Fatigue in Patients Receiving Maintenance Hemodialysis: A Review.

Fatigue surrounding hemodialysis treatments is a common and often debilitating symptom that impacts patients' quality of life. Intradialytic fatigue develops or worsens immediately before hemodialysis and persists through the dialysis treatment. Little is known about associated risk factors or pathophysiology, although it may relate to a classic conditioning response. Postdialysis fatigue (PDF) develops or worsens after hemodialysis and may persist for hours. There is no consensus on how to measure PDF. Estimates for the prevalence of PDF range from 20%-86%, likely due to variation in methods of ascertainment and participant characteristics. Several hypotheses seek to explain the pathophysiology of PDF, including inflammation, hypothalamic-pituitary-adrenal axis dysregulation, and osmotic and fluid shifts, but none is currently supported by compelling or consistent data. PDF is associated with several clinical factors, including cardiovascular and hemodynamic effects of the dialysis procedure, laboratory abnormalities, depression, and physical inactivity. Clinical trials have reported hypothesis-generating data about the utility of cold dialysate, frequent dialysis, clearance of large middle molecules, treatment of depression, and exercise as potential treatments. Existing studies are often limited by sample size, lack of a control group, observational design, or short intervention duration. Robust studies are needed to establish the pathophysiology and management of this important symptom.

Predictors, Disparities, and Facility-Level Variation: SGLT2 Inhibitor Prescription Among US Veterans With CKD.

RATIONALE & OBJECTIVE: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are recommended for type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease (CKD) or atherosclerotic cardiovascular disease (ASCVD). We evaluated factors associated with SGLT2 inhibitor prescription, disparities by race and sex, and facility-level variation in prescription patterns. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: A national sample of US veterans with comorbid T2DM, CKD, and ASCVD with a primary care visit between January 1 and December 31, 2020. EXPOSURE: Race, sex, and individual Veterans Affairs (VA) location. OUTCOME: SGLT2 inhibitor prescription. ANALYTICAL APPROACH: Multivariable logistic regression assessed associations of race and sex with SGLT2 inhibitor prescription. Facility-level variation in SGLT2i prescription was quantified by median rate ratios (MRR), which express the likelihood that 2 randomly selected facilities differ in their use of SGLT2 inhibitor among similar patients. RESULTS: Of 174,443 patients with CKD, T2DM, and ASCVD, 20,024 (11.5%) were prescribed an SGLT2 inhibitor. Lower odds of SGLT2 inhibitor prescription were seen in Black or African American patients compared with White patients (OR, 0.87 [95% CI, 0.83-0.91]) and among women compared with men (OR, 0.59 [95% CI 0.52-0.67]). The adjusted MRR for SGLT2 inhibitor prescription was 1.58 (95% CI 1.48-1.67) in the total cohort, indicating an unexplained 58% variation in treatment between VA facilities, independent of patient and facility characteristics. Facility-level variation was evaluated among Black or African American patients (MRR, 1.55 [95% CI 1.41-1.68]), White patients (MRR, 1.57 [95% CI 1.47-1.66]), women (MRR, 1.40 [95% CI 1.28-1.51]), and men (MRR, 1.57 [95% CI 1.48-1.67]). LIMITATIONS: Albuminuria was not assessed. CONCLUSIONS: Prescription for SGLT2 inhibitors was low among likely eligible patients, with evident disparities by sex and race and between individual VA facilities. Efforts are needed to study and address the reasons for these disparities to improve equitable adoption of these important medications.

Documented Adverse Drug Reactions and Discontinuation of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Chronic Kidney Disease.

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation. METHODS: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented ADRs with treatment discontinuation. RESULTS: There were 882,441 (73.0%) individuals in the current user group and 326,794 (27.0%) in the discontinued group. There were 26,434 documented ADRs, with at least one documented ADR in 7,520 (0.9%) current users and 9,569 (2.9%) of the discontinued group. ADR presence was associated with treatment discontinuation, aOR 4.16 (95% CI: 4.03, 4.29). The most common documented ADRs were cough (37.3%), angioedema (14.2%), and allergic reaction (10.4%). ADRs related to angioedema (aOR 3.81, 95% CI: 3.47, 4.17), hyperkalemia (aOR 2.03, 95% CI: 1.84, 2.24), peripheral edema (aOR 1.53, 95% CI: 1.33, 1.77), or acute kidney injury (aOR 1.32, 95% CI: 1.15, 1.51) were associated with treatment discontinuation. CONCLUSION: ADRs leading to drug discontinuation were infrequently documented. ADR types were differentially associated with treatment discontinuation. An understanding of which ADRs lead to treatment discontinuation provides an opportunity to address them at a healthcare system level.

