Annotated Abstracts of Journal Articles
2015, 4th Quarter
Annotations by Paula Zimbrean, MD, FAPM and Marta Novak, MD, PhD
January 2016
Also of interest:
ANNOTATION (Zimbrean & Novak)
The Finding: Chronic lithium therapy for affective disorders without episodes of toxicity was not associated with a decline of renal function. The mean duration of lithium treatment was 55 months.
Strengths and Weaknesses: This is a retrospective cohort study of patients with affective disorder and a minimum of 6 months exposure to lithium therapy. The annual decline in eGFR in patients exposed to lithium did not differ compared to patients without exposure to this medication. A limitation of the study is that potential bias might have arisen from the exclusion of patients with schizophrenia or diagnoses other than affective disorders. The study also did not control for nutritional status and body mass index (BMI), nor for use of atypical antipsychotics which have recently been linked to acute kidney injury.
Relevance: This finding suggests that patients with affective disorders can receive long term treatment with lithium without significant impact upon their renal function.
Background: For more than 40 years, the long-term effect of lithium maintenance therapy on renal function has been debated. We aimed to assess the effect of lithium maintenance therapy on estimated glomerular filtration rate (eFGR) in patients with affective disorders, and explore predictors for a decrease in eGFR.
Methods: This population-based cohort study included adult patients (18-65 years of age at baseline) in Tayside (Scotland, UK) who had recently started on lithium maintenance treatment between Jan 1, 2000, and Dec 31, 2011 (retrospectively assigned to the lithium group) or those with exposure to other first-line drugs used in the treatment of affective disorders (quetiapine, olanzapine, and semisodium valproate) during the same period (retrospectively assigned to the comparator group). Patients had to have at least 6 months of (incidence) exposure to lithium or any of the comparator drugs, at least two eGFR values available in the observation period (one at baseline and at least one after ≥6 months post baseline). We excluded patients with previous exposure to lithium or one of the comparator drugs, those with a previous diagnosis of schizophrenia or other psychotic disorder, those with glomerular disease, tubulo-interstitial disease, or chronic kidney disease stages 4-5 at baseline, and those who had undergone renal transplant before exposure. Maximum follow-up was 12 years. Data were provided by the University of Dundee Health Informatics Centre, who have access to health-related population-based datasets containing data for every patient registered with a regional family doctor. Each patient has a unique ten-digit identifier, the Community Health Index, enabling us to link laboratory tests, dispensed community prescriptions, Scottish Morbidity Records, and mortality records to the patient. All data were anonymised according to Health Informatics Centre standard operating procedures. The primary outcome was the change per year in the eGFR, adjusted for age, sex, and baseline eGFR, and analysed by random coefficient models.
Findings: 1120 patients (305 exposed to lithium and 815 to comparator drugs) qualified for inclusion, providing 13 963 eGFR values over 12 years. The mean duration of exposure to lithium was 55 months (SD 42; range 6-144). Mean annual decline in eGFR (adjusted for age, sex, and baseline eGFR) was 1·3 mL/min per 1·73 m(2) (SE 0·2) in the lithium group, which did not differ significantly to that in the comparator group (0·9 mL/min/1·73 m(2) [SE 0·15]). After adjustment for additional confounders, the monthly decline in eGFR attributable to lithium exposure amounted to 0·02 mL/min per 1·73 m(2) (SE 0·02, p=0·30). As a post-hoc secondary outcome, we estimated the annual decline in eGFR for the lithium group to be 1·0 mL/min per 1·73 m(2) (SE 0·2), which again did not differ significantly to that in the comparator group (0·4 mL/min/1·73 m(2) [SE 0·2]. Modelling identified significant predictors for eGFR decline as age, baseline eGFR, comorbidities, co-prescriptions of nephrotoxic drugs, and episodes of lithium toxicity; however, duration of exposure to lithium and mean serum lithium level were not significant predictors for eGFR decline.
Interpretation: Our analysis suggests no effect of stable lithium maintenance therapy (lithium levels in therapeutic range) on the rate of change in eGFR over time. Our results therefore contradict the idea that long-term lithium therapy is associated with nephrotoxicity in the absence of episodes of acute intoxication and that duration of therapy and cumulative dose are the major determinants of toxicity.
ANNOTATION (Zimbrean & Novak)
The Finding: Psychological distress, negative beliefs about fatigue, and unhelpful behaviours (all-or-nothing behaviour or avoidance) explained 36.4% of the variance of fatigue in patients on hemodialysis. Fatigue did not correlate with hemoglobin levels, serum albumin, or dialysis vintage.
