Nihms 271845

NIH Public Access
Author Manuscript
Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.
Published in final edited form as:
NIH-PA Author Manuscript
Am J Kidney Dis. 2011 June ; 57(6): 894–902. doi:10.1053/j.ajkd.2010.12.023.
Predicting Mortality in Incident Dialysis Patients: An Analysis of

the United Kingdom Renal Registry
Martin Wagner, MD MS1,2, David Ansell, MD3, David M. Kent, MD MS4, John L. Griffith,
PhD5, David Naimark, MD6, Christoph Wanner, MD2, and Navdeep Tangri, MD1
1Department of Medicine, Division of Nephrology, Tufts Medical Center, Boston, MA, USA
2Department of Medicine I, Division of Nephrology, University Hospital Würzburg, Würzburg,

Germany
3UK Renal Registry, Southmead Hospital, Bristol, United Kingdom
4Center for Predictive Medicine Research, Institute for Clinical Research and Health Policy
Studies, Tufts Medical Center, Boston, MA, USA
5Design and Data Resource Center, Institute for Clinical Research and Health Policy Studies,
Tufts Medical Center, Boston, MA, USA
6Divisionof Nephrology, Sunnybrook Health Sciences Center and the Departments of Medicine
and of Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada
Abstract
Background—The risk of death in dialysis patients remains high, but varies significantly among
patients. No prediction tool is widely used in current clinical practice. We aimed to predict long-
term mortality in incident dialysis patients with easily obtainable variables.
Study Design—Prospective nationwide multicenter cohort study in the United Kingdom (UK
Renal Registry); Models were developed using Cox proportional hazards.
Setting and Participants—Patients initiating hemodialysis or peritoneal dialysis between 2002
and 2004, who survived at least three months on dialysis treatment, were followed for three years.
Analyses were restricted to subjects in whom information on comorbid conditions and laboratory
measurements were available (n=5447). The dataset was divided into datasets for model
development (n=3631, training) and validation (n=1816) by random selection.
Predictors—Basic patient characteristics, comorbidity and laboratory variables.

Outcomes—All cause mortality censored for kidney transplant, recovery of kidney function, and
loss to follow-up.
Results—In the training dataset, 1078 patients (29.7%) died within the observation period. The
final model of the training dataset included patient characteristics (age, race, primary kidney
© 2011 The National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Corresponding author: Martin Wagner, MD MS, Department of Medicine I, Division of Nephrology, Zentrum Innere Medizin,
Oberdürrbacher Strasse 6, 97080 Würzburg, Germany, Phone: +49 (931) 201-1, Fax: +49 (931) 201-639300, [email protected]
wuerzburg.de.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our
customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of
the resulting proof before it is published in its final citable form. Please note that during the production process errors may be
discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Financial Disclosure: The authors declare that they have no relevant financial interests.
Wagner et al. Page 2
disease, treatment modality), comorbidities (diabetes, history of cardiovascular disease, smoking)

