Quality of Life and Depression in CKD: Improving Hope and Health

Abstract

Related Articles, pp. 424 and 433Life on dialysis is difficult. Dialysis patients are burdened with a part-time job they never applied for and cannot quit unless they undergo transplantation or withdraw from care. Their income from this “profession” is nil at best. In comparison to healthier counterparts, they carry a 5- to 500-fold greater risk of death, cannot eat what they please, can take pleasure trips only with extensive advanced planning, have a poor sex life, and must work all major holidays except Thanksgiving and Christmas.1Parfrey P.S. Foley R.N. The clinical epidemiology of cardiac disease in chronic renal failure.J Am Soc Nephrol. 1999; 10: 1606-1615PubMed Google Scholar, 2Palmer B.F. Sexual dysfunction in uremia.J Am Soc Nephrol. 1999; 10: 1381-1388PubMed Google Scholar It is no wonder that the quality of life on dialysis therapy is poor and depression rates are high.3Kimmel P.L. Psychosocial factors in dialysis patients.Kidney Int. 2001; 59: 1599-1613Crossref PubMed Scopus (276) Google Scholar, 4Perlman R.L. Finkelstein F.O. Liu L. et al.Quality of life in chronic kidney disease (CKD): A cross-sectional analysis in the Renal Research Institute-CKD study.Am J Kidney Dis. 2005; 45: 658-666Abstract Full Text Full Text PDF PubMed Scopus (307) Google ScholarIn comparison, one might hypothesize a much brighter outlook for patients with chronic kidney disease (CKD) who are not burdened with the job of dialysis therapy. However, they also are treated to colorless diets, complementary comorbid conditions, curtailed life spans, and clear socioeconomic disadvantage versus the general population.5Go A.S. Chertow G.M. Fan D. McCulloch C.E. Hsu C.Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.N Engl J Med. 2004; 351: 1296-1305Crossref PubMed Scopus (8839) Google Scholar, 6White S.L. McGeechan K. Jones M. et al.Socioeconomic disadvantage and kidney disease in the United States, Australia, and Thailand.Am J Public Health. 2008; 98: 1306-1313Crossref PubMed Scopus (39) Google Scholar Previously unaware of their relatively silent affliction, many are surprised to find that their kidney function is less than half of what is considered normal. Nonetheless, these patients have not been well known to experience high rates of depression or lack of quality in their lives because few descriptive data previously existed.In this issue of the American Journal of Kidney Diseases, Hedayati et al7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar offer new insights in the area of depression, a major component in quality-of-life assessment, in non–dialysis-dependent patients with CKD. The article beginning on page 433 validates simple instruments to assess depression in veterans with CKD against gold-standard tools.7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar The article beginning on page 424 determines the prevalence of major depression in patients with CKD and describes factors associated with major depression in this population.8Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Prevalence of major depressive episode in CKD.Am J Kidney Dis. 2009; 54: 424-432Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar Thus, these articles establish trunks from which fruitful branches of further understanding can grow.Interestingly, the first known medical use of the term “quality of life” originated in a 1966 article about patients on maintenance dialysis therapy. The procedure was life saving, but the investigators questioned whether the patient's quality of life was acceptable.9Retan J.W. Lewis H.Y. Repeated dialysis of indigent patients for chronic renal failure.Ann Intern Med. 1966; 64: 284-292Crossref PubMed Scopus (22) Google Scholar, 10Prutkin J.M. Feinstein A.R. Quality-of-life measurements: Origin and pathogenesis.Yale J Biol Med. 2002; 75: 79-93PubMed Google Scholar The accompanying editorial mentioned that quality of life is difficult to define. They borrow Sir Francis Bacon's definition, which is “the harmony within a man, and between a man and world”11Elkinton J.R. Medicine and the quality of life.Ann Intern Med. 1966; 64: 711-714Crossref PubMed Scopus (86) Google Scholar; the quantification of such harmony poses measurement difficulties.10Prutkin J.M. Feinstein A.R. Quality-of-life measurements: Origin and pathogenesis.Yale J Biol Med. 2002; 75: 79-93PubMed Google Scholar More than 40 years later, our profession still struggles with the challenges created when trying to generate hypotheses regarding quality of life and depression as a cause or result of an intervention. Even the current definition of health-related quality of life put forth by the World Health Organization (“A complete state of physical, mental, and social well-being and not merely the absence of disease and infirmity”12Sloan J.A. Cella D. Frost M. Guyatt G.H. Sprangers M. Symonds T. Assessing clinical significance in measuring oncology patient quality of life: Introduction to the symposium, content overview, and definition of terms.Mayo Clin Proc. 2002; 77: 367-370Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar) is