Chronic kidney disease (CKD) is a major health concern and like many chronic illnesses is invariably associated with various psychiatric conditions and poorer quality of life. CKD negatively affects patients’ social, financial, and psychological well-being. (1,2) Patients with CKD are thought to be highly susceptible to emotional problems because of the chronic stress related to disease burden, dietary restrictions, functional limitations, associated chronic illness and comorbidities, adverse effects of medication, changes in self-perception and fear of death. Hemodialysis patients have lower quality of life, more functional impairments, greater occurrence of psychopathological states including suicidal ideation, lower adherence to drug treatment and an increased likelihood of long term body-pain.(3) Psychiatric Co morbidity in CKD patients can interfere with wellbeing and productivity, ability to concentrate and process information, or the ability to make decisions and participate meaningfully in self-care. Therefore, the diagnosis and treatment of these conditions becomes important to improve psychological and overall well-being, quality of life and consequently, reduce morbidity and mortality risk in this population.

Overall, depression is the most common psychiatric/psychological problem (likely together with anxiety). The estimated prevalence of depressive disorders is 13-22% in primary care clinics but is only recognized in approximately 50% of cases.[4]. These figures seem to largely underestimate actual prevalence owing to the scarcity of data obtained using psychiatric diagnostic criteria and lack of large, well-designed epidemiological research studies in patients with end-stage renal disease (ESRD). Another diagnostic challenge is the significant overlap in symptomatology between depression and anxiety disorders, and the fact that these two conditions often simultaneously coexist in the general population as well as  in HD patients (5,6). Anxiety in CKD patients often coexists with depression and even seems to aggravate the depressive symptoms interfering with wellbeing and productivity, the ability to concentrate and process information, or the ability to make decisions and participate meaningfully in self-care. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear (5). It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. Therefore, as is the case with depression in ESRD patients, complete evaluation to exclude these disorders as part of the uremia, and not a psychiatric disorder, is necessary. The major challenge in definitive diagnosis is due to a potential overlap of symptoms of the psychological disorder with complications of uremia. For example, Fatigue may be related to diverse organ system disorders in ESRD, such as anemia or myopathies and may be somatisation of underlying depression. Similarly, cognitive dysfunction may reflect uremic encephalopathy or the psychiatric illness (7). Both depression and anxiety are found to be predictors of morbidity and mortality in dialysis patients and are responsible for compromising treatment compliance and downgrading their immune and nutritional status.

Decreased quality of sleep is common in dialysis patients and is associated with decreased health-related quality of life. (8) The causes of poor sleep in CKD patients include anxiety, depression, fatigue, restless leg syndrome, obstructive sleep apnea etc. The reported prevalence of ‘poor sleep’ in dialysis patients is in the range of 45–80%. (9). Although some studies on depression, anxiety and sleep quality have been conducted, the majority of the studies conducted are from the western countries. Research findings on these mental health related issues in Indian CKD population is scarce.

REVIEW METHODOLOGY-

Electronic searches were conducted using title and subject headings for ‘psychiatric ‘/ ‘psychological ‘, ‘depression’, ‘mood disorders’, ‘depressive disorder’, ‘mental health’, ‘mental illness’ in combination with ‘kidney disease’, ‘renal dialysis’, renal insufficiency’ and ‘kidney failure’.

Though not briefing the clinical management guidelines as such, this review aims to summarise the evidence regarding pyschiatrc Co morbidity in CKD in order to aid clinical decision.

EPIDEMIOLOGY-

With the use of a clinician-administered semistructured interview in the study by Cukor d et al in 2007 in 70 randomly selected patient’s mainly black patients, more than 70% were diagnosed with Psychiatric illness. Out of these 29 % were diagnosed with depressive disorder (20% had major depression, and 9% had a diagnosis of dysthymia or depression cannot be categorised) and 27% with major anxiety disorder(29). In these patient’s 10% had a psychotic disorder and 9% had history of substance abuse.A total of 7.1% were also diagnosed as other psychiatric illness or compound depressive disorder.(10)Further in the study it is observed that  Only 13% patients were seeking  treatment from a  mental health provider, and only 5% reported being prescribed psychiatric medication by their physician.A study(1996-2013)by Kimmel PL et al in 2019  observed that Only  2% of adults and 1% of children were hospitalized with a primary psychiatric diagnosis. In these patient’s, most common primary psychiatric diagnoses were neuropsychiatric illness like organic disorders/dementias in elderly adults and depression/affective disorder in adults and children, and Prevalence of hospitalizations with psychiatric illness increased over time across these groups, mainly from secondary diagnosis :19% of elderly adults, 25% of adults and 15% of children(11).Study by Shirazian S ( 2017) the prevalence of interview-based depression is approximately 20% in both no dialysis and dialysis groups.(12)In India study by H. K. Aggarwal et al (2017) showed prevalence of psychiatric Co morbidity in CKD patient on hemodialysis between 58%-79%.(13)

Why is psychological illness more common in CKD?

