior papers has been a result of methodological flaws [ 8 ]. Despite these variable findings within the literature, the predominant view is one of lithium having the ability to cause a chronic tubulointerstitial nephritis which leads to progressive CKD over a period of many years and ESKD in about 1.5% of long term lithium users [ 9 ]. Delineating the risk factors for the development of CKD, as well as providing clinicians with a guide as to the optimal management of patients on lithium with progressive CKD is challenging.…”

Section: Introductionmentioning

confidence: 99%

Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification

2018

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BackgroundDespite lithium being the most efficacious treatment for bipolar disorder, its use has been decreasing at least in part due to concerns about its potential to cause significant nephrotoxicity. Whilst the ability of lithium to cause nephrogenic diabetes insipidus is well established, its ability to cause chronic kidney disease is a much more vexing issue, with various studies suggesting both positive and negative causality. Despite these differences, the weight of evidence suggests that lithium has the potential to cause end stage kidney disease, albeit over a prolonged period.MethodsA search strategy for this review was developed to identify appropriate studies, sourced from the electronic databases EMBASE, PubMed (NLM) and MEDLINE. Search terms included lithium with the AND operator to combine with nephrotoxicity or nephropathy or chronic kidney disease or nephrogenic diabetes insipidus or renal and pathophysiology.ResultsThe risks for the development of lithium induced nephropathy are less well defined but appear to include the length of duration of therapy as well as increasing age, as well as episodes of over dosage/elevated lithium levels. Whilst guidelines exist for the routine monitoring of lithium levels and renal function, it remains unclear when nephrological evaluation should occur, as well as when cessation of lithium therapy is appropriate balancing the significant attendant mental health risks as well as the potential for progression to occur despite cessation of therapy against the risks and morbidity of bipolar disorder itself.ConclusionThis paper will elucidate on the current evidence pertaining to the topic of the clinical management of lithium induced nephrotoxicity and provide a guide for clinicians who are faced with the long-term management of these patients.

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Section: Introductionmentioning

confidence: 99%

Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification

2018

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“…Complicating issues, other agents used in mood disorders such as antipsychotics may also be associated with renal dysfunction, although the data is far more tentative . There are no specific findings on immunofluorescence staining, whilst electron microscopy may show variable foot process effacement within the glomeruli . Lithium may also have the potential to be directly toxic to podocytes.…”

Section: Lithium Induced Nephropathy: Biopsy Findingsmentioning

confidence: 99%

Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal

2018

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This paper elucidated the current evidence pertaining to the pathophysiology of lithium induced nephrotoxicity and nephrogenic diabetes insipidus. The molecular mechanisms behind are the development of alterations in glycogen synthase kinase 3 signalling, G2 cell cycle progression arrest, alterations in inositol and prostaglandin signalling pathways, and dysregulated trafficking and transcription of aquaporin 2 water channels. ABSTRACT:While lithium remains the most efficacious treatment for bipolar disorder, it can cause significant nephrotoxicity. The molecular mechanisms behind both this process and the development of nephrogenic diabetes insipidus still remain to be fully elucidated but appear to involve alterations in glycogen synthase kinase 3 signalling, G2 cell cycle progression arrest, alterations in inositol and prostaglandin signalling pathways, and dysregulated trafficking and transcription of aquaporin 2 water channels. The end result of this is a tubulointerstitial nephropathy with microcyst formation and relative glomerular sparing, both visible on pathology specimens and increasingly noted on non-invasive imaging. This paper will elucidate the current evidence pertaining to the pathophysiology of lithium induced nephrotoxicity.

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“…Beside lithium-induced NDI, its ability to cause chronic kidney disease (CKD) is a much more debated issue in the literature, with various studies suggesting both a positive and negative relationship (Azab et al 2015 ; Clos et al 2015 ; Gitlin 2016 ) (Gupta and Khastgir 2017 ). Despite these conflicting data, the predominant view seems to be that lithium has the capacity to cause chronic tubulointerstitial nephritis leading to progressive CKD over several years and end stage renal disease (ESRD) in about 1.5% of long-term lithium users (Fogo et al 2017 ). To go further, the definition of risk factors for the development of CKD on lithium remains to date very poorly documented.…”

Section: Introductionmentioning

confidence: 99%

Long-term lithium therapy and risk of chronic kidney disease, hyperparathyroidism and hypercalcemia: a cohort study

Boivin

Daré

Bellay

et al. 2023

Int J Bipolar Disord

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Background Lithium is well recognized as the first-line maintenance treatment for bipolar disorder (BD). However, besides therapeutic benefits attributed to lithium therapy, the associated side effects including endocrinological and renal disorders constitute important parameters in prescribing patterns and patient adherence. The objectives of this study is to (i) determine whether long-term lithium therapy is associated with a decrease in renal function, hyperparathyroidism and hypercalcemia and (ii) identify risk factors for lithium-induced chronic kidney disease (CKD). Methods We conducted a single-centered cohort study of adult patients (≥ 18 years) treated with lithium, who were enrolled at Rennes University Hospital in France between January 1, 2018 and June 1, 2020. Required data were collected from the patient’s medical records: demographics characteristics (age, sex, body mass index), biologic parameters (GFR, lithium blood level, PTH and calcium), medical comorbidities (hypertension and diabetes), lithium treatment duration and dosage, and length of hospitalization. Results A total of 248 patients were included (mean age: 60.2 ± 16.5 years). Duration of lithium treatment correlated with (i) deterioration of renal function estimated at − 2.9 mL/min/year (p < 0.0001) and (ii) the development of hyperparathyroidism (p < 0.01) and hypercalcemia (p < 0.01). We also noted that patients with lithium blood level > 0.8 mEq/mL had significantly lower GFR than patients with lithium blood level < 0.8 mEq/mL (61.8 mL/min versus 77.6 mL/min, respectively, p = 0.0134). Neither diabetes mellitus nor hypertension was associated with more rapid deterioration of renal function. Conclusion This study suggests that the duration of lithium treatment contribute to the deterioration of renal function, raising the question of reducing dosages in patients with a GFR < 60 mL/min. Overdoses has been identified as a risk factor for CKD, emphasizing the importance of regular re-evaluation of the lithium dose regimen. Also, long-term lithium therapy was associated with hyperparathyroidism and hypercalcemia. Particular vigilance is required on these points in order to limit the occurrence of endocrinological and renal lithium adverse effects.

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AJKD Atlas of Renal Pathology: Lithium Nephrotoxicity

Cited by 8 publications

References 0 publications

Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification

Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification

Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal

Long-term lithium therapy and risk of chronic kidney disease, hyperparathyroidism and hypercalcemia: a cohort study

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