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

Podocyte GSK3 is an evolutionarily conserved critical regulator of kidney function

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney functio

Clinical studies on long-term lithium treatment and kidney failure

Background: Lithium enjoys the strongest evidence among today’s mood stabilisers for long-term relapse prevention of bipolar disorders, and has been shown to reduce the risks of completed and attempted suicides. However, the benefits of lithium are restricted by its adverse side effects, the most serious being the progression of renal insufficiency to end-stage renal disease (ESRD). The risk of lithium-induced ESRD (Li-ESRD) was generally acknowledged in the 1970s. As a result of these findings, much stricter lithium treatment routines, intended to reduce the lithium burden on the kidneys, were introduced in Sweden in the early 1980s. However, the impact of these modern treatment principles remains unclear. Aims of the thesis: To estimate the prevalence of lithium-associated ESRD (ESRD from all causes in lithium users), and to evaluate the role of lithium in the pathogenesis of ESRD; to test the hypothesis that modern lithium treatment routines have eliminated the risk of Li-ESRD (lithium classified as the sole or main cause of ESRD), and to study the prevalence and extent of kidney damage during the course of long-term lithium treatment in patients who started lithium treatment after 1980. Patients and Methods: We used the Swedish Renal Registry to search for lithium-treated patients with ESRD among 2644 patients with chronic renal replacement therapy (RRT), either dialysis or transplantation, within two geographical areas in Sweden with 2.8 million inhabitants. The Swedish Prescribed Drug Register was used to estimate the number of lithium patients in the two regions. The prevalence date was December 31, 2010. We reviewed the medical records of patients with suspected Li-ESRD to verify the exposure to lithium treatment, the diagnoses of Li-ESRD according to specified criteria, and the date of starting the lithium treatment. Serum lithium and creatinine levels were retrieved for 4879 patients examined between January 1, 1981, and December 31, 2010. The estimated glomerular filtration rate (eGFR) was calculated according to the Revised Lund-Malmö equation and chronic kidney disease (CKD) stages were defined using the KDOQI guidelines. Only patients who started their lithium treatment during the study period and had at least ten years of cumulative treatment were included. Results: The prevalence of ESRD patients with RRT in the lithium user population was 15.0‰ (95% CI 9.7-20.3) and the relative risk of ESRD with RRT in the lithium user population compared with the general population was 7.8 (95% CI 5.4-11.1). No patient with Li-ESRD started lithium treatment later than 1980. There was an annual increase in median serum creatinine levels already from the first year of treatment among 630 patients treated for more than ten years. About one third of those patients had CKD stage 3-5 (eGFR <60 mL/min/1.73m2) and almost 5% reached CKD stage 4 or 5 (eGFR <30 mL/min/1.73m2). Conclusions: The thesis corroborates earlier findings that Li-ESRD is an uncommon but not rare condition and gives a reasonably well-founded estimate of its prevalence. Modern lithium treatment may have eliminated the risk of Li-ESRD, as no patient with Li-ESRD started lithium treatment later than 1980. The reduced risk of Li-ESRD is probably due to less lithium exposure with lower plasma levels and lithium discontinuance when indicated on the basis of monitoring of renal function. However, a substantial proportion of patients who are treated with lithium for more than a decade develop signs of renal dysfunction and it remains to be shown whether there is still a risk of progression to Li-ESRD, but at a slower pace than earlier. The results support continuous monitoring of kidney function during long-term lithium treatment

The nurse and Overtime, A question about loyalty?

Introduktion: Sjuksköterskor arbetar idag ett stort antal övertidstimmar vilket har negativa konsekvenser för deras hälsa. Övertid ingår i en sjuksköterskas arbete om arbetsgivaren kräver det, vilket gör att de inte alltid kan tacka nej till övertidsarbete. Idag använder många arbetsgivare övertid som en sätt att lösa en underbemanning av sjuksköterskor, vilket inte bara ger konsekvenser för sjuksköterskors hälsa, utan i längden också äventyrar patienters säkerhet. Syfte: Syftet är att granska på vilket sätt övertid drabbar sjuksköterskors hälsa negativt och med det som bakgrund undersöka varför sjuksköterskor ändå väljer att arbeta övertid. Metod: Metoden är en allmän litteraturöversikt gjord på tio vetenskapliga artiklar som har analyserats utifrån Friberg (2012). Resultat: Övertid påverkar sjuksköterskors hälsa negativt då fysiska skador, trötthet, fatigue, utbrändhet, brist på socialt liv och stress kommer som följd. Sjuksköterskor arbetar ändå övertid på grund av ett ekonomiskt beroende och för att de upplever krav på lojalitet. Slutsats: Det behövs en medvetenhet om övertidens negativa konsekvenser för att vården skall kunna behålla kompetenta sjuksköterskor