difficult to translate into readily measured entities (ie, metrics of depression).Tools to assess factors impacting on corollaries of quality of life, such as depression, have since been used and validated, primarily in dialysis patients. Early assessments in the late 1960s and early 1970s showed rates of depression of 0% to 100%, questioning the true validity of the instruments available at the time.3Kimmel P.L. Psychosocial factors in dialysis patients.Kidney Int. 2001; 59: 1599-1613Crossref PubMed Scopus (276) Google Scholar, 13Wright R.G. Sand P. Livingston G. Psychological stress during hemodialysis for chronic renal failure.Ann Intern Med. 1966; 64: 611-621Crossref PubMed Scopus (70) Google Scholar, 14Glassman B.M. Siegel A. Personality correlates of survival in a long-term hemodialysis program.Arch Gen Psychiatry. 1970; 22: 566-574Crossref PubMed Scopus (31) Google Scholar, 15Reichsman F. Levy N.B. Problems in adaptation to maintenance hemodialysis A four-year study of 25 patients.Arch Intern Med. 1972; 130: 859-865Crossref PubMed Scopus (92) Google Scholar Since then, many other instruments have been used. Rates of depressive disorder are as high as 26% to 29% in recent cohorts of patients with CKD, with rates of major depressive disorder ranging from 17% to 19% in comparison to 4% to 6% in the general and 6% to 10% in primary care clinic populations.7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 16Watnick S. Wang P.L. Demadura T. Ganzini L. Validation of 2 depression screening tools in dialysis patients.Am J Kidney Dis. 2005; 46: 919-924Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar Major depression is defined as lasting for 2 weeks or more, during which time patients experience anhedonia or depressed mood and at least 5 of the 9 Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria symptom domains, which include weight loss, sleep disturbances, psychomotor abnormalities, fatigue, feelings of worthlessness or guilt, inability to concentrate, and thoughts of death. These symptoms are not supposed to be attributable to a general medical condition, which makes the diagnosis very difficult in patients with CKD.17First M.B. Donovan S. Frances A. Nosology of chronic mood disorders.Psychiatr Clin North Am. 1996; 19: 29-39Abstract Full Text Full Text PDF PubMed Scopus (42) Google ScholarNot everyone with CKD is depressed; thus, robust screening tools are essential to focus resources. Hedayati's group validates 2 of these screening tools against gold-standard criteria in the nondialysis CKD population: the Quick Inventory of Depressive Symptomatology and Self-Report (QIDS-SR16) and Beck Depression Inventory (BDI).18Rush A.J. Trivedi M.H. Ibrahim H.M. et al.The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression.Biol Psychiatry. 2003; 54: 573-583Abstract Full Text Full Text PDF PubMed Scopus (2479) Google Scholar, 19Beck A.T. Steer R.A. Carbin M.G. Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation.Clin Psychol Rev. 1988; 8: 77-100Crossref Scopus (9094) Google Scholar The Patient Health Questionnaire, which has been validated in dialysis patients, also has been used in patients with non–dialysis-dependent CKD16Watnick S. Wang P.L. Demadura T. Ganzini L. Validation of 2 depression screening tools in dialysis patients.Am J Kidney Dis. 2005; 46: 919-924Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar, 20Abdel-Kader K. Unruh M.L. Weisbord S.D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease.Clin J Am Soc Nephrol. 2009; 4: 1057-1064Crossref PubMed Scopus (305) Google Scholar (Box 1, Box 2). Using the QIDS-SR16 and BDI alongside gold-standard assessments for depression, Hedayati et al7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar report the incidence of major depressive disorder to be 21% in this population, although there was no control group. Others looking at rates of depressive symptoms in the CKD population have shown rates similar to either a general medical population22Cohen S.D. Patel S.S. Khetpal P. Peterson R.A. Kimmel P.L. Pain, sleep disturbance, and quality of life in patients with chronic kidney disease.Clin J Am Soc Nephrol. 2007; 2: 919-925Crossref PubMed Scopus (111) Google Scholar or dialysis patients in their systems; however, gold-standard evaluations of depression were not included.20Abdel-Kader K. Unruh M.L. Weisbord S.D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease.Clin J Am Soc Nephrol. 2009; 4: 1057-1064Crossref PubMed Scopus (305) Google Scholar Given this limitation, the relative contribution of nondialysis CKD to the diagnosis of major depression previously was unclear. The use of gold-standard assessments identified the relatively high prevalence of depression in Dr Hedayati's target population; this moves the field forward by validating short easily administered instruments to assess depressive symptoms.Components of the Quick Inventory of Depressive Symptomatology (Self Report)1Falling asleep2Sleeping during the night3Waking up too early4Sleeping too much5Feeling sad6Decreased appetite7Increased appetite8Decreased weight9Increased weight10Concentration/decision making11View of self12Thoughts of death or suicide13General interest14Energy level15Feeling slowed down16Feeling restlessNote: The 16 questions are self-reported on a scale of 0 to 3 based on the past 7 days, with higher scores indicating greater severity of symptoms.Reproduced with permission.18Rush A.J. Trivedi M.H. Ibrahim H.M. et al.The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression.Biol Psychiatry. 