Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Course of symptoms and health-related quality of life during specialized pre-dialysis care.

BackgroundConcerns are present on the limited value of renal function alone in defining the optimal moment to start dialysis. Disease-related symptoms and health-related quality of life (HRQOL) may have additional clinical value in defining this moment, but little is known about how these parameters change during pre-dialysis care. The aims of our study were to describe the course of symptoms and HRQOL during pre-dialysis care and to investigate their association with poor health outcomes.MethodsIn the prospective PREPARE-2 cohort, incident patients starting specialized pre-dialysis care were included when referred to one of the 25 participating Dutch outpatient clinics (2004-2011). In the present analysis, 436 patients with data available on symptoms and HRQOL were included. Clinical data, symptoms (revised illness perception questionnaire), and HRQOL (short form-36 questionnaire; physical and mental summary score) were collected every 6-month interval. A time-dependent Cox proportional hazard model was used to associate symptoms and HRQOL with the combined poor health outcome (i.e. starting dialysis, receiving a kidney transplant, and death).ResultsAll symptoms increased, especially fatigue and loss of strength, and both the physical and mental summary score decreased over time, with the most pronounced change during the last 6-12 months of follow-up. Furthermore, each additional symptom (adjusted HR 1.04 (95% CI, 1.00-1.09)) and each 3-point lower physical and mental summary score (adjusted HR 1.04 (1.02-1.06) and 1.04 (1.02-1.06) respectively) were associated with a higher risk of reaching the combined poor health outcome within the subsequent 6 months.ConclusionsThe number of symptoms increased and both the physical and mental HRQOL score decreased during pre-dialysis care and these changes were associated with starting dialysis, receiving a kidney transplant, and death. These results may indicate that symptoms and HRQOL are good markers for the medical condition and disease stage of pre-dialysis patients

Baseline characteristics for total population and stratified by type of endpoint.

<p>Median (boundaries of interquartile range) is given for age and proteinuria and mean ± standard deviation is given for all other normally distributed continuous variables.</p>∧<p>Defined as starting dialysis, receiving a kidney transplant, and death.</p><p>*Available for 428 patients.</p>†<p>Estimated glomerular filtration rate (eGFR) is calculated with the 4-variable Modification of Diet in Renal Disease formula and available for 379 patients.</p>§<p>Available for 225 patients.</p>•<p>Available for 365 patients.</p>□<p>Creatinine clearance is estimated with the formula creatinine in urine (mmol/24 h) * 700/serum creatinine (μmol/l), normalized per 1.73 m² of body surface area and available for 242 patients.</p>Δ<p>Available for 432 patients.</p><p>**Available for 378 patients.</p>‡<p>Available for 377 patients.</p>••<p>Available for 223 patients.</p>□□<p>Defined as presence of a cerebrovascular accident, vascular problems, angina pectoris, myocardial infarction, or decompensatio cordis.</p>ΔΔ<p>Present as primary kidney disease or comorbidity.</p

Association of symptoms and a low HRQOL with the risk of starting dialysis within the subsequent 6 months based on separate time-dependent Cox proportional hazard models.

<p>The HR with its 95% confidence interval (CI) represents the increased risk of starting dialysis within the subsequent 6 months in patients with the symptom compared to patients without the symptom present, the increased risk with each additional symptom, and the increased risk with every 3-point lower physical and mental summary score. A decrease of 3 score points is considered to be clinically relevant. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093069#pone.0093069-Leaf1" target="_blank">[43]</a>.</p>§<p>Adjusted for age, sex, diabetes mellitus, cardiovascular disease, and time dependent eGFR.</p><p>*p<0.05;</p><p>**p<0.005.</p

Course of symptoms during pre-dialysis care.

<p>The course of the total number of symptoms is presented for the total population (A) and stratified by the type of endpoint reached (combined poor health outcome; dialysis/transplantation/death, or end of follow-up/other endpoint, B). The black and grey dots indicate the mean and the error bars indicate the standard error of the mean (SEM). The time in months before reaching an endpoint is presented on the x-axis (−12 means that the measurement was 7–12 months before reaching an endpoint, −18 means 13–18 months etc). On the y-axis, the mean (SEM) total number of symptoms is presented, which can range from 0 to 12.</p

Course of eGFR and CrCl during pre-dialysis care.

<p>The course of eGFR and CrCl are presented for the total population (A) and stratified by the type of endpoint reached (combined poor health outcome; dialysis/transplantation/death, or end of follow-up/other endpoint, B). The black and grey dots indicate the mean and the error bars indicate the standard error of the mean (SEM). The time in months before reaching an endpoint is presented on the x-axis (−12 means that the measurement was 7–12 months before the moment of reaching an endpoint, −18 means 13–18 months etc). On the left y-axis, the mean (SEM) eGFR (ml/min/1.73 m²) is presented, and on the right y-axis the mean (SEM) CrCl (ml/min/1.73 m²).</p

Association of symptoms and a low HRQOL with the risk of reaching the combined poor health outcome within the subsequent 6 months based on separate time-dependent Cox proportional hazard models.

<p>The HR with its 95% confidence interval (CI) represents the increased risk of reaching the combined poor health outcome (dialysis, transplantation, and death) within the subsequent 6 months in patients with the symptom compared to patients without the symptom present, the increased risk with each additional symptom, and the increased risk with every 3-point lower physical and mental summary score. A decrease of 3 score points is considered to be clinically relevant. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093069#pone.0093069-Leaf1" target="_blank">[43]</a></p>§<p>Adjusted for age, sex, diabetes mellitus, cardiovascular disease, and time dependent eGFR.</p><p>*p<0.05;</p><p>**p<0.005.</p

Course of HRQOL during pre-dialysis care.

<p>The course of the physical and mental summary score are presented for the total population (A) and stratified by the type of endpoint reached (combined poor health outcome; dialysis/transplantation/death, or end of follow-up/other endpoint, B). The black and grey dots indicate the mean and the error bars indicate the standard error of the mean (SEM). The time in months before reaching an endpoint is presented on the x-axis (−12 means that the measurement was 7–12 months before the moment of reaching an endpoint, −18 means 13–18 months etc). On the y-axis, the mean (SEM) score from the SF-36 questionnaire is presented (separately for the physical and mental summary measure), which can range from 0 to 100.</p