How to Create Nature : A case study on the connection between nature and culture in nature conservation projects

Människans påverkan på naturen har skapat stora problem som hotar allt liv på jorden. Den häruppsatsen tar avstamp i naturvårdsmetoden rewilding som i grunden går ut på att återskapanågonting som en gång har varit. Vi vill med den här uppsatsen uppmärksamma människansplats i naturen och på så sätt ge rewilding en bredare definition. En intervju med projektledarenför naturvårdsprojektet LIFE - Bridging the Gap (BTG) har genomförts samt en medieanalys påprojektets informationsfilmer. Det insamlade materialet har sammanställts för att sedan utföraen diskursanalys av hur naturvärden framställs i projektet och hur samband mellan natur ochkultur kan synliggöras. Resultatet visar på att rewilding framställs som frånkopplat människan,men definitionen enligt tidigare forskning går ändå att applicera på projektet. Eklandskapetframställs med kulturella värden. Vi fann att återskapande av natur även innebär återskapandeav kultur. Vilket lett fram till slutsatsen att rewilding också innebär återskapande av kultur.Man's impact on nature has created major problems that threaten our own existence as well asall life on earth. This thesis is based on the nature conservation method rewilding, which isabout recreating something that once was. With this essay, we want to draw attention to man'splace in nature and thus give rewilding a broader definition. An interview with the projectmanager for the nature restoration project LIFE - Bridging the Gap has been carried out and amedia analysis of the project's information films. The collected material has been compiled tothen perform a discourse analysis of how natural values are presented in the project. Theidentified discourses are put in a cultural theoretical perspective. The results show thatrewilding is presented as something disconnected from humans, but the definition according toprevious research can still be applied to the project. The oak landscape acquires cultural andhuman values. We found that the re-creation of nature also means the re-creation of culture.Which led to the conclusion that rewilding also means re-creating culture.

How to Create Nature : A case study on the connection between nature and culture in nature conservation projects

Människans påverkan på naturen har skapat stora problem som hotar allt liv på jorden. Den häruppsatsen tar avstamp i naturvårdsmetoden rewilding som i grunden går ut på att återskapanågonting som en gång har varit. Vi vill med den här uppsatsen uppmärksamma människansplats i naturen och på så sätt ge rewilding en bredare definition. En intervju med projektledarenför naturvårdsprojektet LIFE - Bridging the Gap (BTG) har genomförts samt en medieanalys påprojektets informationsfilmer. Det insamlade materialet har sammanställts för att sedan utföraen diskursanalys av hur naturvärden framställs i projektet och hur samband mellan natur ochkultur kan synliggöras. Resultatet visar på att rewilding framställs som frånkopplat människan,men definitionen enligt tidigare forskning går ändå att applicera på projektet. Eklandskapetframställs med kulturella värden. Vi fann att återskapande av natur även innebär återskapandeav kultur. Vilket lett fram till slutsatsen att rewilding också innebär återskapande av kultur.Man's impact on nature has created major problems that threaten our own existence as well asall life on earth. This thesis is based on the nature conservation method rewilding, which isabout recreating something that once was. With this essay, we want to draw attention to man'splace in nature and thus give rewilding a broader definition. An interview with the projectmanager for the nature restoration project LIFE - Bridging the Gap has been carried out and amedia analysis of the project's information films. The collected material has been compiled tothen perform a discourse analysis of how natural values are presented in the project. Theidentified discourses are put in a cultural theoretical perspective. The results show thatrewilding is presented as something disconnected from humans, but the definition according toprevious research can still be applied to the project. The oak landscape acquires cultural andhuman values. We found that the re-creation of nature also means the re-creation of culture.Which led to the conclusion that rewilding also means re-creating culture.