Steroidal or non-steroidal MRAs: should we still enable RAASi use through K binders?

Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions in the lumen of the gastrointestinal tract to prevent the absorption of dietary potassium and increase potassium secretion. Several studies showed that potassium binders are effective compared with placebo for preventing hyperkalemia or steroidal MRA discontinuation, but none has evaluated whether this strategy impacts clinically important endpoints such as cardiovascular events. Due to this and other limitations related to cost, clinical availability, pill burden and patient selection, alternative potential strategies to mitigate hyperkalemia may be more practical. Conservative strategies include increased monitoring and use of loop or thiazide diuretics to increase urinary potassium excretion. Non-steroidal MRAs may have a lower risk of hyperkalemia than steroidal MRAs and have stronger anti-inflammatory and anti-fibrotic effects with resultant reduced risk of kidney disease progression. Sodium-glucose cotransporter-2 inhibitors also decrease hyperkalemia risk in patients on MRAs and decrease cardiovascular events and kidney disease progression. These may be better first-line interventions to obviate the need for potassium binders and offer additional benefits.

Correlates of SGLT-2-inhibitiors use among patients with atherosclerotic cardiovascular disease and type 2 diabetes mellitus: Insights from the department of veterans affairs.

This study using data from the Veterans Affairs (VA) administrative and clinical dataset examined determinants of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) use among patients with concomitant atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus. The aim of the present analysis was to identify barriers and facilitators associated with SGLT-2i in a real-world contemporary patient population in order to improve utilization of these guideline-directed agents.

Heart failure-type symptom scores in chronic kidney disease: The importance of body mass index.

OBJECTIVES: This analysis sought to determine factors (including adiposity-related factors) most associated with HF-type symptoms (fatigue, shortness of breath, and edema) in adults with chronic kidney disease (CKD). BACKGROUND: Symptom burden impairs quality of life in CKD, especially symptoms that overlap with HF. These symptoms are common regardless of clinical HF diagnosis, and may be affected by subtle cardiac dysfunction, kidney dysfunction, and other factors. We used machine learning to investigate cross-sectional relationships of clinical variables with symptom scores in a CKD cohort. METHODS: Participants in the Chronic Renal Insufficiency Cohort (CRIC) with a baseline modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score were included, regardless of prior HF diagnosis. The primary outcome was Overall Summary Score as a continuous measure. Predictors were 99 clinical variables representing demographic, cardiac, kidney and other health dimensions. A correlation filter was applied. Random forest regression models were fitted. Variable importance scores and adjusted predicted outcomes are presented. RESULTS: The cohort included 3426 individuals, 10.3% with prior HF diagnosis. BMI was the most important factor, with BMI 24.3 kg/m2 associated with the least symptoms. Symptoms worsened with higher or lower BMIs, with a potentially clinically relevant 5 point score decline at 35.7 kg/m2 and a 1-point decline at the threshold for low BMI, 18.5 kg/m2. The most important cardiac and kidney factors were heart rate and eGFR, the 4th and 5th most important variables, respectively. Results were similar for secondary analyses. CONCLUSIONS: In a CKD cohort, BMI was the most important feature for explaining HF-type symptoms regardless of clinical HF diagnosis, identifying an important focus for symptom directed investigations.

Revisiting diuretic choice in chronic kidney disease.