2003; 54: 573-583Abstract Full Text Full Text PDF PubMed Scopus (2479) Google ScholarComponents of the Patient Health Questionnaire1Little interest or pleasure in doing things2Feeling down, depressed, or hopeless3Trouble falling or staying asleep or sleeping too much4Feeling tired or having little energy5Poor appetite or overeating6Feeling bad about yourself7Trouble concentrating on things8Moving or speaking slowly or the opposite (restless or fidgety)9Thoughts that you would be better off dead or of hurting yourselfNote: The 9 questions can be self-administered on a scale of 0 to 3 based on the past 2 weeks, with higher scores indicating greater severity of symptoms.Reproduced with permission.21Spitzer R.L. Kroenke K. Williams J.B. Validation and utility of a self-report version of PRIME-MD: The PHQ primary care study Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire.JAMA. 1999; 282: 1737-1744Crossref PubMed Scopus (6628) Google ScholarDepression in the CKD population is tightly correlated with poor quality of life,22Cohen S.D. Patel S.S. Khetpal P. Peterson R.A. Kimmel P.L. Pain, sleep disturbance, and quality of life in patients with chronic kidney disease.Clin J Am Soc Nephrol. 2007; 2: 919-925Crossref PubMed Scopus (111) Google Scholar, 23Abdel-Kader K. Myaskovsky L. Karpov I. et al.Individual quality of life in chronic kidney disease: Influence of age and dialysis modality.Clin J Am Soc Nephrol. 2009; 4: 711-718Crossref PubMed Scopus (61) Google Scholar and it is an independent risk factor for a greater rate of illness and death in dialysis patients. However, research in the nondialysis CKD population, including the articles by Hedayati et al,7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 8Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Prevalence of major depressive episode in CKD.Am J Kidney Dis. 2009; 54: 424-432Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar is not longitudinally based and therefore is unable to draw such conclusions. Nonetheless, the article in this issue of AJKD shows that an association exists between depression and factors that may lead to poor outcomes, including diabetes, prior psychiatric illness, drug and alcohol use, and use of antidepressant medications.8Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Prevalence of major depressive episode in CKD.Am J Kidney Dis. 2009; 54: 424-432Abstract Full Text Full Text PDF PubMed Scopus (132) Google ScholarThe biological rationale for poor outcomes with depressive symptoms is unclear. Depression results in abnormal hypothalamic-pituitary axis activity, with increased norepinephrine and cortisol secretion, which may have adverse consequences in a population with exorbitant rates of cardiovascular disease.24Otte C. Neylan T.C. Pipkin S.S. Browner W.S. Whooley M.A. Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with coronary disease: Findings from the Heart and Soul Study.Am J Psychiatry. 2005; 162: 2139-2145Crossref PubMed Scopus (86) Google Scholar Altered autonomic tone has been found in depressed patients after myocardial infarction.25Krittayaphong R. Cascio W.E. Light K.C. et al.Heart rate variability in patients with coronary artery disease: Differences in patients with higher and lower depression scores.Psychosom Med. 1997; 59: 231-235PubMed Google Scholar Additional abnormalities in serotonin levels lead to upregulation of platelet activation, with further potential for adverse cardiac events. The uremic milieu may cause a unique biological perturbation in patients with depression, with possible synergistic cardiac abnormalities. Uremia also may make patients more susceptible to mood disorders, but this is conjecture. The additional stressors faced by patients with CKD may both lead to depressive symptoms and hinder medical compliance, leading to worse care and outcomes.26Kimmel P.L. Cohen S.D. Peterson R.A. Depression in patients with chronic renal disease: Where are we going?.J Ren Nutr. 2008; 18: 99-103Abstract Full Text Full Text PDF PubMed Scopus (39) Google ScholarResearch translating into improved care surrounding quality of life and depression is minimal, in part because of a paucity of outcome data for baseline issues.27Thombs B.D. Bassel M. Jewett L.R. Analyzing effectiveness of long-term psychodynamic psychotherapy.JAMA. 2009; 301 (author reply, 932-933): 930Crossref PubMed Scopus (15) Google Scholar How this information translates to the 26 million non–dialysis-dependent patients with CKD in this country is unclear.28Levey A.S. Coresh J. Balk E. et al.National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification.Ann Intern Med. 2003; 139: 137-147Crossref PubMed Scopus (3626) Google Scholar Improvement