Causes of CKD in People with Severe Mental Illness

Although research is limited, the available evidence demonstrates that there is a higher risk of CKD for individuals with severe mental illness (13⇓–15). This risk can be partly accounted for by a high prevalence of risk factors for CKD, such as higher rates of smoking (16), cardiovascular disease (17), and type 2 diabetes (18), as well as social determinants of health, including higher risk of food insecurity (19), social exclusion (20), and homelessness (21). However, the higher risk is still significant after controlling for these factors (13,14) (Figure 1).

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Figure 1.

Relationship between severe mental illness, CKD, and clinical outcomes.

Another important risk factor for CKD is lithium treatment (22). Lithium is a mood stabilizer used in the treatment of severe mental illness such as bipolar disorder or schizoaffective disorder (23). Lithium is nephrotoxic (22), and acute lithium toxicity can induce AKI (24). Lithium therapy is targeted within a narrow therapeutic blood concentration range, and management of patients on lithium typically involves regular blood tests to ensure therapeutic steady-state plasma-level circulating doses that do not risk lithium toxicity (23). In a cross-sectional study of UK primary care data that adjusted for risk factors for CKD, Iwagami et al. (14) reported a 6.5-fold higher prevalence of CKD for individuals with severe mental illness and a history of lithium treatment compared with a 1.5-fold higher prevalence for patients with severe mental illness who had no history of lithium treatment. Furthermore, a retrospective longitudinal study found that despite the prevalence of CKD among people without severe mental illness decreasing over a 3-year period, the prevalence of CKD for people with severe mental illness increased (5). Similarly, another longitudinal study described a 1.25-fold higher risk of CKD in people with schizophrenia after diagnosis, within a 3-year follow-up (15).

Kidney Failure and Severe Mental Illness

The relationship between severe mental illness and kidney failure prevalence is poorly understood due to the lack of clarity regarding care pathways for people who have severe mental illness, and the high levels of morbidity and mortality in this patient group. Conversely, mental health conditions are highly prevalent among people who are receiving dialysis, particularly major depressive disorder and anxiety disorders (25). There is also a lack of published data regarding rates of severe mental illness in individuals with CKD. A study by Kimmel et al. (25) demonstrated that 1% of individuals with kidney failure registered with Medicare aged between 22 and 64 years were hospitalized with a primary psychiatric diagnosis of schizophrenia. However, as these data rely solely on inpatient psychiatric hospitalizations, the prevalence of severe mental illness in individuals with CKD and kidney failure is largely unknown.

Health Care Utilization in People with Severe Mental Illness and CKD

Several studies have consistently shown that individuals with CKD and a previous diagnosis of severe mental illness have worse health outcomes, including higher rates of nonpsychiatric hospitalizations, particularly through the emergency department, and longer hospital stays (26,27). The most common reasons for rehospitalization seem to be the same for those with CKD but without severe mental illness, namely heart failure, ischemic heart disease, AKI/acute kidney failure, sepsis, and pneumonia (27). Furthermore, a study by Kimmel et al. (25) showed that hospitalizations of people with psychiatric diagnoses within a year of initiation of KRT were associated with higher mortality after controlling for sociodemographic characteristics and comorbidities.

Kidney Replacement in People with Severe Mental Illness and Kidney Failure

Several studies show that the distribution of KRT modality differs substantially between individuals with and without severe mental illness (13,14,28). For example, in the United Kingdom, individuals with a previous severe mental illness diagnosis were twice as likely to receive hemodialysis but were less likely to receive peritoneal dialysis or a kidney transplant (14). A nationwide population-based cohort study in Israel demonstrated that individuals with kidney failure and schizophrenia were less likely to receive either dialysis or kidney transplantation, despite the health policy in Israel mandating that every patient should have access to dialysis (13). Furthermore, a nationwide cohort study based in China found that individuals with schizophrenia had a 40% lower rate of dialysis but a 23% higher risk of death (28). This study also showed that patients on dialysis with schizophrenia received suboptimal predialysis nephrology care, including fewer appointments with nephrologists and fewer erythropoietin prescriptions; after individuals with schizophrenia became dependent on dialysis, they had an 84% higher risk of death and hospital admission (28). Overall, this suggests that people who have CKD and severe mental illness may not be receiving adequate treatment or support to prevent the development, progression, and complications of CKD and kidney failure. Although previous research has suggested that people who have severe mental illness receive closer monitoring (14) and that this accounts for the higher prevalence of CKD, this interpretation does not account for the poorer clinical outcomes of people who have severe mental illness and CKD. Understanding these outcome disparities remains a priority.

