Michael Ott

Background: High interdialytic weight gain (IDWG) and ultrafiltration rate have been associated with increased mortality in patients undergoing haemodialysis. Cardiac biomarkers reflecting strain, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (TnT), are known to increase during haemodialysis sessions. Previous studies suggest that these intradialytic increases may be related to ultrafiltration rate, with a proposed threshold of 0.6 IDWG per hour. This study therefore aimed to prospectively evaluate whether reducing ultrafiltration rate attenuates the haemodialysis-associated increase in these cardiac biomarkers. Method: In this multicentre, prospective study prevalent haemodialysis patients with a relative IDWG > 2.5% of body weight and ultrafiltration rate ≥ 0.72 IDWG per hour underwent one standard and one prolonged haemodialysis session with a ≥ 20% reduction in ultrafiltration rate, targeting an ultrafiltration rate ≤ 0.6 IDWG per hour. NT-proBNP and TnT were analysed directly before dialysis, at 180 minutes, and at the end of each haemodialysis session. Results: Of 238 screened patients, 65 met the inclusion criteria and none of the exclusion criteria. Of these, 56 were enrolled and 41 included in the final analysis, meeting the pre-specified sample size required to detect a clinically relevant difference. NT-proBNP and TnT increased significantly during both dialysis sessions ( p < 0.001). However, no difference was observed in ∆NT-proBNP ( p = 0.967) or ∆TnT ( p = 0.823) between treatments with different ultrafiltration rates. Achieving an ultrafiltration rate ≤ 0.6 IDWG per hour required a mean treatment duration of 423 ± 139 minutes (min 246, max 775). Among the 12 patients (29.3%) who achieved the targeted ultrafiltration rate of ≤0.6 IDWG per hour, changes in NT-proBNP ( p = 0.062) and TnT ( p = 0.114) did not differ significantly between sessions with different ultrafiltration rates. Conclusions: In stable, prevalent haemodialysis patients who tolerate their ordinary treatment, reducing the ultrafiltration rate by at least 20% did not attenuate the increase in NT-proBNP and TnT during a single haemodialysis session. In these patients, achieving an ultrafiltration rate ≤ 0.6 IDWG/h generally required treatment durations that are not feasible in routine in-centre haemodialysis. Trial registration: Registered at clinicaltrials.gov (NCT06153888) November 6 2023 (Retrospectively registered).

Background: Long-term treatment with lithium can cause kidney damage. It has been hypothesised that single daily lithium dosing (SDD) minimizes kidney damage and SDD, given in the evening, has been widely endorsed by the medical community. However, kidney physiology suggests that SDD in the evening might maximise rather than minimise kidney damage. This review aims to assess if SDD compared with multiple daily lithium dosing (MDD) results in less kidney impairment. Methods: This PROSPERO-registered (CRD42024537460) systematic review was conducted in accordance with the PRISMA guidelines. PubMed and Web of Science were searched to identify studies investigating the effect of different lithium dosing regimens on kidney function, published up to 31 December 2024. Owing to substantial heterogeneity across studies, outcomes were synthesised narratively in accordance with the SWiM (Synthesis Without Meta-analysis) reporting guideline. Study validity was assessed across four domains: (a) kidney outcome adequacy, (b) statistical power, (c) control of confounders, and (d) methodological rigour. Certainty of evidence was evaluated using the GRADE approach. Findings: Of 709 records screened, 19 studies and one case report were included, comprising 6787 patients. The largest study, analysing 5751 patients, did not report the number of patients on SDD or MDD. The remaining studies, including the case report, included 492 patients on SDD and 576 on MDD. Only one study was of fair validity, finding no difference in kidney outcomes between dosing regimens. The remaining 18 studies and the case report were of poor validity. The certainty of evidence for SDD in terms of kidney protection was very low. Interpretation: Current evidence does not support the hypothesis that a lithium dose given as SDD in the evening, compared to MDD, is superior for the prevention or containment of kidney impairment.