PURPOSE OF REVIEW: Existing guidelines offer little direction about the use of thiazide and loop diuretics in patients with chronic kidney disease (CKD). This review summarizes recent studies impacting indications and safety considerations for these agents in patients with CKD. RECENT FINDINGS: Chlorthalidone reduces blood pressure compared to placebo in patients with advanced CKD, challenging the belief that thiazide diuretics lose efficacy at lower glomerular filtration rates (GFR). Existing studies show no clear impact of thiazide or loop diuretic use on kidney or cardiovascular outcomes in patients with CKD. Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have diuretic effects, but concomitant use of a diuretic does not diminish the preventive benefits of these agents against acute kidney injury (AKI). Despite theoretical concerns, thiazide diuretics likely do not worsen circulating vasopressin levels or cyst progression in polycystic kidney disease and may be useful for alleviating polyuria from tolvaptan. Diuretics cause multiple adverse effects, including electrolyte abnormalities, hemodynamic-mediated decrease in estimated GFR, and AKI. SUMMARY: Recent evidence supports expanded indications for diuretics in patients with kidney disease, including chlorthalidone for hypertension in advanced CKD. Monitoring electrolytes and estimated GFR is critical to ensure patient safety when prescribing these agents for patients with CKD.

Using dipstick urinalysis to predict development of acute kidney injury in patients with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients hospitalized with COVID-19 and may require renal replacement therapy (RRT). Dipstick urinalysis is frequently obtained, but data regarding the prognostic value of hematuria and proteinuria for kidney outcomes is scarce. METHODS: Patients with positive severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) PCR, who had a urinalysis obtained on admission to one of 20 hospitals, were included. Nested models with degree of hematuria and proteinuria were used to predict AKI and RRT during admission. Presence of Chronic Kidney Disease (CKD) and baseline serum creatinine were added to test improvement in model fit. RESULTS: Of 5,980 individuals, 829 (13.9%) developed an AKI during admission, and 149 (18.0%) of those with AKI received RRT. Proteinuria and hematuria degrees significantly increased with AKI severity (P < 0.001 for both). Any degree of proteinuria and hematuria was associated with an increased risk of AKI and RRT. In predictive models for AKI, presence of CKD improved the area under the curve (AUC) (95% confidence interval) to 0.73 (0.71, 0.75), P < 0.001, and adding baseline creatinine improved the AUC to 0.85 (0.83, 0.86), P < 0.001, when compared to the base model AUC using only proteinuria and hematuria, AUC = 0.64 (0.62, 0.67). In RRT models, CKD status improved the AUC to 0.78 (0.75, 0.82), P < 0.001, and baseline creatinine improved the AUC to 0.84 (0.80, 0.88), P < 0.001, compared to the base model, AUC = 0.72 (0.68, 0.76). There was no significant improvement in model discrimination when both CKD and baseline serum creatinine were included. CONCLUSIONS: Proteinuria and hematuria values on dipstick urinalysis can be utilized to predict AKI and RRT in hospitalized patients with COVID-19. We derived formulas using these two readily available values to help prognosticate kidney outcomes in these patients. Furthermore, the incorporation of CKD or baseline creatinine increases the accuracy of these formulas.

Improving chronic kidney disease detection and treatment in the United States: the chronic kidney disease cascade of care (C3) study protocol.

BACKGROUND: There are major gaps in the implementation of guideline-concordant care for persons with chronic kidney disease (CKD). The CKD Cascade of Care (C3) initiative seeks to improve CKD care by improving detection and treatment of CKD in primary care. METHODS: C3 is a multi-modal initiative deployed in three major academic medical centers within the Department of Veterans Affairs (VA) Health Care System: San Francisco VA, San Diego VA, and Houston VA. The main objective of the first phase of C3 described in this protocol is to establish the infrastructure for universal CKD detection among primary care patients at high-risk for CKD with a triple-marker screen comprising cystatin C, creatinine, and albuminuria. Across the three sites, a comprehensive educational intervention and the integration of primary care-based clinical champions will be employed with the goal of improving CKD detection and treatment. The San Francisco VA will also implement a practice-facilitation intervention leveraging telehealth and health informatics tools and capabilities for enhanced CKD detection. Parallel formative evaluation across the three sites will assess the feasibility and acceptability of integrating cystatin C as part of routine CKD detection in primary care practice. The effectiveness of the interventions will be assessed using a pre-post observational design for change in the proportion of patients tested annually for CKD. Secondary outcomes will assess change in the initiation of cardio-kidney protective therapies and in nephrology referrals of high-risk patients. DISCUSSION: The first phase of C3 is a multi-facility multi-modal initiative that aims to improve CKD care by implementing a triple-marker screen for enhanced CKD detection in primary care.