and laboratory variables (hemoglobin, serum albumin, creatinine, calcium) and reached a C-
statistic of 0.75 (95% CI, 0.73–0.77) and could accurately discriminate between patients with low
(6%), intermediate (19%), high (33%) and very high (59%) mortality risk. The model was further
applied to the validation dataset and achieved a C-statistic of 0.73 (95% CI, 0.71–0.76).
Limitations—Number of missing comorbidity data and lack of an external validation dataset.
Conclusions—Basic patient characteristics, comorbidity and laboratory variables can predict
three-year mortality in incident dialysis patients with sufficient accuracy. Identification of
subgroups of patients according to mortality risk can guide future research and subsequently target
treatment decisions in individual patients.
Index Words
End stage renal disease; predictive model; mortality; hemodialysis; peritoneal dialysis
The risk of death in patients with end stage renal disease (ESRD) remains high 1, despite
advances in dialysis care 2. The primary cause of death is typically cardiovascular disease
(CVD), but infections and non-vascular sudden cardiac death also contribute significantly
3;4. Mortality risk varies considerably among ESRD patients, and it is dependent on
preexisting conditions and comorbidities such as diabetes, CVD, anemia, impairment of
bone mineral metabolism and chronic inflammation 5–7.
Several instruments have been developed to assess the burden of comorbid conditions and to
predict outcome in ESRD patients 8–15, reflecting the elevated risk when compared to the
general population 16. However, these approaches frequently ignore patient characteristics,
such as gender, race, primary kidney disease, treatment modality or important comorbidities
and none of these models is commonly used in clinical practice. Clinical experience may be
sufficient to classify the patients according to their mortality risk 17, but to make risk
assessment comparable and widely applicable, a more generalizable approach is needed. A
predictive model that can accurately stratify patients according to their risk for mortality
would be useful to assess the “case-mix” of renal centers and adjust for baseline risk in
comparative studies 2;18. Such a tool could further be employed to focus future research to
those patients likely to benefit from more or less intense treatment, thus providing the
evidence for clinical decision making.
The purpose of the current study was to develop a model predicting all cause mortality
within the first three years after starting dialysis in an unselected cohort of incident dialysis
patients in the United Kingdom who were still on dialysis treatment after three months since
inception. We aimed to include only readily available and easily obtainable patient
characteristics, comorbidities and basic laboratory variables.
Methods
Study Participants of the United Kingdom Renal Registry
The detailed organization of the United Kingdom Renal Registry (UKRR) has been
described previously 19. In brief, the UKRR is operated under the auspices of the UK Renal
Association and provides independent audit and analysis of renal care in the UK. Although
the UKRR now receives patient level data from all UK renal units, during the period of this
study, information was prospectively collected electronically from 60 renal units in England
and Wales at quarterly intervals for all patients receiving renal replacement therapy. Data
arriving at the UKRR are subjected to algorithms which identify suspicious values, which
are further verified and corrected if necessary by contacting the renal center.

The present analysis included all adult (≥18 yrs) incident dialysis patients who started
dialysis in 2002, 2003 and 2004 and who still received dialysis treatment three months after
inception. Thus, we excluded patients (n=1310) who died, underwent transplant or who
recovered kidney function within 90 days after initiation of dialysis (Figure 1). This reflects
the standard approach to investigate “true” ESRD patients amongst all those receiving
dialysis because the diagnosis of ESRD is commonly made after three months. Thus most of
the patients with dialysis-dependent acute kidney injury are excluded, but unfortunately,
ESRD patients who are at extremely high risk for death and die within the first three months
are not considered as well. Data on study subjects were available until December 31st 2007.
Patients were followed for at least three years.
Outcomes and variables of interest

The primary outcome “long-term mortality” represented all cause mortality within three
years after starting dialysis treatment. Covariates of interest comprised year of dialysis
initiation, age, gender, race, cause of ESRD, treatment modality (hemodialysis [HD] vs.
peritoneal dialysis [PD]) at three months after dialysis inception, change of treatment
modality within the first three months of treatment, and comorbidities. At initiation of
dialysis treatment, the UKRR collects information about diabetes, smoking status, and
history of CVD according to ischemic heart disease (angina, previous myocardial infarction,
coronary artery bypass graft or angioplasty), cerebrovascular disease and peripheral vascular
disease (claudication, ischemic or neuropathic ulcers, non coronary angioplasty, vascular
graft or aneurysm, amputation for peripheral vascular disease) 19. Socio-economic status
was assed by Townsend scores, which are based on postal codes, and range from least
deprived to most deprived (score 1 to 5) 20. In addition, hemoglobin, serum albumin,
calcium, phosphate, creatinine (predialysis) and ferritin were considered for the analyses.
We did not include body mass index (BMI), blood pressure, cholesterol and iPTH due to
missing data >20%. Anemia was defined as hemoglobin <12 g/dl in women and <13.5 g/dl
in men 21.
Since we considered comorbidities and laboratory variables as being essential for the
development of the prediction model, we excluded patients in whom none of the
comorbidity information was available (n=4859) or in whom laboratory data of the first six
months was missing (n=596) (Figure 1). Some renal centers reported comorbidity data more
frequently to the UKRR than other centers 22; therefore we investigated potential
differences in mortality risk between these renal units, but did not detect strong evidence for
center effects (data not shown).
The purpose of our prediction model was to assess the patient’s three-year mortality risk
after three months of dialysis treatment. Thus we used laboratory data that was obtained in
the second quarter of dialysis treatment. If this information was missing in patients who died
in the second quarter, we used laboratory measurements of the first quarter. At the start of
dialysis therapy, several impairments such as anemia, metabolic acidosis, hypervolemia and
hyperparathyreoidism may not be treated adequately. After three months of dialysis
treatment, these variables might be better controlled; however, with the variables available
in this dataset, specific impairments such as resistance to erythropoietin stimulating agents
cannot be identified. The final dataset was randomly split in a training dataset (2/3 of the
original cohort, n=3631) and a validation dataset (1/3 of the original cohort, n=1816) (Figure
1).
Statistical Methods
Cox proportional hazards models were used to model all cause mortality, censored for
transplant, recovery of kidney function (after 90 days) and loss to follow up. Age, gender