Strengths and Weaknesses: This is a cohort study of 174 patients receiving hemodialysis who were assessed for fatigue, fatigue perceptions, symptom beliefs, and work and social adjustment scale. The study did not report the role of medications or formal psychiatric diagnosis (such as major depressive disorder) in perception of fatigue.
Relevance: The findings of this study support the role of psychosocial factors in the intensity of fatigue.
Purpose: Fatigue is commonly experienced in end-stage kidney disease (ESKD) and is associated with poor outcomes. Currently, little research has examined the psychosocial correlates of fatigue severity and its impact on renal disease patients. We predicted that psychological factors (distress, cognitions and behaviours) would be associated with fatigue severity and impairment in ESKD patients even when controlling for clinical and disease factors.
Method: One hundred seventy-four haemodialysis patients completed the Chalder Fatigue Questionnaire (fatigue severity) and the Work and Social Adjustment Scale (fatigue-related impairment) in addition to measures evaluating distress, fatigue perceptions, symptom beliefs and behaviours. Demographic and clinical data were also collected.
Results: Fatigue severity was not related to haemoglobin levels, serum albumin or dialysis vintage. In hierarchical regression models, demographic and clinical factors explained 20% of the variance in fatigue (ethnicity, body mass index, exercise, log C-reactive protein and multimorbidity). Psychological distress (beta=0.21, p<0.01), negative beliefs about fatigue (beta=0.10, p=0.01) and unhelpful behaviours (all-or-nothing behaviour [beta=0.28, p<0.01] and avoidance [beta=0.16, p<0.01]) explained an additional 36.4% of the variance. Fatigue-related impairment was associated with psychological distress, perceptions that symptoms indicate damage, avoidance behaviour and the level of fatigue severity.
Conclusion: Patients’ mood, beliefs and behaviours are associated with fatigue in dialysis patients. Psychological interventions to alter these factors may reduce fatigue severity and fatigue-related disability in ESKD patients.
ANNOTATION (Zimbrean & Novak)
The Finding: Compared to the general population, patients with schizophrenia were less likely to develop ESRD. Patients with schizophrenia at the pre-ESRD stage received suboptimal pre-dialysis renal care (were less likely to visit nephrologists, received fewer erythropoietin prescriptions) and had a higher risk of hospitalization in the first year after starting dialysis.
Strengths and Weaknesses: This is a cohort study of a national database of ESRD patients which compared the incidence of ESRD, the mortality, and the medical care of ESRD patients with schizophrenia and ESRD patients without schizophrenia. The main limitation of the study is lack of evaluation of the treatment factor (patients who were receiving treatment for schizophrenia versus those who were not).
Relevance: This study points toward a need for a closer collaboration between psychiatrists and nephrologists or internists to minimize the gaps in quality of general care for patients with schizophrenia and ESRD.
Schizophrenia is closely associated with cardiovascular risk factors which are consequently attributable to the development of chronic kidney disease and end-stage renal disease (ESRD). However, no study has been conducted to examine ESRD-related epidemiology and quality of care before starting dialysis for patients with schizophrenia. By using nationwide health insurance databases, we identified 54,361 ESRD-free patients with schizophrenia and their age-/gender-matched subjects without schizophrenia for this retrospective cohort study (the schizophrenia cohort). We also identified a cohort of 1,244 adult dialysis patients with and without schizophrenia (1:3) to compare quality of renal care before dialysis and outcomes (the dialysis cohort). Cox proportional hazard models were used to estimate the hazard ratio (HR) for dialysis and death. Odds ratio (OR) derived from logistic regression models were used to delineate quality of pre-dialysis renal care. Compared to general population, patients with schizophrenia were less likely to develop ESRD (HR = 0.6; 95% CI 0.4-0.8), but had a higher risk for death (HR = 1.2; 95% CI, 1.1-1.3). Patients with schizophrenia at the pre-ESRD stage received suboptimal pre-dialysis renal care; for example, they were less likely to visit nephrologists (OR = 0.6; 95% CI, 0.4-0.8) and received fewer erythropoietin prescriptions (OR = 0.7; 95% CI, 0.6-0.9). But they had a higher risk of hospitalization in the first year after starting dialysis (OR = 1.4; 95% CI, 1.0-1.8, P < .05). Patients with schizophrenia undertaking dialysis had higher risk for mortality than the general ESRD patients. A closer collaboration between psychiatrists and nephrologists or internists to minimize the gaps in quality of general care is recommended.
