Journal Article Annotations
2025, 1st Quarter

Psychonephrology

Annotations by Shivali Patel, MD and Rebekah Nash, MD PhD
March, 2025

Prospects for lithium treated patients with severe renal impairment.
Depression and anxiety in people with kidney disease: understanding symptom variability, patient experience and preferences for mental health support.

Of interest:

Lithium and Kidney Disease.

PUBLICATION #1 — Psychonephrology

Prospects for lithium treated patients with severe renal impairment.

Harald Aiff, Per-Ola Attman, Mihaela Golic, Bernd Ramsauer, Staffan Schön, Steinn Steingrimsson, Jan Svedlund

Abstract: Int J Bipolar Disord. 2025 Feb 14;13(1):5. doi: 10.1186/s40345-025-00372-z.

Objectives:
To study the prospects for lithium treated patients who develop end stage renal disease (ESRD) and the role of renal replacement therapy (RRT).

Methods:
Retrospective analysis of survival, somatic comorbidity, lithium treatment and eligibility for renal replacement therapy in adult patients with at least one eGFR < 30 ml/min/1.73 m². Subjects were selected from our laboratory database (s-Lithium and s-creatinine) from 1980 to 2017.

Results:
620 (14%) of 4396 patients with a lithium history had at least one measurement of eGFR < 30 ml/min/1.73 m². 302 (49%) patients had a transient decrease in renal function with subsequent improvement, 135 (22%) patients died with acute renal failure, while 153 (25%) developed chronic kidney disease stage 4 (CKD4) and 33 (5%) required RRT. RRT-treated patients represent only a fraction of the total ESRD population. Median survival time from the debut of CKD4 was 13.9 years in patients < 65 years and 4.4 years in older patients. 100 of the 153 patients with CKD4 continued lithium treatment. There was no significant difference in survival after the debut of CKD4 between the patients who stopped lithium treatment and those who continued.

Conclusions:
A measurement of eGFR < 30 ml/min/1.73 m² reflects a significant loss of renal function. In half of the patients it was due to a transient functional disturbance without long-term consequences. A quarter of patients had acute renal failure and died within days while the remaining quarter progressed to CKD4. Despite irreversible renal damage, patient survival can be counted in several years after debut of renal insufficiency with appropriate care including RRT. As the treating psychiatrist, it is important to consult with nephrology when renal function starts to deteriorate, to optimise somatic treatment

Annotation

The finding:
This was a retrospective study analyzing the potential outlook and implications for patients aged 18 and older who were treated with lithium and had at least one measurement demonstrating significant renal insufficiency (eGFR<30 m/min). This study, which included 620 patients and analyzed data from individual medical charts in a Swedish Hospital as well as the Swedish National Cause of Death Register, the Swedish Renal Register, and the Swedish Death Index between January 1, 1980 to December 31, 2017, found that 467 patients never reached CKD-IV (chronic kidney disease), 153 patients reached CKD-IV, and 98 patients reached CKD-V. In patients who did not reach CKD-IV by the end of the study period, nearly half had transient impairment and ultimately recovered renal function and over 20% died within the first 90 days of the debut of eGFR<30 ml/min from fatal hemodynamic imbalance. In patients who reached CKD-IV or CKD-V, mean survival time after initial diagnosis was highly correlated with and decreased with age; many of these patients also had somatic comorbidities such as cardiovascular disease, diabetes mellitus, malignancy, urological condition, or a co-existing or pre-existing renal disease. Moreover, 100 patients were still treated with lithium at the time of CKD-IV diagnosis and 68 patients continued lithium for more than one year after CKD-IV diagnosis; further decline of the eGFR was not found to be affected by discontinuation of lithium. Thirty-three patients with CKD-V underwent renal replacement therapy, with six ultimately going onto receive transplantation.