There are dynamic and multifactorial complex interactions between depression and CKD patients. Along with the disease, socioeconomic status and childhood diversity play a significant role as most important risk factors for depression (13). Socioeconomic adversity in these patients is associated with high risk  health behaviors such as smoking, poor diet, sedentary lifestyle, as well as delayed help-seeking. These factors increase the risk as well as impair the management of cardiovascular disease, diabetes and dépression (14). There are other biological elements that can be considered to be both part of the shared upstream risk factors, as well as consequences of CKD and depression. Biological elements like inflammatory system, immune system, hypothalamo - pitutary axis disturbance, changes in the parasympathetic and sympathetic nervous systems are being considered to play important role (15).

Out of these important biological elements, inflammation has been suggested as culprit in the bidirectional link between CKD and depression. As evidence for this hypothesis, the higher concentration of pro-inflammatory cytokines has been observed among patients of CKD with symptoms of depression though there is a considerable heterogeneity between the results of various studies (16). Evidence also suggests that these pro-inflammatory cytokines interact with many of the pathophysiological mechanisms of depression, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity and behaviour (16).

In the early stages of CKD, Patients of CKD in their early stage of diagnosis may feel apathetic and losses relating to lifestyle and independence. But the other things also to be considered in these patients are loss of identity and primary role function. Being dependent on treatment for life, patients on dialysis often dislike, or have ambivalent feelings towards the treatment with fear of loss of control on life and freedom. Additionally, these factors may contribute to having feeling of guilt for the burden they perceive, they cause for family members and careers.

Why does psychological Co morbidity in CKD matter?

Although outcomes are slowly improving for patients with ESKD receiving maintenance dialysis, they continue to be notable for exceptionally high rates of hospitalization, morbidity and mortality. In the pursuit of ways to improve these dismal outcomes, substantial attention has historically been paid to cardiovascular disease risk factor reduction, whereas only more recently has the role of psychiatric illness come into focus. Accumulating evidence has shown that clinical depression and subthreshold depressive symptoms are associated with an increased risk for adverse clinical outcomes in patients with CKD. These negative outcomes include increased mortality and rates of hospitalisation, poor adherence to treatment and decreased QOL.

1.Mortality-

The relationship between CKD and survival has been somewhat controversial. Many studies in the past have failed to demonstrate strong relationship between mortality and psychiatric illness. This may be due to the small size and methodological limitations (17). Nonetheless, The Cochrane Renal Group published a systematic review and meta-analysis that helped us to clarify this issue of depression and mortality in CKD. The analysis included 22 cohort studies (83,381 participants) of depressed adults with CKD. Overall, a strong and statistically significant association was found between depression status and risk of all-cause mortality (RR 1.59; 95% CI: 1.35–1.87). These results remained consistent across stages of CKD, regardless of sex or age. (18) Furthermore, the excess mortality risk attributed to depression in CKD was higher than that seen in other chronically diseased populations, such as cancer, diabetes and heart disease (18). Yet, another study by Kimmel PL et al showed that after controlling for potential confounding factors such as sociodemographic variables and general medical comorbidities, found that all-cause mortality was nearly 30 percent greater in patients with psychiatric disorders than controls (hazard ratio 1.29, 95% CI 1.26-1.32) (11).

 2.Hospitalisation-

Multiple studies have shown that depression is associated with increased healthcare costs, including primary, pharmacy, inpatient medical, inpatient psychiatric and outpatient mental health care (19). Comorbid psychiatric disorders in patients on maintenance dialysis are also associated with significant morbidity (20). In a retrospective study that examined patients who were initiated on dialysis and were followed during the first year of dialysis, the primary findings were as following (22): Among patients of age 22 to 64 years (n = approximately 400,000), hospitalization with a primary or secondary psychiatric diagnosis occurred in 2 and 25 percent. Among patients age ≥65 years (n >600,000), hospitalization with a primary or secondary psychiatric diagnosis occurred in 2 and 19 percent. Among patients initiated on dialysis, mortality was greater in those who developed psychiatric illnesses (20) Another retrospective study that used a national registry dedicated to chronic kidney disease and ESKD to identify patients who were hospitalized within the first year of starting dialysis, either with a psychiatric diagnosis (n >11,000) or a nonpsychiatric diagnosis (controls, n >300,000) (11). The most common psychiatric disorders leading to hospitalization included depression, neurocognitive disorders, and substance-related and addictive disorders, and the mean duration of follow-up was approximately three years.

