How to adjust for comorbidity in survival studies in ESRD patients: A comparison of different indices

doi:10.1053/ajkd.2002.33916

American Journal of Kidney Diseases

Volume 40, Issue 1, July 2002, Pages 82-89

https://doi.org/10.1053/ajkd.2002.33916 Get rights and content

Abstract

Background: Many patients with end-stage renal disease (ESRD) have additional comorbid conditions. Differences in the presence and severity of these comorbid conditions can bias comparisons between treatment groups. Adjustment for prognostic factors can statistically counterbalance these differences. For this purpose, appropriate weighting of comorbid conditions is necessary. We evaluated three existing methods to score comorbidity in patients with ESRD and compared their ability to predict survival: the Khan, Davies, and Charlson indices. In addition, these three indices were compared with a new index that explicitly incorporates the severity grading of a number of comorbid diseases. Methods: In a large Dutch prospective multicenter study (Netherlands Co-operative Study on the Adequacy of Dialysis-2), new patients with ESRD were included. Comorbidity was assessed at the start of dialysis therapy. Patient data were randomly allocated to a modeling or testing set. The new index was developed in the modeling set. All indices were evaluated in the testing set. Results: We obtained data for 1,205 patients. Of the three existing indices, the Charlson index had the best discriminating features, with a concordance c statistic of 0.71. The addition of severity grading of several comorbid conditions did not improve discrimination. After combining the comorbidity indices with age, all c statistics improved. These final values ranged from 0.72 to 0.75. Conclusion: We conclude that the Khan, Davies, and Charlson scores are appropriate for expressing the prognostic impact of comorbidity on mortality risk in patients with ESRD provided sufficient adjustment for age is performed. Adding the severity grading of several comorbid conditions will not lead to improved prognostic power. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Patients

All new patients with ESRD from 35 Dutch dialysis centers were consecutively invited to participate in the Netherlands Co-operative Study on the Adequacy of Dialysis-2, a prospective cohort study. The aim of the study is to monitor the quality and adequacy of dialysis treatment in The Netherlands. All invited patients were 18 years or older, and chronic dialysis had to be their first renal replacement therapy. The inclusion period was January 1997 to November 2000.

Data collection procedures

Patient data were collected at

Results

We could include 1,205 patients. Their data were randomly allocated to one of two groups: data for 616 patients in the modeling set and the remaining 589 patients in the testing set. Both groups were highly similar with respect to patient characteristics (Table 1).

. Patient Characteristics of the Modeling and Testing Population

Empty Cell	Modeling Population (n = 616)	Testing Population (n = 589)
Age (y)	59.3 ± 15.1	59.1 ± 15.8
Men (%)	61	60
Primary kidney disease (%)
Diabetes	15	15
Glomerulonephritis	14	14
Renal

Discussion

In this prospective cohort study, we evaluated the prognostic power of four different comorbidity indices for patients with ESRD: the Khan, Davies, and Charlson indices and a new index designed to explicitly incorporate severity of comorbid conditions. Of the three existing indices, the Charlson index had the best discriminating features with respect to 2-year survival. Incorporating the severity of the respective comorbid condition did not improve discrimination. Including age led to a better

Acknowledgements

The authors thank A. Hart for statistical advice; the nursing staff of the dialysis centers, who collected most of the data, for their assistance; and J. Aurisch, A. Feller, A. Houweling, C. Janssen, B. Nijman, L. Ten Brinke, and K. Voss for assistance in the logistics of this study.

References (27)

SF Leavey et al.
Simple nutritional indicators as independent predictors of mortality in hemodialysis patients
Am J Kidney Dis
(1998)
AJ Collins et al.
Mortality risks of peritoneal dialysis and hemodialysis
Am J Kidney Dis
(1999)
KJ Jager et al.
What happens to patients starting dialysis in The Netherlands
Neth J Med
(2001)
EW Steyerberg et al.
Clinical trials in acute myocardial infarction: Should we adjust for baseline characteristics?
Am Heart J
(2000)
IH Khan et al.
Influence of coexisting disease on survival on renal replacement therapy
Lancet
(1993)
SJ Davies et al.
Comorbidity, urea kinetics, and appetite in continuous ambulatory peritoneal dialysis patients: Their interrelationship and prediction of survival
Am J Kidney Dis
(1995)
ME Charlson et al.
A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation
J Chronic Dis
(1987)
PE Watson et al.
Total body water volumes for adult males and females estimated from simple anthropometric measurements
Am J Clin Nutr
(1980)
J Bergstrom et al.
Protein and energy intake, nitrogen balance and nitrogen losses in patients treated with continuous ambulatory peritoneal dialysis
Kidney Int
(1993)
NP Mallick et al.
Hemodialysis
Lancet
(1999)

R Gokal et al.

Peritoneal dialysis

Lancet

(1999)

IH Khan

Comorbidity: The major challenge for survival and quality of life in end-stage renal disease

Nephrol Dial Transplant

(1998)

MD Wallen et al.

An analysis of cardiac mortality in patients with new-onset end-stage renal disease in New York State

Clin Nephrol

(2001)

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: For the Netherlands Co-operative Study on the Adequacy of Dialysis-2 (NECOSAD) study group: Apperloo AJ, Barendregt JNM, Birnie RJ, Boekhout M, Boer WH, van Bommel EFH, Büller HR, de Charro FTh, Doorenbos CJ, van Dorp WT, van Es A, Fagel WJ, Feith GW, Franssen CFM, Frenken LAM, van Geelen JACA, Geerlings W, Gerlag PGG, Gorgels JPMC, Grave W, Huisman RM, Jager KJ, Jansen MAM, Jie K, Koning-Mulder WAH, Koolen MI, Kremer Hovinga TK, Lavrijssen ATJ, Mulder AW, Parlevliet KJ, Rosman JB, van Saase JLCM, Schonk MJM, Schuurmans MMJ, Stevens P, Tijssen JGP, Valentijn RM, Vastenburg G, Verburg CA, Verhagen CE, Verstappen VMC, Vincent HH, Vos P.

: Supported in part by grant no. E.018 from The Dutch Kidney Foundation and grant no. OG97/005 from the Dutch National Health Insurance Board.

^★: Address reprint requests to Jeannette G. van Manen, PhD, AMC, Department of Clinical Epidemiology & Biostatistics, PO Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: [email protected]

^★★: 0272-6386/02/4001-0011$35.00/0

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Original Investigations: Dialysis TherapiesHow to adjust for comorbidity in survival studies in ESRD patients: A comparison of different indices★,★★

Abstract

Section snippets

Patients

Data collection procedures

Results

Discussion

Acknowledgements

Am J Kidney Dis

Am J Kidney Dis

Neth J Med

Am Heart J

Lancet

Am J Kidney Dis

J Chronic Dis

Am J Clin Nutr

Kidney Int

Lancet

Lancet

Comorbidity: The major challenge for survival and quality of life in end-stage renal disease

Nephrol Dial Transplant

An analysis of cardiac mortality in patients with new-onset end-stage renal disease in New York State

Clin Nephrol

Original Investigations: Dialysis Therapies
How to adjust for comorbidity in survival studies in ESRD patients: A comparison of different indices★,★★