and treatment modality three months after dialysis initiation were forced in all analyses. We
included the continuous outcomes ferritin, albumin and calcium in their logarithmic forms.
The proportional hazards assumption was met by all variables as investigated with
Schoenfeld residuals. Outliers and influence points were identified by checking deviance
residuals and difference in betas (dfbetas). The performance of the models was assessed
with the time-dependent C-statistic 23. Similar to the area under the receiver operator curve,
it describes the probability that the model will assign the higher mortality risk to the patient
who actually died as compared to the patient who remained alive or was censored. Models
resulting from the training dataset were applied to the validation dataset with fixed Hazard
Ratios, i.e., the variables and their exact beta-coefficients were kept as developed for the
prediction model in the training dataset. To calibrate the model, mortality risk was split into
quartiles and observed versus predicted risk was investigated across risk strata 24. We chose
quartiles to reflect clinically useful categories of patients with low, intermediate, high and
very high risk, although a sufficient number of patients and outcomes were available to
investigate mortality risk across deciles, which is also commonly presented in the literature.
The analyses were performed on a complete case basis. We tested the robustness of our
model by (1) excluding patients who died in the second quarter and in whom laboratory
variables from the first quarter were used; (2) using laboratory data from quarter one rather
than from quarter two in all subjects; (3) imputing missing values by employing the Markov
Chain Monte Carlo method (SAS procedure proc mi) 25. We further investigated in
univariate and multivariate logistic regression models how patients with missing
comorbidity and laboratory information differed from those patients in whom this
information was available. All analyses were performed in SAS 9.1 (www.sas.com). The
analysis of this preexisting dataset was approved by the institutional review board at Tufts
Medical Center, Boston.
Results
Study population
Patient characteristics, comorbidities and laboratory data of study subjects in the training
and the validation dataset are displayed in table 1. Patients were predominantly male, the
median age was 64 yrs, and more than two third of the patients received hemodialysis three
months after dialysis inception. A third of the patients were diabetic or reported a history of
CVD. Approximately three quarters of the patients were classified as being anemic (79% in
training dataset and 73% in validation dataset).
Outcomes
In the training dataset, a total of 1078 patients (29.7%) died within the observation period
from day 90 until three years (Table 2), while 563 patients (15.5%) underwent transplant.
Half of the patients were alive and still on dialysis after three years. Only a few patients
were either lost to follow-up or recovered kidney function (approximately 1.5% each).
Similar results were observed in the validation dataset.
Predictors of Mortality
When only patient characteristics were included in the multivariate model (Table 3, model
1), older age, white race, diabetes as cause of ESRD and HD treatment (versus PD) were
independently associated with an increased risk for all cause mortality. In this analysis, a
change from HD to PD within the first three months of renal replacement therapy was
associated with a lower mortality risk as compared to a change from PD to HD. However,
this association did not achieve formal significance level (p=0.07) and was further diluted in
subsequent modeling. In a second step (model 2), the comorbidities diabetes, history of
CVD and smoking status were added and also independently associated with worse