3.Adherence-

 In ESKD psychiatric illness may lead to poor adherence with dialysis and disruptive behavior on dialysis units (20). As an example, depressive symptoms are found to be independently associated with missed hemodialysis treatments, as well as abbreviated treatments that are shortened by the request of patients(21).

Measuring adherence in ESKD patients is particularly challenging. However, most studies have indicated a relationship between depressive affect and both laboratory and behavioral markers of poor compliance in the dialysis patient (22). Depressive symptoms of low motivation, impaired concentration, memory, and apathy can significantly interfere with patients’ adherence to complex and challenging treatment plans. This is important, as decreased behavioral adherence (skipping dialysis sessions, shortening dialysis time) has been shown to be associated with decreased survival (17)

Adherence to a dietary prescription is a particular area of importance as nutritional status has been shown to significantly impact the course and outcome of ESKD. Depression is associated with impaired nutrition in dialysis patients with non-adherence rates to prescribed diet and fluid restriction recommendations of approximately 60.2% (23). Importantly, anti-depressant therapy in conjunction with supportive psychotherapy appears to improve nutritional status in depressed individuals with CKD (23).

 4.Quality of life-

It is now widely accepted that health-related quality of life (HRQOL) is significantly compromised in patients with ESKD  (24). In addition to this higher symptom burden, ESKD patients with depression also experience more fatigue, cognitive difficulties, pain, sleep disturbances, sexual dysfunction and relationship difficulties (25). Furthermore, HRQOL has been associated with increased morbidity and mortality. Depression has been found to have a profound negative impact on HRQOL in CKD patients (13). Additionally, it has been proposed that depression and anxiety may be more strongly associated with HRQOL in CKD than clinical and socio-demographic variables taken together (13). Depression can impact on HRQOL in a number of ways. Patients with depression have been found to have two to threefold more medical symptoms compared with controls without depression (19). Apart from increased levels of symptoms, depression is also linked with reduced functional performance and increased rates of occupational disability (14), often leading to financial strain and reduced well-being.

HRQOL is important in and of itself. However, as both HRQOL and depression are related to survival in dialysis patients (13), this negative association has a clear clinical importance. Recent study by Kim et al in 2019 (n=125) suggested that the mean score of HRQOL was 49.08 ± 11.09, with 48.0 % (95 % CI: 42.2 − 54.5 %) of them having lower HRQOL. Unemployed patients (aOR = 2.40, 95 % CI: 1.10–5.90) and patients who had hemodialysis 2 times per week (aOR = 1.71, 95 % CI: 1.07–3.83) had lower HRQOL. Elderly patients had higher odds of having lower mean score on the burden of kidney disease (aOR = 2.07; 95 % CI 1.18–4.13) as compared to the younger patients. (25)

Diagnosis and treatment — 

Among patients who are treated with maintenance dialysis, the diagnostic criteria for psychiatric disorders are identical to those used in the general population (26). Psychiatric disorders in patients receiving maintenance dialysis are often underdiagnosed (20). One reason may be that symptoms of psychiatric disorders overlap with symptoms of inadequate dialysis, complications of ESKD, and medication adverse effects (27). In addition, psychiatric illnesses in patients with ESKD are undertreated and relatively few studies have examined how to treat comorbid mental disorders (20). Thus, the efficacy of therapeutic interventions for psychiatric conditions is often not clear, and treatment recommendations are generally based upon patients in the general population of patients with psychiatric disorders. The combination of pharmacotherapy and psychotherapy is likely to be successful and may be cost effective (30). Most patients are referred to psychiatrists and other mental health clinicians if these specialists are available and major indication include suicidal ideation, functional impairment or fluctuating symptoms etc.(28)For patients treated with maintenance dialysis, the dose of most psychotropic medications does not need to be adjusted because they are metabolized in the liver (6). However, the metabolites are often excreted by the kidney and a minority of drugs may require a dose adjustment. Dosing recommendations that are specific for hemodialysis and peritoneal dialysis can be found in the Lexicomp drug information topic for that drug, in the section on dosing in renal impairment. Some of the dose recommendations are based upon the European Renal Best Practice guideline (31).

This literature review has been conducted in an attempt to explore the main psychosocial factors in people with CKD of varying severities and those on undergoing hemodialysis. Depression, anxiety, stress are common conditions among chronic kidney disease patients and that they occur more frequently among CKD and those undergoing dialysis. Lower quality-of-life scores are also associated with symptoms of psychiatric co-morbidities. Presence of comorbidities, loss of vascular access and worse quality of life were associated with anxiety symptoms among   dialysis patients. Timely and appropriate interventions lead to recovery of psychiatric problems Which eventually improve Quality of life and life expectancy.

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