Kidney transplantation can be life changing and is the treatment of choice for individuals with kidney failure (29). Patients with severe mental illness have previously been excluded from transplant programs due to concerns regarding adherence to post-transplant treatment, cognitive and emotional capability, potential drug interactions between immunosuppressant and psychotropic medications, relapse of psychiatric symptoms, and inadequate social support. Indeed, the presence of a severe mental illness has been considered a relative or even absolute contraindication by some (30,31). However, there are few data to support these concerns. Indeed, a number of studies indicate that, after going through a careful selection process, those with and without severe mental illness have similar risk of all-cause death, graft loss, rejection, and frequency of acute rejection episodes (32⇓⇓–35). A study by Butler et al. (35) reported that one patient with bipolar disorder had a brief episode of manic psychosis 2 days post-transplant. This was settled within 3 days by actively involving the liaison psychiatry team and introducing haloperidol and a small reduction in the steroid dose. Similarly, a case study of a person with schizophrenia undergoing transplant described nonadherence issues, which were linked with the person’s wish to recommence dialysis as the person missed the associated social interaction. These adherence issues were successfully managed by finding more appropriate ways to meet the individual’s psychosocial needs (36). Taken together, results indicate that although consideration of severe mental illness is important for pretransplant assessment and selection, there is little evidence that having a diagnosis of severe mental illness negatively affects transplant outcomes.

Challenges in Care Provision for People with CKD and Severe Mental Illness

Qualitative research in the area of CKD and severe mental illness is extremely limited; however, a recent study by Alwar and Addis (37) explored the experiences of nephrology nurses providing care to individuals with severe mental illness receiving acute hemodialysis. Their findings indicate that, although they provide person-centered care, nephrology nurses experience several challenges when providing care to individuals with severe mental illness. Nurses described how the disruptive, unpredictable, and aggressive behaviors sometimes exhibited by some individuals with severe mental illness made them feel vulnerable and, in some cases, unsafe. Lack of education about severe mental illness as well as staff shortages were identified as significantly affecting care delivery, whereas effective communication, empathy, and close collaboration with the psychiatric liaison team were identified as key facilitators of effective care. Although research is limited, we have outlined in Table 1 several recommendations for providing care to individuals with CKD and severe mental illness on the basis of our own experience with this patient group.

In conclusion, individuals with severe mental illness are at a higher risk of developing CKD. There is a greater burden of known risk factors among patients with severe mental illness; however, this does not fully explain the higher proportion of CKD in this population, and improved understanding of factors influencing disease onset and progression is urgently needed.

Furthermore, for individuals with CKD, having severe mental illness is associated with poor health outcomes and suboptimal kidney care. As health care disparities for individuals with CKD and co-occurring severe mental illness are multidimensional, close multidisciplinary collaboration is needed to improve health care access and health outcomes for this population. Limited research suggests that care might be improved through educating nephrology health care staff regarding the needs of individuals with severe mental illness and by facilitating closer collaboration with psychiatry. Further research investigating the rates of severe mental illness in individuals with CKD, as well as the barriers and facilitators to effective care for this population, is clearly required to inform the provision of appropriate supports and to improve health outcomes for individuals with CKD and co-occurring severe mental illness.

Disclosures

K. Bramham reports consultancy agreements with Alexion, AstraZeneca, and Perkin Elmer; research funding from Alexion and AstraZeneca; honoraria from Alexion, AstraZeneca, and Otsuka; and serving in an advisory or leadership role with Alexion and AstraZeneca. C. Carswell is on the European Dialysis and Transplace Nurses Association/ European Renal Care Association scientific board; received research support funding previously from Kidney Care UK and the Northern Ireland Kidney Patient Association; and is currently working on two funded research programs: one by National Institutes of Health Research and one by Marie Curie Research. In both instances, C. Carswell is not the grant holder and is not named on the funding application. All remaining authors have nothing to disclose.

Funding

None.

Author Contributions

C. Cogley conceptualized the study; C. Carswell and C. Cogley were responsible for investigation; K. Bramham and J. Chilcot provided supervision; C. Carswell and C. Cogley wrote the original draft; and K. Bramham, C. Carswell, J. Chilcot, and C. Cogley reviewed and edited the manuscript.