outcome. The interaction term built by diabetes and CVD emerged as significant, indicating
a different effect of diabetes on mortality depending on whether or not the patient had a
history of CVD. Finally (model 3), the laboratory measures of hemoglobin, serum albumin,
creatinine and calcium appeared as predictors of mortality, after accounting for phosphate
and ferritin.
The accuracy of the Cox proportional hazards models was assessed by the C-statistic (Table
3). The model with basic patient characteristics already achieved considerable accuracy as
indicated by a C-statistic of 0.69 (95% confidence interval [CI], 0.67–0.71; model 1), which
further increased by adding comorbidity data and laboratory measurements (C-statistic,
0.75; 95% CI, 0.73–0.77]), mainly due to the latter.
To check the robustness of the model, we performed a number of sensitivity analyses. First,
we excluded patients who died in their second quarter of dialysis treatment and in whom
laboratory measurements from the first quarter were used rather than from quarter two. The
variables of the final model remained unchanged, and the hazard ratios were similar, as was
the C-statistic (0.74; 95% CI, 0.72–0.77). Second, when we used laboratory measurements
from quarter one in all patients of the training dataset, the model achieved a C-statistic of
0.72 (95% CI, 0.69–0.75) with all variables of the final model except race and hemoglobin.
Finally, since the described analyses were performed on the basis of complete cases, we
imputed all missing data. The hazard ratios of the complete case model were within the 95%
confidence limits of the hazard ratios derived from the imputation.
As mentioned, we excluded approximately 50% of the original cohort because of missing

comorbidity and laboratory data. These patients differed from patients in whom comorbidity
information was available; they had a higher three year mortality (38.6% vs. 29.7%), were
older, were more likely to be of white race and had an uncertain diagnosis of primary kidney
disease (all p<0.001). In multivariate logistic regression modeling aiming to identify risk
factors for comorbidity and laboratory data being missing, only race, primary kidney disease
and PD treatment emerged as independent predictors (detailed data not shown). We did not
impute missing comorbidity data on these patients. In order to confirm the validity of our
results in this population, we applied the multivariate prediction model with fixed hazard
ratios to these patients including only basic patient characteristics (model 1) which were
available and achieved similar discrimination (C-statistic 0.68; 95% CI, 0.65–0.71).
Calibration of the Model

We categorized patients in the training dataset according to their three-year mortality risk
into quartiles (Figure 2, panel A). The model could accurately discriminate between patients
with a low (6%), intermediate (19%), high (33%) and very high (59%) mortality risk. No
significant difference between observed and predicted mortality risk was found (p=0.9).
Validation of the model

When we applied the final model with fixed hazard ratios to the validation dataset, the
resulting C-statistic was 0.73 (95% CI, 0.7– 0.76). Observed and predicted mortality risk in
the validation dataset did not significantly differ (p=0.4) across risk strata: 7%, 20%, 34%,
and 59% in low, intermediate, high, and very high mortality risk, respectively (Figure 2,
panel B).
Discussion
In the UK Renal Registry database we developed a model that predicted three-year mortality
in patients who survived up to three months after dialysis inception and were still on dialysis
treatment. The model included exclusively easily obtainable and routinely collected patient