Early eGFR decline after SGLT2i initiation: knowns and unknowns.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve kidney and cardiovascular outcomes. SLGT2i initiation is accompanied by an acute decline in glomerular filtration rate. However, the clinical significance of this acute change remains unclear. In this issue of Kidney International, Kraus et al. examined the factors associated with an initial decline in estimated glomerular filtration rate after starting empagliflozin or placebo, subsequent kidney function trajectory, and the associations of odds of initial estimated glomerular filtration rate dip with long-term cardiovascular and kidney outcomes.

Mortality, Kidney Failure, and Hospitalization Among Medicare Beneficiaries With CKD and Pulmonary Hypertension.

RATIONALE & OBJECTIVE: Pulmonary hypertension (PH) is highly prevalent among patients with chronic kidney disease (CKD) not requiring kidney replacement therapy. We studied the associations of PH with mortality, kidney failure, as well as cardiovascular (CV) and non-CV hospitalization among Medicare beneficiaries with a CKD diagnosis. STUDY DESIGN: Retrospective, observational study using a matched cohort design. SETTING & PARTICIPANTS: Patients with PH (based on 2 claims within 2 years) and patients without PH matched on CKD stage from the Medicare 5% CKD sample (1996-2016). PREDICTOR: Presence of pulmonary hypertension. OUTCOME: Mortality, kidney failure, and all-cause, CV, and non-CV hospitalization. ANALYTICAL APPROACH: Cox proportional hazards models to assess the association between PH and mortality, adjusting for age, sex, race, and comorbidities. Death was considered as a competing event in Fine-Gray models to assess the association between PH and kidney failure. Negative binomial model was used to evaluate the relationship between PH and all-cause, CV, and non-CV hospitalizations. RESULTS: 30,052 patients with PH and CKD and 150,260 CKD stage-matched patients without diagnosed PH were studied. The median age of the study population was 80.7 years, 57.8% were women, and 10.3% were African Americans. The presence of PH was associated with an increased risk of mortality after 1 (HR, 2.87 [95% CI, 2.79-2.95]), 2-3 (HR, 1.56 [95% CI, 1.51-1.61]), and 4-5 (HR, 1.47 [95% CI, 1.40-1.53]) years of follow-up, and a higher risk of all-cause, CV, and non-CV hospitalization during the same period. PH was also associated with kidney failure in after 1 and 2-3 years but not after 4-5 years of follow-up evaluation. Patients with PH also experienced higher rates of acute kidney injury (AKI), and AKI requiring dialysis support within 30 and 90 days of AKI. LIMITATIONS: Reliance on billing codes and lack of echocardiogram or right heart catheterization data CONCLUSIONS: Among older Medicare beneficiaries with a CKD diagnosis not requiring kidney replacement therapy, the presence of PH was associated with an increased risk of mortality, kidney failure, and hospitalization. Understanding of the mechanism of these associations, especially the increased risk of kidney failure, requires further study.

Pharmacologic and psychological interventions for depression treatment in patients with kidney disease.

PURPOSE OF REVIEW: It remains controversial whether existing therapies, including pharmacologic and psychological interventions, are effective for treatment of depression in patients with chronic kidney disease (CKD) and end-stage kidney disease. RECENT FINDINGS: Most studies of depression treatment were underpowered or uncontrolled. The CKD Antidepressant Sertraline Trial showed no benefit of a serotonin-selective reuptake inhibitor (SSRI), sertraline, over double-blind matched placebo for the treatment of depressive symptoms in patients with nondialysis CKD. A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression showed improvement in depressive symptoms from baseline in both groups and a marginal benefit of sertraline over CBT that was of unclear clinical significance, given the lack of an active control group. SSRIs are associated with poor tolerability in clinical trials and serious adverse outcomes in large retrospective studies. SUMMARY: Although the data do not support unlimited use of SSRIs in patients with CKD or end-stage kidney disease, it is reasonable to initiate a cautious trial of sertraline while closely monitoring for depressive symptom improvement and adverse effects. CBT is a low-risk, possibly effective intervention to treat major depressive disorder in patients with kidney disease who have access to such treatments.

