Journal Article Annotations
2023, 4th Quarter

Psychonephrology

Annotations by Shivali Patel, MD and Sahil Munjal, MD
January, 2024

Depression among patients with chronic kidney disease, associated factors, and predictors: a cross-sectional study.
Concurrent lithium and haemodialysis treatment: Clinical recommendations based on the literature and a multicentre survey.

Of interest:

- Key questions on the long term renal effects of lithium: a review of pertinent data.

PUBLICATION #1 — Psychonephrology

Depression among patients with chronic kidney disease, associated factors, and predictors: a cross-sectional study.

Mandreker Bahall, George Legall, Carlyle Lalla.

Abstract: BMC Psychiatry. 2023 Oct 10;23(1):733. doi: 10.1186/s12888-023-05249-y.

Background:
Depression with diverse etiologies is exacerbated by chronic diseases, such as chronic kidney disease (CKD), coronary artery disease (CAD), cancer, diabetes mellitus, and hypertension. This study aimed to analyse depression, its associations, and predictors among patients attending the kidney clinic of a teaching hospital.

Methods:
Data were collected from 01 August 2017 to 30 September 2017 via face-to-face interviews and examination of the medical records of a convenience sample of 314 patients. The patients were categorised broadly as stages I and II with an estimated glomerular filtration rate (eGFR)>60 mls/min/1.73 m2 , and with stages III, IV, and V or GFR≤60 mls/ min/1.73 m2 (or CKD). The Patient Health Questionnaire (PHQ)-9 was the data collection instrument for depression-related data.

Results:
Participants were predominantly male (n=179; 57.0%), aged over 60 years (n=211; 67.2%), Indo-Trinbagonian (n=237; 75.5%), and with stages III, IV, and V CKD. The two leading comorbid conditions were hypertension (83.4%) and diabetes mellitus (56.1%). Of the 261 (83.1%) patients with recorded eGFR, 113 (43.3%) had Stage III CKD. The mean depression (PHQ-9) score was 13.0/27 (± 9.15), with 306 (97.5%) patients diagnosed as having depression with the following severities: mild (n=116; 37.9%), moderate (n=138, 45.1%), moderately severe (n=38; 12.4%), and severe (n=14; 4.6%). Depression was independent of sex. Nine sociodemographic variables were associated with depression; however, ‘level of education’, was the only predictor of depression with greater severity associated with lower levels of education. eGFR was negatively correlated with the PHQ-9 scores (Pearson’s correlation, r = -0.144, p=0.022). At least 78.3% of the patients who self-reported no depression had clinical depression (moderate, moderately severe, or severe) PHQ-9 scores≥10.

Conclusion:
Depression was a significant comorbidity among patients with CKD, with the majority displaying clinical depression. “Level of education” was the only predictor of depression. Self-reported depression is an unreliable method for evaluating clinical depression.

Annotation

The finding:
Although patients with chronic kidney disease also have clinical depression, many of these individuals (over 75% of this study’s sample) did not self-report depression or depressive symptoms. The study found that lower levels of education was the only predictor for greater depression severity despite other sociodemographic variable that were associated with depression.

Strength and weaknesses:
While the study made use of the PHQ-9, a reliable and valid tool to determine depressive severity, and aimed to capture important factors associated with depression on the screening instrument, there were several limitations. There was a relatively small sample size with limited generalizability, as most individuals included were male, over age 60, of Indo-Trinbagonian ethnicity, had family and/or social support, and were on government assistance. Moreover, this was a convenience sample, taken from individuals referred to the chronic kidney disease clinic. Apart from hypertension and diabetes mellitus, other potentially contributory medical conditions, substance use disorders, and use of medications were unknown.

Relevance:
C-L psychiatrists should be aware of the high prevalence of depression among patients with chronic kidney disease and the negative correlation between estimated glomerular filtration rate and PHQ-9 scores. Many patients with chronic kidney disease who have clinical depression may not voluntarily share their symptoms, so it is essential for psychiatrists to educate our nephrology colleagues on the importance of routinely screening patients for depression and referring for treatment when deemed clinically appropriate.

PUBLICATION #2 — Psychonephrology

Concurrent lithium and haemodialysis treatment: Clinical recommendations based on the literature and a multicentre survey.

Wytse J Kuiper, Koen P Grootens, Angèle P M Kerckhoffs.

Abstract: Bipolar Disord. 2023 Nov 15. doi: 10.1111/bdi.13390. Online ahead of print.

Introduction:
Lithium has an irreplaceable role in the treatment of severe mood disorders, but declining renal function associated with its use leads to clinical dilemmas. Although not often applied, and requiring close monitoring and multidisciplinary actions, concurrent lithium and haemodialysis treatment (CLHT) is a feasible option. To our knowledge, however, there are no detailed consensus- or evidence-based treatment guidelines or directives on its delivery.