Strength and weaknesses:
Most individuals in this naturalistic cohort study had somatic comorbidities like diabetes mellitus and vascular disease which could predispose to increased risk of nephropathy—this may often be encountered in lithium-treated patients, and thus the results can be viewed as generalizable. The study also focused on a wide age range of patients and analyzed outcomes in patients who experienced a significant decline in eGFR which could not be explained by age alone. Moreover, there was a long follow-up period so authors could assess not only the direct impact of lithium on renal function but long-term implications. While there was extensive data gathered from different sources, thoroughness and accuracy of reported results were dependent on the completeness of the medical record; and because the authors noted that there was a limited influx of data during the first decade of the study period, this may have skewed the results. In addition, patients who moved out of the catchment area by the end of the study period may have gone onto develop CKD-IV or CKD-V, though were lost to follow-up and were not included in the final analysis. Finally, it is not clear if there were other factors which may have contributed to nephropathy and confounded the results such as use of nephrotoxic agents, nephrogenic diabetes insipidus, and prior episodes of lithium toxicity.

Relevance:
While nephropathy is a known potential adverse effect of lithium, less is known about possible outcomes in lithium-treated patients who develop a significant decline in eGFR. This study found that about 15% of lithium-treated patients experienced a transient or chronic decline in renal function throughout the course of lithium treatment and importantly shed light on the clinically significant implications of this functional decline. Because the magnitude of risks associated with continued lithium use in individuals with renal insufficiency vary and discontinuation of lithium does not necessarily reverse or slow the decline of renal function, it is important for psychiatrists to carefully monitor serum creatinine and glomerular function rate trajectories over time, thoughtfully weigh risks of untreated psychiatric illness against risks of further renal damage, and consult with nephrologists in a timely manner.

PUBLICATION #2 — Psychonephrology

Depression and anxiety in people with kidney disease: understanding symptom variability, patient experience and preferences for mental health support.

Joseph Chilcot, Christina J Pearce, Natalie Hall, Zara Rehman, Sam Norton, Sophie Griffiths, Joanna L Hudson, Lucy Mackintosh, Amanda Busby, David Wellsted, Julia Jones, Shivani Sharma, Paula Ormandy, Nick Palmer, Pooja Schmill, Maria Da Silva-Gane, Neal Morgan, Dimitrios Poulikakos, Kristin Veighey, Stuart Robertson, Rob Elias, Ken Farrington.

Abstract: J Nephrol. 2025 Mar;38(2):675-686. doi: 10.1007/s40620-024-02194-1. Epub 2025 Jan 12.

Background:
Depression and anxiety are commonly experienced by people with chronic kidney disease (CKD). This study aimed to evaluate person- and service-level factors associated with depression and anxiety symptoms. We sought to also understand utilisation of mental health treatments and preferences for future psychological support.

Methods:
An online survey recruited participants from six UK kidney services with varying levels of psychosocial provision. The survey was also advertised on social media. Participants completed screening questionnaires for depression and anxiety, alongside questions about mental health history, self-efficacy, treatment and support. The study included adults (18 years or older) living with CKD (stages 3b and above) or those receiving any form of Kidney Replacement Therapy (KRT), including individuals with a functioning kidney transplant. Eligible participants had to complete study measures and be proficient in reading and writing in either English or Welsh, as the survey was administered in these languages. This survey was developed with our Patient and Public Involvement group and was administered from January 2023 until 31st January, 2024 using Qualtrics and RedCap.

Results:
Four hundred fifty-eight people completed the survey. Moderate-severe symptoms of depression and anxiety were 37.7% and 26.5%, respectively. Over 50% reported a history of diagnosed depression. In addition to depression, sleep problems and fatigue were identified as future support needs, with over a third indicating a preference for in-centre provision. In case-mix adjusted analysis, there was no variability in depression and anxiety symptoms across centres. Centre location and size were unrelated to symptoms. Age, female gender, current mental health treatments, self-efficacy and perceptions regarding opportunity for support, were associated with symptoms of depression and anxiety. In sub-analysis, there was a negative association between psychosocial staffing levels and depression symptoms.