Background: Haemodialysis access patterns differ internationally. This can not only be explained by differences in patient cohorts. What is considered the right access for the right patient is debated and it is unclear which patient-related factors affect the choice of access. The aim of the study was to investigate how patient-specific factors as body size and comorbidities influenced the choice of haemodialysis access in a real-life setting. Methods: Retrospective cohort study including all patients receiving a haemodialysis access in Sweden between 2013 and 2022. Data from the Swedish Renal Registry (SNR) and the National Patient Register (NPR) was used. Data regarding age, sex, cause of kidney failure, previous kidney replacement therapy, height and weight (after dialysis), were collected from SNR. Data on comorbidities were extracted both from SNR and the NPR. AV-accesses were grouped into four categories depending on location of artery. Changes in arteriovenous access creation over time and patient-related factors affecting the choice of first access were analysed. Results: Of 10,170 patients, 9706 with 17,709 accesses were included. The creation of upper-arm fistulas ( p = 0.042) and arteriovenous grafts ( p = 0.007) increased. Small body size, female sex, diabetes mellitus, vintage, previous haemodialysis treatment (all p < 0.001), age ( p = 0.002) and peripheral arterial disease ( p = 0.031) led to more central venous catheters. Small body size, female sex, peripheral arterial disease, vintage, previous haemodialysis treatment (all p < 0.001) and diabetes mellitus ( p = 0.023) decreased the probability for selecting a forearm fistula. Upper-arm fistulas were preferred over arteriovenous grafts for those with small body size ( p < 0.001 for body surface area), female sex ( p = 0.003) and previous haemodialysis ( p < 0.001). Conclusions: The use of upper-arm fistulas and arteriovenous grafts is increasing, while forearm arteriovenous fistulas remain the primary access modality. Patient-related factors influencing the choice of access seemed to be related to vessel size and quality, rather than age and cardiovascular comorbidities.

Background: Long‐term lithium treatment decreases kidney function. However, it remains unclear whether stopping lithium improves kidney function.Objectives: To study kidney function in patients who stopped and subsequently restarted lithium treatment.Methods: Mirror‐image design using data from the LiSIE retrospective cohort study. The mirror was set to when lithium was stopped with a 5‐year pre‐ and post‐mirror period. Adult patients with bipolar, schizoaffective disorder or unipolar depression, who had lithium ≥4.5 years in the pre‐mirror period, were included. Creatinine measurements were available from 1997 to 2017. The main outcome was the difference in mean annual change of the estimated glomerular filtration rate (eGFR) adjusted for sex, hypertension and diabetes mellitus.Results: A total of 168 participants (94 women, 74 men) were included. Mean annual eGFR change was −1.58 (−1.87 to −1.28) mL/min/1.73 m²/year before and −0.023 (−0.49 to +0.44) mL/min/1.73 m²/year after lithium discontinuation (p < 0.0001 for difference). The improvement was 0.77 (0.35–1.20) mL/min/173 m²/year in participants with eGFR >60 mL/min/1.73 m², and 3.03 (2.15–3.92) mL/min/1.73 m²/year for participants with eGFR 2. The effect was persistent over the 5‐year post‐mirror study period. For participants restarting lithium, the mean annual eGFR change was −1.71 (−2.26 to −1.16) mL/min/1.73 m²/year, a setback compared to their lithium‐free post‐mirror period (p < 0.0001). We did not see any difference compared to the pre‐mirror period (p = 0.51).Conclusions: Stopping lithium slowed down mean eGFR decline. This effect was more pronounced in participants with lower eGFR at the time of lithium discontinuation. In participants who restarted lithium, the annual decline of eGFR reverted to pre‐lithium discontinuation levels.

