Original Paper Nephron Clin Pract 2014;128:22–28 DOI: 10.1159/000362453
Received: July 24, 2013 Accepted: March 24, 2014 Published online: October 29, 2014
Functional Status and Mortality in Chronic Kidney Disease: Results from a Prospective Observational Study James P. Ritchie Helen Alderson Darren Green Diana Chiu Smeeta Sinha Rachel Middleton Donal O’Donoghue Philip A. Kalra Vascular Research Group, Manchester Academic Health Science Center, Salford Royal Hospital, Salford, UK
Key Words Functional status · Mortality · Chronic kidney disease · Progression
Abstract Background/Aims: Measures of functional status are used in the general population to aid prognostication but their use has not been explored in pre-dialysis chronic kidney disease (CKD). This analysis considers the association between the Karnofsky performance score (KPS) and all-cause mortality in a CKD stage 3–5 cohort. Methods: Patients were selected from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS), a prospective observational study of outcome in CKD. Risk for death was assessed using multivariate Cox regression, and differences in progression of biochemical parameters were considered in a mixed-effects model. Results: A total of 1,515 patients with a median follow-up time of 2.9 (1.5–4.8) years were considered. Baseline age was 60 ± 11 years and eGFR was 30 ± 12 ml/min/1.73 m2. Patients with a reduced KPS had an increased risk for death. The hazard ratio (HR) for death was: KPS 90 group, HR 1.2 (95% CI 0.9–1.5), p = 0.1; KPS ≤80 group, HR 1.8 (95% CI 1.4–2.4), p < 0.001. In the mixed-effects model, the average annual loss of eGFR was greater in patients with a KPS ≤80 versus patients with a KPS >80 (5 vs. 3%, p = 0.008). Conclusion: A reduced KPS is independently associated with risk for mortality in patients with CKD stages 3–5. This may relate to a more rapid loss of eGFR.
Introduction
Chronic kidney disease (CKD) associates with excess morbidity and mortality, with risk for death increasing as the patient’s burden of co-morbidities accumulates [1]. Global assessments of health allow combined consideration of the effects of multiple concomitant diseases, with lower scores observed in patients with more disease processes [2]. These tools can assess quality of life and functional ability, with an inverse relationship existing between overall score and degree of renal impairment [3]. Given the association between co-morbid burden and risk for death in CKD, it is credible that global health assessments may aid in risk stratification [4, 5]. This hypothesis has been considered in haemodialysis patients [6], but no data exist to address the non-dialysis CKD population. As global health assessments can be more easily applied than detailed assessments of individual comorbidities, these tools have the potential to be rapidly applied in clinical practice. In this analysis, we test the hypothesis that reduced functional status in patients with all-cause CKD is an independent risk factor for mortality. Methods Patient Population Patients were selected from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS) [7]. Established in
© 2014 S. Karger AG, Basel © 2014 S. Karger AG, Basel 1660–2110/14/1282–0022$39.50/0 E-Mail [email protected] www.karger.com/nec
Dr. James P. Ritchie Department of Renal Medicine, Salford Royal Hospital Stott Lane Salford M6 8HD (UK) E-Mail jpritchie @ mac.com
Table 1. Grades of Karnofsky performance score
Score Functional status 100 Normal, no complaints, no signs of disease 90 Capable of normal activity, few symptoms or signs of disease 80 Normal activity with some difficulty, some symptoms or signs 70 Caring for self, not capable of normal activity or work 60 Requiring some help, can take care of most personal requirements 50 Requires help often, needs frequent medical care 40 Disabled, requires special care and help 30 Severely disabled, hospital admission indicated but no risk of death 20 Very ill, urgently requiring admission, requires supportive measures or treatment 10 Moribund, rapidly progressive fatal disease processes 0 Death
2002, this is a prospective observational study of outcome in patients with all-cause CKD managed in secondary care. All patients aged over 18 years at the time of referral to our nephrology unit for management of CKD are considered for recruitment. Patients expected to commence renal replacement therapy within 6 months are excluded, as are patients who have previously undergone kidney transplantation. Records are updated annually with details of demographic information, comorbid conditions, prescribed medications, blood pressure and laboratory measurements including renal function, proteinuria, haemoglobin and albumin. Pre-specified end-points are initiation of chronic renal replacement therapy, and death. Patient visits are conducted using a structured interview pro forma, with details corroborated against local electronic patient records. Mortality data are obtained from the Office of National Statistics. The local ethics committee granted approval for this study and all participants provided written informed consent. Entry into CRISIS does not affect patient management, with all patients treated to national and international targets [8, 9]. Assessment of Functional Status Since 2004, the functional status of all newly recruited patients has been documented using the Karnofsky score [10]. Here clinicians grade a patient’s performance score on a scale from 100 (perfect health) to 0 (death) in 10-unit intervals (table 1). Statistical Analysis Between-group comparisons for continuous baseline variables were made using ANOVA methodologies appropriate to the distribution of data. Normally distributed data are presented as mean ± SD; non-parametric data are presented as median (interquartile range). Categorical baseline variables were compared using the χ2 test. Survival analysis was performed using Cox proportional hazards regression and Kaplan-Meier analysis (log-rank test). Time zero was defined as date of Karnofsky score assessment (i.e. date of entry into the study). Censoring occurred at death or most recent clinical contact. Multivariate survival analysis was performed using a forward stepwise methodology with recorded variables either
Functional Status and Mortality in CKD
known to alter risk for death or with a statistically significant and clinically plausible relationship in this cohort included (α value for inclusion