Methods:
To fill this gap, we reviewed the literature and surveyed psychiatrists and nephrologists with experience in CLHT using a self-designed questionnaire. Our goal was to form an integrated picture of the current knowledge and clinical practices of CLHT and formulate practical recommendations for colleagues being confronted with patients with renal dysfunction requiring lithium to help manage their mood disorder.

Results:
We identified 14 case reports and case series describing CLHT and one systematic review concluding CLHT to be effective. Ten nephrologists and six psychiatrists practising in the Netherlands completed our questionnaire, providing details on collaboration, lithium dosing regimens, serum level evaluations and additional amenities and services they deemed necessary during CLHT delivery.

Discussion:
We found that CLHT appears to be safe and effective and argue that delivery is a shared responsibility and needs continuous multidisciplinary finetuning. To facilitate delivery, we provide a flowchart for the initiation or reinstatement of lithium therapy in haemodialysis patients and a practical guide for CLHT, including an easy-to-use rule of thumb for calculating the lithium target dose.

Annotation

The finding:
The study reviewed evidence of concurrent lithium and hemodialysis treatment (CLHT), using a conventional PubMed search along with a survey of current practices among nephrologists and psychiatrists to arrive at a practice guideline. The authors propose a calculation for target dose (mg), which can be determined as follows: 10 × body weight (kg) × target concentration (mmol/L). Per the evidence reviewed, lithium is taken on dialysis days only, immediately after dialysis. However, prescribing lithium on non-dialysis days may be necessary in cases with residual diuresis. It is important to note residual renal function is common in lithium-induced nephropathy leading to fluctuation of levels. The authors recommend trough levels to be assayed before each dialysis session until stable for at least three consecutive measurements, before reducing monitoring frequency to monthly. Using a flowchart, they highlight the steps in starting and/or continuing lithium in hemodialysis patients along with a proposed formula calculating lithium target dosing.

Strength and weaknesses:
Evidence was limited to case reports/series with a significant risk of publication bias. Also, there were only 16 respondents to the survey which was sent out to providers in Netherlands. It may not be generalizable to other places. Survey only included items pertaining to regimen chosen rather than the rationale.

Relevance:
The paper offers much needed practical guidance for CL psychiatrists on the safely of combining lithium and haemodialysis. Close multidisciplinary collaboration between psychiatrists and nephrologists are essential. Additional lithium measurements are advised in case of changes in dialysis schedule, residual diuresis, adverse effects, changes in co-medication, fluid intake, warm weather, and other potentially relevant events.

PUBLICATION #3 — Psychonephrology

Key questions on the long term renal effects of lithium: a review of pertinent data.

Michael Gitlin, Michael Bauer.

Abstract: Int J Bipolar Disord. 2023 Nov 16;11(1):35. doi: 10.1186/s40345-023-00316-5.

For over half a century, it has been widely known that lithium is the most efficacious maintenance treatment for bipolar disorder. Despite thorough research on the long-term effects of lithium on renal function, a number of important questions relevant to clinical practice remain. The risk of polyuria, reflecting renal tubular dysfunction, is seen in a substantial proportion of patients treated with long term lithium therapy. The duration of lithium may be the most important risk factor for lithium-induced polyuria. Most, but not all, studies find that lithium is associated with higher rates of chronic kidney disease compared to either age matched controls or patients treated with other mood stabilizers. Age, duration of lithium therapy and medical disorders such as hypertension and diabetes mellitus are risk factors for chronic kidney disease in lithium-treated patients. The relationship between polyuria and chronic kidney disease is inconsistent but poorly studied. Although not all studies agree, it is likely that lithium may increase the risk for end stage renal disease but in a very small proportion of treated patients. Patients whose renal function is relatively preserved will show either no progression or improvement of renal function after lithium discontinuation. In contrast, patients with more renal damage frequently show continued deterioration of renal function even after lithium discontinuation. Optimal management of lithium treatment requires obtaining a baseline measure of renal function (typically estimated glomerular filtration rate [eGFR]) and regular monitoring of eGFR during treatment. Should the eGFR fall rapidly or below 60 ml/minute, patients should consider a consultation with a nephrologist. A decision as to whether lithium should be discontinued due to progressive renal insufficiency should be made using a risk/benefit analysis that takes into account other potential etiologies of renal dysfunction, current renal function, and the efficacy of lithium in that individual patient.

Annotation (unstructured)

This review summarized recent literature regarding the long-term effects of lithium on kidneys. Risk factors for lithium-induced renal disease include length of exposure to lithium, previous episodes of lithium toxicity, elevated lithium levels, use of other psychotropic medications, comorbid medical disorders, female sex, and history of migraines. Individuals with higher serum creatinine before beginning lithium treatment are more likely to progress to chronic kidney disease stage IV or V compared to those with normal serum creatinine levels before beginning lithium treatment. Additionally, estimated glomerular filtration rate at the time of lithium discontinuation, serum creatinine >2.5 mg/dl, and a creatinine clearance cut-point of 40 ml/min may be important variables to consider when assessing the risk and trajectory of renal deterioration following lithium discontinuation.