Conclusion:
Patient-related factors and behavioural characteristics were related to variation of these symptoms. There was little evidence of symptom variability across centres, although in a small sub-analysis, psychosocial provision showed a weak negative correlation with depression symptoms. Our findings highlight preferences of future needs which could be helpful for designing future research and service provision.

Annotation

The finding:
In this cross-sectional survey-based study in the UK, a cohort of clinic- (n=197) and online- (n=261) recruited patients with chronic kidney disease (CKD) (stage 3b or higher) or a kidney transplant (KT) reported a high prevalence of depression symptoms (56.5%), anxiety symptoms (40.6%), antidepressant use (35.5%), and moderately high engagement with talk therapy (27.9%) over the preceding year. The authors also described factors associated with depression and anxiety in the cohort (e.g., age, female gender, mental health efficacy, and engagement in talk therapy or antidepressant use). Clinic-specific characteristics did not impact depression or anxiety prevalence, outside of a weak negative association between number of psychosocial professionals at a clinic and depression symptoms during subgroup analyses. When asked, the participants endorsed a desire for psychological support for depression, anxiety, insomnia, and fatigue. There were highly significant differences in demographics and clinical characteristics between the clinic- and online-recruited participants, for which the authors attempted to correct; notably, there were no subgroup analyses comparing participants with CKD versus those with a KT.

Strength and weaknesses:
The majority of participants were recruited using social media advertising; as it was unclear from the methods if these individuals were screened by study staff, this recruitment method risked inclusion of non-CKD patients, duplicate entries, and violation of the stated inclusion/exclusion criteria. Additionally, the cohort included both CKD (3b and above) and KT recipients, which are distinct populations with unique distributions of physical- and psychiatric-symptom burden; these distinct patterns of symptoms may have been obscured by combining the two populations. Moreover, data were generated from self-report surveys; this data collection method is both a weakness (the data are not verified by clinical evaluation or medical record review) and a strength (symptoms are less likely to be under-reported). Finally, the surveys collected a very impressive level of detail regarding treatment history; however, asking participants to recall this level of detail could increase the risk of recall bias/poor recall by participants.

Relevance:
Patients with kidney disease are at increased risk for psychiatric symptoms but can experience improvement with appropriate therapies. Patients in this cohort identified depression, anxiety, insomnia, and fatigue as key areas for which they desired clinical intervention. While, as C-L psychiatrists, we are all too aware of many risk factors for depression and anxiety, these authors identified a protective factor for their cohort: “mental health self-efficacy”; the identification of protective factors for psychiatric conditions is an important next goal for the field.

PUBLICATION #3 — Psychonephrology

Lithium and Kidney Disease.

Mete Ercis, Maria L Gonzalez Suarez, Balwinder Singh.

Abstract: Mayo Clin Proc. 2025 Jan;100(1):19-25. doi: 10.1016/j.mayocp.2024.10.008. Epub 2024 Dec 5.

Annotation (Unstructured)

This commentary focuses on the impact of lithium on chronic kidney disease (CKD) and limitations of current observational studies highlighting the relationship between lithium and nephropathy. Proposed risk factors for developing CKD while on lithium therapy may depend on treatment-related factors (duration of treatment, nephrogenic diabetes insipidus, and prior episodes of lithium toxicity) and patient-related factors (demographics such as older age and female sex, medical comorbidities such as diabetes mellitus and hypertension, and concomitant medications such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers, thiazide diuretics, and non-steroidal anti-inflammatory drugs). The authors emphasize that retrospective and cross-sectional studies examining lithium’s impact on CKD may not clearly differentiate the impact of lithium on renal function versus the impact of other medications or medical comorbidities on renal function, may not include a proper control group, and may focus only on eGFR as a function of serum creatinine (which can fluctuate depending on muscle mass, hydration status, and use of certain medications) and not take into consideration other relevant biomarkers such as cystatin C. Ultimately, the authors suggest that incorporating clinical and genomic information into risk prediction models may allow for more patient-centered, individualized treatment plans to potentially avoid premature discontinuation of lithium.