In a recent article, Liu and colleagues presented a case-series of patients with lithium poisoning, with special emphasis on hemodialysis

Background: Lithium-associated hyperthyroidism is much rarer than lithium-associated hypothyroidism. Yet, it may be of substantial clinical significance for affected individuals. For instance, lithium-associated hyperthyroidism could destabilise mood, mimic manic episodes and impact physical health. Only few studies have explored incidence rates of lithium-associated hyperthyroidism. Even fewer studies have compared incidence rates according to lithium exposure history. Objectives: To determine the impact of lithium treatment on the incidence rate of hyperthyroidism in patients with bipolar or schizoaffective disorder and assess its aetiology. Design: This study is part of the LiSIE (Lithium – Study into Effects and Side Effects) retrospective cohort study. Methods: Between 1997 and 2017, patients in the Swedish region of Norrbotten with a diagnosis of bipolar or schizoaffective disorder were screened for all episodes of overt hyperthyroidism in form of thyrotoxicosis or thyroiditis. Incidence rates of episodes of hyperthyroidism per 1000 person-years (PY) were compared in relation to lithium exposure; concurrent, previous, or no exposure ever (lithium-naïve patients) Results: In 1562 patients, we identified 16 episodes of hyperthyroidism corresponding to an incidence rate of 0.88 episodes per 1000 PY. Ninety-four percent of episodes had occurred in women. Patients who had concurrently been exposed to lithium, had an incidence rate of 1.35 episodes per 1000 PY. Patients who had previously been exposed to lithium had an incidence rate of 0.79 per 1000 PY. Patients who had never been exposed to lithium had an incidence rate of 0.47 per 1000 PY. There were no significant differences in the risk ratios for patients with concurrent or previous exposure compared with lithium-naïve patients, neither for hyperthyroidism overall, thyrotoxicosis, or thyroiditis. Conclusion: Lithium-associated hyperthyroidism seems uncommon. The risk of hyperthyroidism does not seem significantly higher in patients with current or previous lithium exposure than in lithium-naïve patients.

(1) Background: Few studies have explored the impact of lithium intoxication on the heart. (2) Methods: We examined electrocardiogram (ECG) changes associated with lithium intoxication in the framework of the LiSIE (Lithium—Study into Effects and Side Effects) retrospective cohort study. We analysed ECGs before, during, and after intoxication. (3) Results: Of the 1136 patients included, 92 patients had experienced 112 episodes of lithium intoxication. For 55 episodes, there was an ECG available at the time; for 48 episodes, there was a reference ECG available before and/or after the lithium intoxication. Lithium intoxication led to a statistically significant decrease in heart rate from a mean 76 beats/min (SD 16.6) before intoxication to 73 beats/min (SD 17.1) during intoxication (p = 0.046). QTc correlated only weakly with lithium concentration (ρ = 0.329, p = 0.014). However, in 24% of lithium intoxication episodes, there were QT prolongations. In 54% of these, QTc exceeded 500 ms; patients with chronic intoxications being more affected. (4) Conclusions: Based on summary statistics, effects of lithium intoxication on HR and QTc seem mostly discrete and not clinically relevant. However, QT prolongation can carry a risk of becoming severe. Therefore, an ECG should always be taken in patients presenting with lithium intoxication.

Dear EditorDrs. Angela Chiew and Nicholas Buckley present a review on the serotonin toxidrome in your journal [1]. We fully agree with the authors that serotonin toxicity (ST) is a clinical diagnos...

(1) Background: It has been suggested that hyperthyroxinaemia is a risk factor for lithium intoxication by altering tubular renal function. (2) Methods: We determined the relevance of hyperthyroxinaemia as a risk factor for lithium intoxication in patients with bipolar or schizoaffective disorder in the framework of the LiSIE (Lithium-Study into Effects and Side Effects) retrospective cohort study. Of 1562 patients included in the study, 897 patients had been exposed to lithium at any time between 1997 and 2017 with 6684 person-years of observation. (3) Results: There were 65 episodes of unintentional lithium intoxication in 53 patients. There were nine episodes with hyperthyroxinaemia at the time of lithium intoxication, yielding an incidence of 1.3 episodes/1000 person-years. For all nine episodes, we could identify alternative, more plausible, explanations for the observed lithium intoxications. (4) Conclusions: We conclude that hyperthyroxinaemia-associated unintentional lithium intoxication is an uncommon event. A direct causal link between hyperthyroxinaemia and altered tubular renal function remains elusive. Increasing the frequency of routine thyroid function tests seems unlikely to decrease the risk of lithium intoxication.