Drug information update. Lithium and chronic kidney disease: debates and dilemmas.
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ABSTRACT:
SUBMITTER: Gupta S
PROVIDER: S-EPMC5537577 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:Purpose of reviewDirect oral anticoagulants (DOACs) are variably eliminated by the kidneys rendering their use potentially problematic in patients with chronic kidney disease (CKD) or necessitating appropriate dose adjustment.Recent findingsBoth observational and limited randomized trial data for DOACs compared with no treatment or with warfarin for patients with atrial fibrillation on maintenance dialysis were recently published. In a randomized trial in patients on hemodialysis, there was no significant difference in vascular calcification between patients who received rivaroxaban with or without vitamin K2 or vitamin K antagonists. A randomized trial of apixaban versus warfarin was terminated owing to poor enrollment and preliminary results identified no difference in clinical outcomes between groups. However, valuable pharmacodynamic data will be forthcoming from that trial. In observational research, among patients newly diagnosed with atrial fibrillation, there were opposing trends in the associations of apixaban initiation versus no oral anticoagulation with ischemic versus hemorrhagic stroke and no association was present with the overall risk of stroke or embolism. In another study comparing apixaban with warfarin initiation, apixaban was associated with less bleeding. Regular-dose apixaban (5 mg twice daily) associated with reduced rates of ischemic stroke or systemic embolism, whereas no such association was present for those prescribed the reduced dose (2.5 mg twice daily).SummaryDOACs may be used after appropriate dose adjustment for an established clinical indication in patients with advanced CKD. Quality evidence for oral anticoagulation, with any specific agent or dose, for stroke prevention in hemodialysis continues to be lacking.
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Project description:Recurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy.
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Project description:ImportanceLiterature indicates adverse effects of lithium on thyroid and kidney function. However, existing data are heterogeneous, with limitations in quality and lack evaluation of adverse effects of lithium vs other mood stabilizers, especially commonly prescribed second-generation antipsychotics. Lithium serum level thresholds associated with thyroid and kidney abnormalities remain unknown.ObjectiveTo examine risk of thyroid and kidney dysfunction in patients with incident bipolar disorder (BD) treated with lithium and other mood stabilizers and antipsychotics in an Asian population and to determine lithium serum level cutoffs associated with these physical complications.Design, setting, and participantsThis population-based retrospective cohort study identified patients aged 15 years or older with first-diagnosed BD in Hong Kong from 2002 to 2018, utilizing a medical record database of public health care services. Data analysis was performed from February to May 2024.ExposuresLithium vs nonlithium treatment. The nonlithium group was further stratified into valproate, olanzapine, quetiapine, and risperidone groups.Main outcomes and measuresMain outcomes were hypothyroidism, hyperthyroidism, and chronic kidney disease stage 3 or higher (CKD3+), with additional investigation on CKD stage 4 or higher (CKD4+) and end-stage kidney disease (ESKD). Outcomes were ascertained using laboratory test results. Cox proportional hazards regression analyses were performed for risk estimation with adjusted hazard ratios (aHRs) and 95% CIs. Receiver operating characteristic analyses with the Youden index were employed to determine lithium serum level cutoffs associated with thyroid and kidney dysfunction.ResultsThere were 4752 individuals with analyzable data for hypothyroidism (mean [SD] age, 39.5 [15.6] years; mean [SD] follow-up, 8.4 [4.8] years; 2889 female [60.8%]), 4500 with data for hyperthyroidism (mean [SD] age, 39.7 [15.6] years; mean [SD] follow-up, 8.7 [4.7] years; 2716 female [60.4%]), and 7029 with data for CKD (mean [SD] age, 37.9 [14.8] years; mean [SD] follow-up, 8.3 [4.8] years; 4251 female [60.5%]). Lithium was associated with increased risk of hypothyroidism (aHR, 2.00; 95% CI, 1.72-2.33) and CKD3+ (aHR, 1.35; 95% CI, 1.15-1.60), but not CKD4+ or ESKD, compared with nonlithium treatments. Higher lithium serum levels were associated with elevated rates of hypothyroidism (aHR, 2.08; 95% CI, 1.67-2.59), hyperthyroidism (aHR, 1.81; 95% CI, 1.31-2.50), and CKD3+ (aHR, 2.11; 95% CI, 1.57-2.85). Greater number of lithium toxicity episodes was associated with increased CKD3+ risk. Valproate, olanzapine, quetiapine, and risperidone generally exhibited reduced likelihood of thyroid dysfunction and CKD3+ compared with lithium, without any difference in advanced CKD. Mean lithium serum levels greater than 0.5028 mEq/L, greater than 0.5034 mEq/L, and greater than 0.5865 mEq/L represented thresholds associated with hypothyroidism, hyperthyroidism, and CKD3+, respectively.Conclusions and relevanceIn this cohort study of patients with incident BD, lithium was associated with a mildly increased risk of thyroid dysfunction and CKD in a predominantly Chinese population. The identified lithium level thresholds associated with risks of physical complications may facilitate the development of evidence-based guidelines recommending lithium treatment, particularly in Asian populations, and the promotion of personalized care and risk-benefit balancing in the treatment for BD.