in care is unlikely to occur until an entity is recognized, studied, and treated. In 1 group of patients initiating dialysis therapy with BDI scores of 15 or higher, only 16% were receiving therapy.29Watnick S. Kirwin P. Mahnensmith R. Concato J. The prevalence and treatment of depression among patients starting dialysis.Am J Kidney Dis. 2003; 41: 105-110Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar In another group of dialysis patients, only half those offered treatment for depression accepted it.30Wuerth D. Finkelstein S.H. Ciarcia J. Peterson R. Kliger A.S. Finkelstein F.O. Identification and treatment of depression in a cohort of patients maintained on chronic peritoneal dialysis.Am J Kidney Dis. 2001; 37: 1011-1017Abstract Full Text PDF PubMed Scopus (113) Google Scholar In prior large randomized controlled trials, such as the Sertaline Antidepressant Heart Attack Randomized Trial (SADHART), patients with kidney disease were excluded.31Glassman A.H. O'Connor C.M. Califf R.M. et al.Sertraline treatment of major depression in patients with acute MI or unstable angina.JAMA. 2002; 288: 701-709Crossref PubMed Scopus (1231) Google Scholar Because our patients rarely are included in adequate trials of antidepressant therapy, we do not know the efficacy of treatment. Antidepressant trials of dialysis patients have had small sample sizes, lack of control groups, and inadequate follow-up. Side effects can compound symptoms and signs that our patients already experience. Central nervous system depression, increased bleeding risks, worsening nausea, sexual dysfunction, electrocardiogram abnormalities, and accumulation of toxic metabolites could be described in a brochure about either antidepressant side effects or advanced CKD. Other therapies, such as exercise and cognitive behavioral intervention, suggest a minimal positive effect.32Painter P. Physical functioning in end-stage renal disease patients: Update 2005.Hemodial Int. 2005; 9: 218-235Crossref PubMed Scopus (185) Google Scholar, 33Cukor D. Use of CBT to treat depression among patients on hemodialysis.Psychiatr Serv. 2007; 58: 711-712Crossref PubMed Scopus (30) Google Scholar Sadly, as we wonder about improvement in outcomes after therapy for depression in patients with CKD, we remain blinded.The state of affairs regarding care for these patients, simply put, is depressing. Extensive guidelines have been established addressing many of the numbers that go awry for our patients with CKD. However, when a patient walks through the door of the dialysis unit or a provider's office, the patient's first thought is not whether he or she has met Kidney Disease Outcomes Quality Initiative guidelines. A first thought might be: How will I feel today? How is this impacting my life? This reminds us to consider such issues as depression and quality of life alongside the traditional guidelines. Our goal is the betterment of the lives of our patients, and depression as it impacts on quality of life clearly is a field that requires further exploration. Future studies must assess long-term outcomes in patients with CKD and depression so that we better understand the implication of such a diagnosis. Subsequently, randomized controlled trials need to address the efficacy and tolerability of therapy as it pertains to our patients. The articles by Hedayati et al7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 8Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Prevalence of major depressive episode in CKD.Am J Kidney Dis. 2009; 54: 424-432Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar are a first step toward the day when our patients can not only hope for, but also expect, treatments for their kidney disease that encompass their physical and mental well-being. Related Articles, pp. 424 and 433 Related Articles, pp. 424 and 433 Related Articles, pp. 424 and 433 Life on dialysis is difficult. Dialysis patients are burdened with a part-time job they never applied for and cannot quit unless they undergo transplantation or withdraw from care. Their income from this “profession” is nil at best. In comparison to healthier counterparts, they carry a 5- to 500-fold greater risk of death, cannot eat what they please, can take pleasure trips only with extensive advanced planning, have a poor sex life, and must work all major holidays except Thanksgiving and Christmas.1Parfrey P.S. Foley R.N. The clinical epidemiology of cardiac disease in chronic renal failure.J Am Soc Nephrol. 1999; 10: 1606-1615PubMed Google Scholar, 2Palmer B.F. Sexual dysfunction in uremia.J Am Soc Nephrol. 1999; 10: 1381-1388PubMed Google Scholar It is no wonder that the quality of life on dialysis therapy is poor and depression rates are high.3Kimmel P.L. Psychosocial factors in dialysis patients.Kidney Int. 2001; 59: 1599-1613Crossref PubMed Scopus (276) Google Scholar, 4Perlman R.L. Finkelstein F.O. Liu L. et al.Quality of life in chronic kidney disease (CKD): A cross-sectional analysis in the Renal Research Institute-CKD study.Am J Kidney Dis. 2005; 45: 658-666Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar In comparison, one might hypothesize a much brighter outlook for patients with chronic kidney disease (CKD) who are not burdened with the job of dialysis therapy. However, they also are treated to colorless diets, complementary comorbid conditions, curtailed life spans, and clear socioeconomic disadvantage versus the general population.5Go A.S. Chertow G.M. Fan D. McCulloch C.E. Hsu C.Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.N Engl J Med. 2004; 351: 1296-1305Crossref PubMed Scopus (8839) Google Scholar, 6White S.L. McGeechan K. Jones M. et al.Socioeconomic disadvantage and kidney disease in the United States, Australia, and Thailand.Am J Public Health. 2008; 98: 1306-1313Crossref PubMed Scopus (39) Google Scholar Previously unaware of their relatively silent affliction, many are surprised to find that their kidney function is less than half of what is considered normal. Nonetheless, these patients have not been well known to experience high rates of depression or lack of quality in their lives because few descriptive data previously existed. In this issue of the American Journal of Kidney Diseases, Hedayati et al7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar offer new insights in the area of depression, a major component in quality-of-life assessment, in non–dialysis-dependent patients with CKD. The article beginning on page 433 validates simple instruments to assess depression in veterans with CKD against gold-standard tools.7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar The article beginning on page 424 determines the prevalence of major depression in patients with CKD and describes factors associated with major depression in this population.8Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Prevalence of major depressive episode in CKD.Am J Kidney Dis. 2009; 54: 424-432Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar Thus, these articles establish trunks from which fruitful branches of further understanding can grow. Interestingly, the first known medical use of the term “quality of life” originated in a 1966 article about patients on maintenance dialysis therapy. The procedure was life saving, but the investigators questioned whether the patient's quality of life was acceptable.9Retan J.W. Lewis H.Y. Repeated dialysis of indigent patients for chronic renal failure.Ann Intern Med. 1966; 64: 284-292Crossref PubMed Scopus (22) Google Scholar, 10Prutkin J.M. Feinstein A.R. Quality-of-life measurements: Origin and pathogenesis.Yale J Biol Med. 2002; 75: 79-93PubMed Google Scholar The accompanying editorial mentioned that quality of life is difficult to define. They borrow Sir Francis Bacon's definition, which is “the harmony within a man, and between a man and world”11Elkinton J.R. Medicine and the quality of life.Ann Intern Med. 1966; 64: 711-714Crossref PubMed Scopus (86) Google Scholar; the quantification of such harmony poses measurement difficulties.10Prutkin J.M. Feinstein A.R. Quality-of-life measurements: Origin and pathogenesis.Yale J Biol Med. 2002; 75: 79-93PubMed Google Scholar More than 40 years later, our profession still struggles with the challenges created when trying to generate hypotheses regarding quality of life and depression as a cause or result of an intervention. Even the current definition of health-related quality of life put forth by the World Health Organization (“A complete state of physical, mental, and social well-being and not merely the absence of disease and infirmity”12Sloan J.A. Cella D. Frost M. Guyatt G.H. Sprangers M. Symonds T. Assessing clinical significance in measuring oncology patient quality of life: Introduction to the symposium, content overview, and definition of terms.Mayo Clin Proc. 2002; 77: 367-370Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar) is difficult to translate into readily measured entities (ie, metrics of depression). Tools to assess factors impacting on corollaries of quality of life, such as depression, have since been used and validated, primarily in dialysis patients. Early assessments in the late 1960s and early 1970s showed rates of depression of 0% to 100%, questioning the true validity of the instruments available at the time.3Kimmel P.L. Psychosocial factors in dialysis patients.Kidney Int. 2001; 59: 1599-1613Crossref PubMed Scopus (276) Google Scholar, 13Wright R.G. Sand P. Livingston G. Psychological stress during hemodialysis for chronic renal failure.Ann Intern Med. 1966; 64: 611-621Crossref PubMed Scopus (70) Google Scholar, 14Glassman B.M. Siegel A. Personality correlates of survival in a long-term hemodialysis program.Arch Gen Psychiatry. 