Risk factors for polyuria in a cross‐section of community psychiatric lithium‐treated patients

Background and objectives. Chronic lithium treatment in individuals with bipolar disorder can induce nephrogenic diabetes insipidus. However, the prevalence, kinetics and mechanisms of such complication are poorly known. We aimed at evaluating patterns of urine concentrating ability and the correlates of 24-hour urine output in individuals treated with lithium. Design, setting, participants and measurements. Prospective single center observational study of 217 consecutive individuals treated with lithium carbonate and referred to the renal unit. All individuals collected 24-hour urine the day before admission and underwent a desmopressin (DDAVP) concentrating test, fasting plasma vasopressin measurement (copeptin measurement in a subset of individuals, n=119), and measured GFR (mGFR) using urinary 99Tc-DTPA clearance. Maximal urine osmolality (Max Uosm) was defined as the highest level during the DDAVP test. Results. 21% of individuals displayed polyuria (> 3l/day), but 55% displayed elevated fasting vasopressin level (> 5 pg/ml). During the DDAVP test, Uosm was significantly lower, and urinary output and free water clearance were significantly higher in the highest treatment duration tertile (> 10 years) whereas no difference was observed between the first two tertiles (< 2.5 years and 2.5-10 years). Among individuals with normal Max Uosm (>600 mOsm/KgH2O) (n=128), 51% displayed elevated vasopressin levels, which was associated with higher lithium daily doses (950 [750- 1200] versus 800 [500- 1000] mg/d, p<0.001), and 100% of patients with lithium daily dose ≥1400 mg/d had high vasopressin levels. In multivariable analysis, 24-hour urine output was associated with higher lithium daily dose (beta 0.49 +/- 0.17, p=0.005), female sex (beta -359 +/- 123, p=0.004), daily osmolar intake (beta 2.21 +/- 0.24, p<0.001), maximal urine osmolality (beta -2.89 +/- 0.35, p<0.001) and plasma vasopressin level (beta 10.17 +/- 4.76, p=0.03), but not with lithium formulation. Conclusions. Higher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce renal resistance to vasopressin in these patients.

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Section: Discussionsupporting

confidence: 86%

Chronic lithium therapy and urine concentrating ability in individuals with bipolar disorder: association between daily dose and resistance to vasopressin and polyuria

Tabibzadeh

Vidal‐Petiot

Cheddani

et al. 2022

Preprint

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“…Nevertheless, we found a significant relationship between urine output and lithium daily dose, independently of other factors including lithium treatment duration, as described by Kinahan et al 33 As expected, MaxUosm was also a major determinant of urine output, which might be at least partly related to lithium treatment duration, explaining the absence of association between treatment duration and urinary output in the multivariable analysis. 20 Daily osmolar intake, estimated by the 24-hour urine osmolality, was also a determinant of urine output, suggesting lowering salt and protein intake in individuals with lithium-induced NDI may be advised to lower urine output in clinical practice.…”

Section: Clinical Researchsupporting

confidence: 85%

Chronic Lithium Therapy and Urine-Concentrating Ability in Individuals With Bipolar Disorder: Association Between Daily Dose and Resistance to Vasopressin and Polyuria

Tabibzadeh

Vidal‐Petiot

Cheddani

et al. 2022

Kidney International Reports

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“…< 700 mOsm/kg) under similar 8–10-h water restriction periods, has been termed as “partial NDI” [ 25 ]. The overnight water restriction urine osmolality has relatively high sensitivity/specificity for NDI compared to the gold-stander 24-h urine collection, particularly in combination with self-reported fluid intake, which we are also measuring [ 31 ]. In addition, we plan to complete a sub-group analysis of patients with a urine osmolality < 300 mOsm/Kg.…”

Section: Discussionmentioning

confidence: 99%

“…This short-period water restriction was selected given that longer periods of water restriction are often poorly tolerated by patients, especially those on lithium treatment [ 30 ]. Clinically, the 10-h water restriction assessment of urine osmolality is often used and is highly specific and sensitive for NDI [ 25 , 31 , 32 ]. We will assess the raw urine osmolality value at 12-weeks, adjusted for baseline.…”

Section: Methodsmentioning

confidence: 99%

“…Assessment of aquaporin excretion in urine will be indicative of the expression of the aquaporin channels and water reabsorption capabilities of the kidneys, allowing further confirmation of whether: 1) NDI pathology is present and 2) whether it is being modified by atorvastatin treatment. Furthermore, changes in daily fluid intake have been highly correlated with both urinary osmolality and the gold-stand as a characteristic of NDI [ 30 , 31 , 36 ]. Additionally, we supplement these secondary measures with self-reported frequency of nighttime and daytime polyuria.…”

Section: Methodsmentioning

confidence: 99%

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Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial

et al. 2018

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BackgroundLithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. However, clinicians are increasingly avoiding lithium largely due to fears of renal toxicity. Nephrogenic Diabetes Insipidus (NDI) occurs in 15–20% of lithium users and predicts a 2–3 times increased risk of chronic kidney disease (CKD). We recently found that use of statins is associated with lower NDI risk in a cross-sectional study. In this current paper, we describe the methodology of a randomized controlled trial (RCT) to treat lithium-induced NDI using atorvastatin.MethodsWe will conduct a 12-week, double-blind placebo-controlled RCT of atorvastatin for lithium-induced NDI at McGill University, Montreal, Canada. We will recruit 60 current lithium users, aged 18–85, who have indicators of NDI, which we defined as urine osmolality (UOsm) < 600 mOsm/kg after 10-h fluid restriction. We will randomize patients to atorvastatin (20 mg/day) or placebo for 12 weeks. We will examine whether this improves measures of NDI: UOsm and aquaporin (AQP2) excretion at 12-week follow-up, adjusted for baseline.ResultsNot applicable.ConclusionThe aim of this clinical trial is to provide preliminary data about the efficacy of atorvastatin in treating NDI. If successful, lithium could theoretically be used more safely in patients with a reduced subsequent risk of CKD, hypernatremia, and acute kidney injury (AKI). If future definitive trials confirm this, this could potentially allow more patients to benefit from lithium, while minimizing renal risk.Trial registrationClinicalTrials.gov NCT02967653. Registered in February 2017.

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Risk factors for polyuria in a cross‐section of community psychiatric lithium‐treated patients

Cited by 11 publications

References 58 publications

Chronic lithium therapy and urine concentrating ability in individuals with bipolar disorder: association between daily dose and resistance to vasopressin and polyuria

Chronic lithium therapy and urine concentrating ability in individuals with bipolar disorder: association between daily dose and resistance to vasopressin and polyuria

Chronic Lithium Therapy and Urine-Concentrating Ability in Individuals With Bipolar Disorder: Association Between Daily Dose and Resistance to Vasopressin and Polyuria

Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial

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