Fatigue in Nondialysis Chronic Kidney Disease: Correlates and Association with Kidney Outcomes.

BACKGROUND: Fatigue, although common and associated with outcomes in dialysis-dependent chronic kidney disease (CKD), has not been studied in nondialysis chronic kidney disease (CKD-ND) patients. METHODS: In this longitudinal cohort of 266 outpatients with CKD-ND stages 2-5, we measured self-reported fatigue on 3 scales-Quick Inventory of Depression Symptomatology-Self Report (QIDS-SR16), Beck Depression Inventory-I (BDI-I), and short form 12 health survey (SF-12) questionnaires and evaluated the prespecified composite of progression to dialysis initiation, death, or hospitalization after 12 months. Logistic and linear regression assessed characteristics associated with fatigue. Survival analysis measured associations of fatigue with outcomes. RESULTS: Mean age was 64.4 ± 12.0 years, and mean estimated glomerular filtration rate (eGFR) was 31.6 ± 16.7 mL/min/1.73 m2. Fatigue was common, with 69.2% reporting fatigue on QIDS-SR16 and 77.7% on BDI-I. Unemployment, comorbidities, use of antidepressant medications, and lower hemoglobin correlated with fatigue. There were 126 outcome events. Participants that reported any versus no fatigue on QIDS-SR16 were more likely to reach the composite, hazard ratio (HR) 1.70 (95% CI 1.11-2.59), which persisted after adjusting for demographics, comorbidities, substance abuse, hemoglobin, albumin, eGFR, and calcium-phosphorus product, HR 1.63 (1.05-2.55). Fatigue severity by the SF-12 was also associated with outcomes independent of demographics, comorbidities, and substance abuse, HR per unit increase 1.18 (1.03-1.35). No association was observed with fatigue on the BDI-I. CONCLUSION: Fatigue affected about 2/3 of CKD-ND patients and associated with unemployment, comorbidities, antidepressant medication use, and anemia. Fatigue measured by the QIDS-SR16 and SF-12 independently predicted outcomes in CKD patients. Eliciting the presence of fatigue may be a clinically significant prognostic assessment in CKD patients.

Management of Traditional Cardiovascular Risk Factors in CKD: What Are the Data?

Patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) are 10 times more likely to die of cardiovascular (CV) diseases than the general population, and dialysis-dependent patients are at even higher risk. Although traditional CV risk factors are highly prevalent in individuals with CKD, these patients were often excluded from studies targeting modification of these risks. Although treatment of hypertension is beneficial in CKD, the best target blood pressure has not been established. Trial data showed that renin-angiotensin-aldosterone blockade may prevent CV events in patients with CKD. The risks of aspirin may equal the benefits in NDD-CKD samples, and there are no trials testing aspirin in dialysis-dependent patients. Lipid-lowering therapy improves CV outcomes in NDD-CKD, but not in dialysis-dependent patients. Strict glycemic control prevents CV events in nonalbuminuric individuals, but showed no benefit in those with baseline albuminuria with albumin excretion > 300mg/g, and there are no data in dialysis-dependent patients. Data for lifestyle modifications, such as weight loss, physical activity, and smoking cessation, are mostly observational and extrapolated from non-CKD samples. This comprehensive review summarizes the best existing evidence and current clinical guidelines for modification of traditional risk factors for the prevention of CV events in patients with CKD and identifies knowledge gaps.

Association of Monocyte Chemoattractant Protein-1 with Death and Atherosclerotic Events in Chronic Kidney Disease.