1970; 22: 566-574Crossref PubMed Scopus (31) Google Scholar, 15Reichsman F. Levy N.B. Problems in adaptation to maintenance hemodialysis A four-year study of 25 patients.Arch Intern Med. 1972; 130: 859-865Crossref PubMed Scopus (92) Google Scholar Since then, many other instruments have been used. Rates of depressive disorder are as high as 26% to 29% in recent cohorts of patients with CKD, with rates of major depressive disorder ranging from 17% to 19% in comparison to 4% to 6% in the general and 6% to 10% in primary care clinic populations.7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 16Watnick S. Wang P.L. Demadura T. Ganzini L. Validation of 2 depression screening tools in dialysis patients.Am J Kidney Dis. 2005; 46: 919-924Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar Major depression is defined as lasting for 2 weeks or more, during which time patients experience anhedonia or depressed mood and at least 5 of the 9 Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria symptom domains, which include weight loss, sleep disturbances, psychomotor abnormalities, fatigue, feelings of worthlessness or guilt, inability to concentrate, and thoughts of death. These symptoms are not supposed to be attributable to a general medical condition, which makes the diagnosis very difficult in patients with CKD.17First M.B. Donovan S. Frances A. Nosology of chronic mood disorders.Psychiatr Clin North Am. 1996; 19: 29-39Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar Not everyone with CKD is depressed; thus, robust screening tools are essential to focus resources. Hedayati's group validates 2 of these screening tools against gold-standard criteria in the nondialysis CKD population: the Quick Inventory of Depressive Symptomatology and Self-Report (QIDS-SR16) and Beck Depression Inventory (BDI).18Rush A.J. Trivedi M.H. Ibrahim H.M. et al.The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression.Biol Psychiatry. 2003; 54: 573-583Abstract Full Text Full Text PDF PubMed Scopus (2479) Google Scholar, 19Beck A.T. Steer R.A. Carbin M.G. Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation.Clin Psychol Rev. 1988; 8: 77-100Crossref Scopus (9094) Google Scholar The Patient Health Questionnaire, which has been validated in dialysis patients, also has been used in patients with non–dialysis-dependent CKD16Watnick S. Wang P.L. Demadura T. Ganzini L. Validation of 2 depression screening tools in dialysis patients.Am J Kidney Dis. 2005; 46: 919-924Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar, 20Abdel-Kader K. Unruh M.L. Weisbord S.D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease.Clin J Am Soc Nephrol. 2009; 4: 1057-1064Crossref PubMed Scopus (305) Google Scholar (Box 1, Box 2). Using the QIDS-SR16 and BDI alongside gold-standard assessments for depression, Hedayati et al7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar report the incidence of major depressive disorder to be 21% in this population, although there was no control group. Others looking at rates of depressive symptoms in the CKD population have shown rates similar to either a general medical population22Cohen S.D. Patel S.S. Khetpal P. Peterson R.A. Kimmel P.L. Pain, sleep disturbance, and quality of life in patients with chronic kidney disease.Clin J Am Soc Nephrol. 2007; 2: 919-925Crossref PubMed Scopus (111) Google Scholar or dialysis patients in their systems; however, gold-standard evaluations of depression were not included.20Abdel-Kader K. Unruh M.L. Weisbord S.D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease.Clin J Am Soc Nephrol. 2009; 4: 1057-1064Crossref PubMed Scopus (305) Google Scholar Given this limitation, the relative contribution of nondialysis CKD to the diagnosis of major depression previously was unclear. The use of gold-standard assessments identified the relatively high prevalence of depression in Dr Hedayati's target population; this moves the field forward by validating short easily administered instruments to assess depressive symptoms. 1Falling asleep2Sleeping during the night3Waking up too early4Sleeping too much5Feeling sad6Decreased appetite7Increased appetite8Decreased weight9Increased weight10Concentration/decision making11View of self12Thoughts of death or suicide13General interest14Energy level15Feeling slowed down16Feeling restlessNote: The 16 questions are self-reported on a scale of 0 to 3 based on the past 7 days, with higher scores indicating greater severity of symptoms.Reproduced with permission.18Rush A.J. Trivedi M.H. Ibrahim H.M. et al.The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression.Biol Psychiatry. 2003; 54: 573-583Abstract Full Text Full Text PDF PubMed Scopus (2479) Google Scholar 1Falling asleep2Sleeping during the night3Waking up too early4Sleeping too much5Feeling sad6Decreased appetite7Increased appetite8Decreased weight9Increased weight10Concentration/decision making11View of self12Thoughts of death or suicide13General interest14Energy level15Feeling slowed down16Feeling restless Note: The 16 questions are self-reported on a scale of 0 to 3 based on the past 7 days, with higher scores indicating greater severity of symptoms. Reproduced with permission.18Rush A.J. Trivedi M.H. Ibrahim H.M. et al.The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression.Biol Psychiatry. 