Received: July 24, 2013 Accepted: March 24, 2014 Published online: October 29, 2014
Functional Status and Mortality in Chronic Kidney Disease: Results from a Prospective Observational Study James P. Ritchie Helen Alderson Darren Green Diana Chiu Smeeta Sinha Rachel Middleton Donal O’Donoghue Philip A. Kalra Vascular Research Group, Manchester Academic Health Science Center, Salford Royal Hospital, Salford, UK
Key Words Functional status · Mortality · Chronic kidney disease · Progression
Abstract Background/Aims: Measures of functional status are used in the general population to aid prognostication but their use has not been explored in pre-dialysis chronic kidney disease (CKD). This analysis considers the association between the Karnofsky performance score (KPS) and all-cause mortality in a CKD stage 3–5 cohort. Methods: Patients were selected from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS), a prospective observational study of outcome in CKD. Risk for death was assessed using multivariate Cox regression, and differences in progression of biochemical parameters were considered in a mixed-effects model. Results: A total of 1,515 patients with a median follow-up time of 2.9 (1.5–4.8) years were considered. Baseline age was 60 ± 11 years and eGFR was 30 ± 12 ml/min/1.73 m2. Patients with a reduced KPS had an increased risk for death. The hazard ratio (HR) for death was: KPS 90 group, HR 1.2 (95% CI 0.9–1.5), p = 0.1; KPS ≤80 group, HR 1.8 (95% CI 1.4–2.4), p < 0.001. In the mixed-effects model, the average annual loss of eGFR was greater in patients with a KPS ≤80 versus patients with a KPS >80 (5 vs. 3%, p = 0.008). Conclusion: A reduced KPS is independently associated with risk for mortality in patients with CKD stages 3–5. This may relate to a more rapid loss of eGFR.
Introduction
Chronic kidney disease (CKD) associates with excess morbidity and mortality, with risk for death increasing as the patient’s burden of co-morbidities accumulates [1]. Global assessments of health allow combined consideration of the effects of multiple concomitant diseases, with lower scores observed in patients with more disease processes [2]. These tools can assess quality of life and functional ability, with an inverse relationship existing between overall score and degree of renal impairment [3]. Given the association between co-morbid burden and risk for death in CKD, it is credible that global health assessments may aid in risk stratification [4, 5]. This hypothesis has been considered in haemodialysis patients [6], but no data exist to address the non-dialysis CKD population. As global health assessments can be more easily applied than detailed assessments of individual comorbidities, these tools have the potential to be rapidly applied in clinical practice. In this analysis, we test the hypothesis that reduced functional status in patients with all-cause CKD is an independent risk factor for mortality. Methods Patient Population Patients were selected from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS) [7]. Established in
© 2014 S. Karger AG, Basel © 2014 S. Karger AG, Basel 1660–2110/14/1282–0022$39.50/0 E-Mail [email protected] www.karger.com/nec
Dr. James P. Ritchie Department of Renal Medicine, Salford Royal Hospital Stott Lane Salford M6 8HD (UK) E-Mail jpritchie @ mac.com
Table 1. Grades of Karnofsky performance score
Score Functional status 100 Normal, no complaints, no signs of disease 90 Capable of normal activity, few symptoms or signs of disease 80 Normal activity with some difficulty, some symptoms or signs 70 Caring for self, not capable of normal activity or work 60 Requiring some help, can take care of most personal requirements 50 Requires help often, needs frequent medical care 40 Disabled, requires special care and help 30 Severely disabled, hospital admission indicated but no risk of death 20 Very ill, urgently requiring admission, requires supportive measures or treatment 10 Moribund, rapidly progressive fatal disease processes 0 Death
2002, this is a prospective observational study of outcome in patients with all-cause CKD managed in secondary care. All patients aged over 18 years at the time of referral to our nephrology unit for management of CKD are considered for recruitment. Patients expected to commence renal replacement therapy within 6 months are excluded, as are patients who have previously undergone kidney transplantation. Records are updated annually with details of demographic information, comorbid conditions, prescribed medications, blood pressure and laboratory measurements including renal function, proteinuria, haemoglobin and albumin. Pre-specified end-points are initiation of chronic renal replacement therapy, and death. Patient visits are conducted using a structured interview pro forma, with details corroborated against local electronic patient records. Mortality data are obtained from the Office of National Statistics. The local ethics committee granted approval for this study and all participants provided written informed consent. Entry into CRISIS does not affect patient management, with all patients treated to national and international targets [8, 9]. Assessment of Functional Status Since 2004, the functional status of all newly recruited patients has been documented using the Karnofsky score [10]. Here clinicians grade a patient’s performance score on a scale from 100 (perfect health) to 0 (death) in 10-unit intervals (table 1). Statistical Analysis Between-group comparisons for continuous baseline variables were made using ANOVA methodologies appropriate to the distribution of data. Normally distributed data are presented as mean ± SD; non-parametric data are presented as median (interquartile range). Categorical baseline variables were compared using the χ2 test. Survival analysis was performed using Cox proportional hazards regression and Kaplan-Meier analysis (log-rank test). Time zero was defined as date of Karnofsky score assessment (i.e. date of entry into the study). Censoring occurred at death or most recent clinical contact. Multivariate survival analysis was performed using a forward stepwise methodology with recorded variables either
Functional Status and Mortality in CKD
known to alter risk for death or with a statistically significant and clinically plausible relationship in this cohort included (α value for inclusion
