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Importance: Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy.

Objective: To quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes.

Design, Setting, and Participants: This cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden.

Exposures: New use of lithium vs new use of valproate and high (>1.0 mmol/L) vs low serum lithium levels.

Main Outcomes and Measures: Progression of CKD (composite of >30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users.

Results: The study included 10 946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35 000 routine lithium tests, only 3% of results were in the toxic range (>1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76).

Conclusions and Relevance: In this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment.

Background: Clinical guidelines recommend monitoring of creatinine and lithium throughout treatment with lithium. We here assessed the extent to which this occurs in healthcare in Sweden.

Methods: This is an observational study of all adults with bipolar disorder starting lithium therapy in Stockholm, Sweden, during 2007–2018. The main outcome was monitoring of blood lithium and creatinine at therapy initiation and/or once annually. The secondary outcome was monitoring of calcium and thyroid-stimulating hormone (TSH). Patients were followed up until therapy cessation, death, out-migration, or to the end of 2018.

Results: We identified 4428 adults with bipolar disorder who started lithium therapy and were followed up for up to 11 years. Their median age was 39 years, and 63% were women. The median duration on lithium therapy was 4.3 (IQR: 1.9–7.45) years, and the majority who discontinued therapy started another mood stabilizer soon after. Overall, 21% started lithium therapy without assessing the serum/plasma concentration of creatinine. The proportion of people who did not have both lithium and creatinine measured increased from 21% in the first year to 33% in the eleventh year. The proportion with annual testing for TSH or calcium was slightly lower. As few as 16% of patients had both lithium and creatinine tested once annually during their complete time on lithium.

Conclusions: In a Swedish community sample, lithium and creatinine monitoring was inconsistent with guideline recommendations that call for measurement of annual biomarker levels.

Dietylenglykol är en toxisk alkohol som i detaljhandeln främst förekommer i bromsvätska. 

Förloppet vid dietylenglykolförgiftning skiljer sig i viktiga avseenden från de mera kända toxiska alkoholerna etylenglykol och metanol.

Dietylenglykolförgiftningen ger få intiala symtom men kan med fördröjning orsaka irreversibla njurskador och neurologiska bortfallssymtom. 

Globalt har massförgiftningar inträffat, ibland med hundratals dödsfall, där dietylenglykol använts som lösningsmedel i läkemedel. 

Här presenteras det första kända svenska fallet av dietylenglykolförgiftning, där intag av en större mängd bromsvätska ledde till anuri, leverpåverkan, kranialnervs­påverkan och polyneuropati.

Diethylene glycol poisoning – the first known Swedish case

A woman in her sixties presented at the Emergency department with nausea, flank pain and profuse vomiting. She had an anion-gap metabolic acidosis, elevated liver enzymes and a pronounced renal failure with creatinine 1997 µmol/L (22,6 mg/dl). She was admitted and treated with haemodialysis. On hospital day 5 a bilateral facial palsy, blindness and a moderate generalized weakness rapidly developed. The patient now revealed that she had consumed about 2 dl of brake fluid with a high content of diethylene glycol about a week before hospital admission. Diethylene glycol poisoning typically causes irreversible kidney failure and demyelinating nerve damage in severe cases. The early and debilitating metabolic acidosis seen in ethylene glycol poisoning seems to be absent in diethylene glycol poisoning and patients often present late. This is the first known Swedish case of symptomatic diethylene glycol poisoning. Internationally, during the last century, several mass poisonings have been caused by diethylene glycol contaminated pharmaceutical products.