2003; 54: 573-583Abstract Full Text Full Text PDF PubMed Scopus (2479) Google Scholar 1Little interest or pleasure in doing things2Feeling down, depressed, or hopeless3Trouble falling or staying asleep or sleeping too much4Feeling tired or having little energy5Poor appetite or overeating6Feeling bad about yourself7Trouble concentrating on things8Moving or speaking slowly or the opposite (restless or fidgety)9Thoughts that you would be better off dead or of hurting yourselfNote: The 9 questions can be self-administered on a scale of 0 to 3 based on the past 2 weeks, with higher scores indicating greater severity of symptoms.Reproduced with permission.21Spitzer R.L. Kroenke K. Williams J.B. Validation and utility of a self-report version of PRIME-MD: The PHQ primary care study Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire.JAMA. 1999; 282: 1737-1744Crossref PubMed Scopus (6628) Google Scholar 1Little interest or pleasure in doing things2Feeling down, depressed, or hopeless3Trouble falling or staying asleep or sleeping too much4Feeling tired or having little energy5Poor appetite or overeating6Feeling bad about yourself7Trouble concentrating on things8Moving or speaking slowly or the opposite (restless or fidgety)9Thoughts that you would be better off dead or of hurting yourself Note: The 9 questions can be self-administered on a scale of 0 to 3 based on the past 2 weeks, with higher scores indicating greater severity of symptoms. Reproduced with permission.21Spitzer R.L. Kroenke K. Williams J.B. Validation and utility of a self-report version of PRIME-MD: The PHQ primary care study Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire.JAMA. 1999; 282: 1737-1744Crossref PubMed Scopus (6628) Google Scholar Depression in the CKD population is tightly correlated with poor quality of life,22Cohen S.D. Patel S.S. Khetpal P. Peterson R.A. Kimmel P.L. Pain, sleep disturbance, and quality of life in patients with chronic kidney disease.Clin J Am Soc Nephrol. 2007; 2: 919-925Crossref PubMed Scopus (111) Google Scholar, 23Abdel-Kader K. Myaskovsky L. Karpov I. et al.Individual quality of life in chronic kidney disease: Influence of age and dialysis modality.Clin J Am Soc Nephrol. 2009; 4: 711-718Crossref PubMed Scopus (61) Google Scholar and it is an independent risk factor for a greater rate of illness and death in dialysis patients. However, research in the nondialysis CKD population, including the articles by Hedayati et al,7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 8Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Prevalence of major depressive episode in CKD.Am J Kidney Dis. 2009; 54: 424-432Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar is not longitudinally based and therefore is unable to draw such conclusions. Nonetheless, the article in this issue of AJKD shows that an association exists between depression and factors that may lead to poor outcomes, including diabetes, prior psychiatric illness, drug and alcohol use, and use of antidepressant medications.8Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Prevalence of major depressive episode in CKD.Am J Kidney Dis. 2009; 54: 424-432Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar The biological rationale for poor outcomes with depressive symptoms is unclear. Depression results in abnormal hypothalamic-pituitary axis activity, with increased norepinephrine and cortisol secretion, which may have adverse consequences in a population with exorbitant rates of cardiovascular disease.24Otte C. Neylan T.C. Pipkin S.S. Browner W.S. Whooley M.A. Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with coronary disease: Findings from the Heart and Soul Study.Am J Psychiatry. 2005; 162: 2139-2145Crossref PubMed Scopus (86) Google Scholar Altered autonomic tone has been found in depressed patients after myocardial infarction.25Krittayaphong R. Cascio W.E. Light K.C. et al.Heart rate variability in patients with coronary artery disease: Differences in patients with higher and lower depression scores.Psychosom Med. 1997; 59: 231-235PubMed Google Scholar Additional abnormalities in serotonin levels lead to upregulation of platelet activation, with further potential for adverse cardiac events. The uremic milieu may cause a unique biological perturbation in patients with depression, with possible synergistic cardiac abnormalities. Uremia also may make patients more susceptible to mood disorders, but this is conjecture. The additional stressors faced by patients with CKD may both lead to depressive symptoms and hinder medical compliance, leading to worse care and outcomes.26Kimmel P.L. Cohen S.D. Peterson R.A. Depression in patients with chronic renal disease: Where are we going?.J Ren Nutr. 2008; 18: 99-103Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Research translating into improved care surrounding quality of life and depression is minimal, in part because of a paucity of outcome data for baseline issues.27Thombs B.D. Bassel M. Jewett L.R. Analyzing effectiveness of long-term psychodynamic psychotherapy.JAMA. 2009; 301 (author reply, 932-933): 930Crossref PubMed Scopus (15) Google Scholar How this information translates to the 26 million non–dialysis-dependent patients with CKD in this country is unclear.28Levey A.S. Coresh J. Balk E. et al.National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification.Ann Intern Med. 2003; 139: 137-147Crossref PubMed Scopus (3626) Google Scholar Improvement in care