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Project description:The prevalence of HIV-associated chronic kidney disease (CKD) varies geographically and depends on the definition of CKD used, ranging from 4.7% to 38% globally. The incidence, however, has decreased with the use of effective combined antiretroviral therapy (cART). A wide variety of histological patterns are seen in HIV-associated kidney diseases that include glomerular and tubulointerstitial pathology. In resource-rich settings, there has been a plateau in the incidence of end-stage renal disease secondary to HIV-associated nephropathy (HIVAN). However, the prevalence of end-stage renal disease in HIV-positive individuals has risen, mainly due to increased longevity on cART. There is a disparity in the occurrence of HIVAN among HIV-positive individuals such that there is an 18- to 50-fold increased risk of developing kidney disease among HIV-positive individuals of African descent aged between 20 and 64 years and who have a poorer prognosis compared with their European descent counterparts, suggesting that genetic factors play a vital role. Other risk factors include male sex, low CD4 counts, and high viral load. Improvement in renal function has been observed after initiation of cART in patients with HIV-associated CKD. Treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker is recommended, when clinically indicated in patients with confirmed or suspected HIVAN or clinically significant albuminuria. Other standard management approaches for patients with CKD are recommended. These include addressing other cardiovascular risk factors (appropriate use of statins and aspirin, weight loss, cessation of smoking), avoidance of nephrotoxins, and management of serum bicarbonate and uric acid, anemia, calcium, and phosphate abnormalities. Early diagnosis of kidney disease by screening of HIV-positive individuals for the presence of kidney disease is critical for the optimal management of these patients. Screening for the presence of kidney disease upon detection of HIV infection and annually thereafter in high-risk populations is recommended.
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Project description:The association between lithium use and chronic kidney disease (CKD) needs further evaluation. We aimed to investigate this association using Danish nationwide healthcare registers and routinely collected plasma creatinine measurements from the Funen Laboratory Cohort. We conducted a case-control study nested within the population of Funen, 2001-2015. Incident cases of CKD (estimated glomerular filtration rate <60 ml/min/1.73m2 ; n = 21 432) were matched with four CKD-free controls on age, sex and calendar time (n = 85 532). We estimated odds ratios (OR) for the association between lithium exposure and CKD using conditional logistic regression models, adjusted for known risk factors for CKD. Ever-use of lithium was associated with an increased risk of CKD (adjusted OR [aOR]: 1.57; 95% confidence interval [CI]: 1.33-1.85). A stronger association was seen with current use of lithium (aOR: 1.92; 95%CI: 1.58-2.33) and long-term use of lithium (>10 years: aOR: 3.02; 95%CI: 2.00-4.56). Furthermore, we found evidence of a dose-response relationship between cumulative dose of lithium and the risk of CKD. In conclusion, the use of lithium, especially long-term, is associated with an increased risk of CKD, although the extent to which detection bias and confounding by indication contribute to the association is unclear. Monitoring of kidney function in lithium users remains mandatory to identify individuals in which switching to alternative medications should be considered.
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