BACKGROUND: Monocyte chemoattractant protein-1 -(MCP-1), a marker of inflammation and monocyte recruitment to atherosclerotic plaques, is associated with cardiovascular (CV) outcomes in patients with acute coronary syndrome. Although plasma levels are elevated in chronic kidney disease (CKD), associations with reduced kidney function or outcomes in CKD have not been explored. METHODS: In this population-based, probability-sampled, longitudinal cohort of 3,257 participants, including 286 (8.8%) patients with CKD, we studied the association of plasma MCP-1 with estimated glomerular filtration rate (eGFR), albuminuria, death, and intermediate and hard CV outcomes in CKD and non-CKD individuals. Cox proportional hazards regression assessed associations of baseline MCP-1 with all-cause death and atherosclerotic events. RESULTS: MCP-1 was higher in CKD than non-CKD participants (p < 0.001), and negatively associated with eGFR (r = -0.23, p < 0.0001) but not albuminuria in CKD. MCP-1 was associated with pulse wave velocity and coronary artery calcification in non-CKD but not CKD individuals. At 13.5 years, there were 230 (7.7%) deaths and 168 (6.4%) atherosclerotic events in the non-CKD vs. 97 (34.0%) deaths and 62 (27.9%) events in the CKD group (p < 0.001 for each). MCP-1 was associated with death (hazards ratio [HR] 2.0 [1.4-2.9] per log-unit increase) and atherosclerotic events (1.7 [1.0-2.9]) in CKD individuals. The HR for death in CKD remained significant (1.6 [1.1-2.3]) after adjusting for CV risk factors. CONCLUSIONS: Although plasma MCP-1 increased with decreased eGFR, it remained an independent risk factor for death in CKD. MCP-1 did not correlate with intermediate CV outcomes, implicating pathways other than atherosclerosis in the association of MCP-1 with death in CKD.

Effect of Sertraline on Depressive Symptoms in Patients With Chronic Kidney Disease Without Dialysis Dependence: The CAST Randomized Clinical Trial.

Importance: Major depressive disorder (MDD) is prevalent among patients with chronic kidney disease (CKD) and is associated with morbidity and mortality. The efficacy and adverse events of selective serotonin reuptake inhibitors in these patients are unknown. Objective: To determine whether treatment with sertraline improves depressive symptoms in patients with CKD and MDD. Design, Setting, and Participants: The Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) was a randomized, double-blind, placebo-controlled trial involving 201 patients with stage 3, 4, or 5 non-dialysis-dependent CKD, who were enrolled at 3 US medical centers. The Mini Neuropsychiatric Interview was used to establish MDD. The first participant was randomized in March 2010 and the last clinic visit occurred in November 2016. Interventions: After a 1-week placebo run-in, participants were randomized to sertraline (n = 102) for 12 weeks at an initial dose of 50 mg/d (escalated to a maximum dose of 200 mg/d based on tolerability and response) or matching placebo (n = 99). Main Outcomes and Measures: The primary outcome was improvement in depressive symptom severity from baseline to 12 weeks determined by the 16-item Quick Inventory of Depression Symptomatology-Clinician Rated (QIDS-C16) (score range, 0-27; minimal clinically important difference, 2 points). Secondary outcomes included improvement in quality of life (Kidney Disease Quality of Life Survey-Short Form; score range, 0-100; higher scores indicate more favorable quality of life) and adverse events. Results: There were 201 patients (mean [SD] age, 58.2 [13.2] years; 27% female) randomized. The primary analysis included 193 patients who had at least 1 outcome assessment after randomization. The mean (SD) baseline QIDS-C16 score was 14.0 (2.4) in the sertraline group (n = 97) and 14.1 (2.4) in the placebo group (n = 96). The median participation time was 12.0 weeks and the median achieved dose was 150 mg/d, which was not significantly different between the groups. The QIDS-C16 score changed by -4.1 in the sertraline group and by -4.2 in the placebo group (between-group difference, 0.1 [95% CI, -1.1 to 1.3]; P = .82). There was no significant between-group difference in change in patient-reported overall health on the Kidney Disease Quality of Life Survey (median score, 0 in the sertraline group vs 0 in the placebo group; between-group difference, 0 [95% CI, -10.0 to 0]; P = .61). Nausea or vomiting occurred more frequently in the sertraline vs placebo group (22.7% vs 10.4%, respectively; between-group difference, 12.3% [95% CI, 1.9% to 22.6%], P = .03), as well as diarrhea (13.4% vs 3.1%; between-group difference, 10.3% [95% CI, 2.7% to 17.9%], P = .02). Conclusions and Relevance: Among patients with non-dialysis-dependent CKD and MDD, treatment with sertraline compared with placebo for 12 weeks did not significantly improve depressive symptoms. These findings do not support the use of sertraline to treat MDD in patients with non-dialysis-dependent CKD. Trial Registration: clinicaltrials.gov Identifier: NCT00946998.