is unlikely to occur until an entity is recognized, studied, and treated. In 1 group of patients initiating dialysis therapy with BDI scores of 15 or higher, only 16% were receiving therapy.29Watnick S. Kirwin P. Mahnensmith R. Concato J. The prevalence and treatment of depression among patients starting dialysis.Am J Kidney Dis. 2003; 41: 105-110Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar In another group of dialysis patients, only half those offered treatment for depression accepted it.30Wuerth D. Finkelstein S.H. Ciarcia J. Peterson R. Kliger A.S. Finkelstein F.O. Identification and treatment of depression in a cohort of patients maintained on chronic peritoneal dialysis.Am J Kidney Dis. 2001; 37: 1011-1017Abstract Full Text PDF PubMed Scopus (113) Google Scholar In prior large randomized controlled trials, such as the Sertaline Antidepressant Heart Attack Randomized Trial (SADHART), patients with kidney disease were excluded.31Glassman A.H. O'Connor C.M. Califf R.M. et al.Sertraline treatment of major depression in patients with acute MI or unstable angina.JAMA. 2002; 288: 701-709Crossref PubMed Scopus (1231) Google Scholar Because our patients rarely are included in adequate trials of antidepressant therapy, we do not know the efficacy of treatment. Antidepressant trials of dialysis patients have had small sample sizes, lack of control groups, and inadequate follow-up. Side effects can compound symptoms and signs that our patients already experience. Central nervous system depression, increased bleeding risks, worsening nausea, sexual dysfunction, electrocardiogram abnormalities, and accumulation of toxic metabolites could be described in a brochure about either antidepressant side effects or advanced CKD. Other therapies, such as exercise and cognitive behavioral intervention, suggest a minimal positive effect.32Painter P. Physical functioning in end-stage renal disease patients: Update 2005.Hemodial Int. 2005; 9: 218-235Crossref PubMed Scopus (185) Google Scholar, 33Cukor D. Use of CBT to treat depression among patients on hemodialysis.Psychiatr Serv. 2007; 58: 711-712Crossref PubMed Scopus (30) Google Scholar Sadly, as we wonder about improvement in outcomes after therapy for depression in patients with CKD, we remain blinded. The state of affairs regarding care for these patients, simply put, is depressing. Extensive guidelines have been established addressing many of the numbers that go awry for our patients with CKD. However, when a patient walks through the door of the dialysis unit or a provider's office, the patient's first thought is not whether he or she has met Kidney Disease Outcomes Quality Initiative guidelines. A first thought might be: How will I feel today? How is this impacting my life? This reminds us to consider such issues as depression and quality of life alongside the traditional guidelines. Our goal is the betterment of the lives of our patients, and depression as it impacts on quality of life clearly is a field that requires further exploration. Future studies must assess long-term outcomes in patients with CKD and depression so that we better understand the implication of such a diagnosis. Subsequently, randomized controlled trials need to address the efficacy and tolerability of therapy as it pertains to our patients. The articles by Hedayati et al7Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Validation of depression screening scales in patients with CKD.Am J Kidney Dis. 2009; 54: 433-439Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 8Hedayati S.S. Minhajuddin A.T. Toto R.D. Morris D.W. Rush A.J. Prevalence of major depressive episode in CKD.Am J Kidney Dis. 2009; 54: 424-432Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar are a first step toward the day when our patients can not only hope for, but also expect, treatments for their kidney disease that encompass their physical and mental well-being. Financial Disclosure: None. Prevalence of Major Depressive Episode in CKDAmerican Journal of Kidney DiseasesVol. 54Issue 3PreviewDepression is prevalent in long-term dialysis patients and is associated with death and hospitalization. Whether depression is present through all chronic kidney disease (CKD) stages or appears after dialysis therapy initiation is not clear. We determined the prevalence of a major depressive episode and other psychiatric illnesses by using a structured gold-standard clinical interview and demographic and clinical variables associated with major depressive episode in patients with CKD. Full-Text PDF Validation of Depression Screening Scales in Patients With CKDAmerican Journal of Kidney DiseasesVol. 54Issue 3PreviewDepressive symptoms, assessed by using self-report scales, are present at a striking rate of 45% in patients with chronic kidney disease (CKD) at dialysis therapy initiation. These scales may emphasize somatic symptoms of anorexia, sleep disturbance, and fatigue, which may coexist with chronic disease symptoms and lead to overestimation of depression diagnosis. No study has validated these scales in patients with CKD before dialysis therapy initiation. Full-Text PDF