characteristics and laboratory variables. It achieved sufficient accuracy and was able to
discriminate accurately across risk strata.
It is a particular strength of this model that the underlying data were prospectively collected
on an incident cohort without any exclusion criteria. Data in the UKRR are considered of
good quality 26 and are representative for the UK and likely even for larger parts of
Europe19. We also included only variables which are routinely captured in the UK and
worldwide, making the model widely applicable to a variety of settings. Furthermore, we
judged the outcome three year all cause mortality – a very heterogeneous outcome with a
variety of underlying causes – as more important than short term mortality 9;12;15 or events
with less heterogeneity (e.g., CVD events 8), although these are frequently easier to predict.
There are only a few reports predicting long-term mortality in dialysis patients that
employed Cox models and provided data on model performance. Their results are in line
with our findings that patient characteristics, comorbidity data and basic laboratory variables
are important to predict mortality in long-term dialysis patients. Geddes et al. retrospectively
collected data about dialysis patients who died in 1997 from voluntarily participating renal
centers throughout Europe 10. Their analyses were thus based on patients who differed in
their time to death. Hence, patients who survived on dialysis or underwent transplant in the
same observation period were not included. Their model was further validated prospectively
in patients starting dialysis in the same renal centers and who were followed up to five years.
Unfortunately, the measures of accuracy provided, negative and positive predictive values,
ignore information on time to the event. The recently published index developed by Liu et
al. 11 used data from the United States Renal Data System (USRDS) to primarily assess the
prognostic value of comorbidities on mortality in incident dialysis patients who survived the
first 9 months on treatment. Patients undergoing transplant were excluded and laboratory
variables were not considered. Miskulin et al. described how a variety of comorbid
conditions impact on three-year mortality in prevalent dialysis patients of the US population
in the Dialysis Outcome and Practice Patterns Study (DOPPS) 14. Their final model reached
a C-statistic of 0.73 (95% CI, 0.72–0.74) and included patient characteristics, basic
laboratory variables, comorbidities (17 variables) and physical impairments (3 variables).
However, this model lacked routinely collected variables and could not be electronically
implemented into practice.
Although our model – as well as those from other groups – achieved considerable accuracy
and discrimination to classify patients according to their mortality risk, we suggest that the
results of this risk assessment should not (yet) be applied to individual patients in current
clinical practice. Therefore we refrained from transforming the model into an easy-to-use
score at this stage. While it seems intuitive that the model may provide clinically useful
information regarding a patient being classified as “low risk” (with a 6% three-year

mortality risk) as compared to a “very high risk patient” (with a mortality risk up to 60%),
any modulation of therapy and treatment decisions based on this classification lack
prospective clinical evidence. Once the validity of our prediction model was prospectively
proven to have an impact on modulating therapy and clinical outcomes, it can be
implemented in daily practice. Such a “risk-stratification-tool” could either be employed as a
clinical score or embedded in computer based management systems.
In our model we show that basic patient characteristics and laboratory markers are sufficient
to classify patients according to their mortality risk. These variables are not novel or
surprising, and in the last decade a variety of more specific factors, for example cardiac
function or biomarkers, such as CRP, adiponectin or NT-proBNP (N-terminal pro-brain
natriuretic peptide) 27–31, have been found to be associated with mortality in ESRD
patients. The challenge would be to test the markers regarding their incremental value on the

performance of our model, since the model already achieved good accuracy and
discrimination. In particular, it may be relevant to examine how many patients get correctly
(re-)classified by including versus ignoring the additional variables 32.
Furthermore, the model can form the basis for risk-stratified analyses of randomized
controlled trials (RCTs). Summary results of RCTs may reflect the treatment effect of a
relatively small subgroup of influential patients, and do not accurately describe the treatment
effect of the typical patient enrolled in the trial. While conventional subgroup analyses have
important limitations, risk-stratified analyses can frequently identify patients who
particularly benefit from a given treatment if there is considerable variation of baseline
risk33. Since the latter is certainly the case in the setting of dialysis, it is conceivable that an
analysis according to the patient’s mortality risk would provide clinical useful information.
Finally, the prediction model can be useful to evaluate the composition of patients treated in
a given center. Demographic and comorbidity features vary between facilities within certain
areas, which impact on mortality; this scenario is best described as variability in “case-mix”
2. Financial incentives to improve quality of care are increasingly considered in many health
care systems throughout the world 34. In the US, dialysis centers are evaluated by
performance and reimbursement is dependent on the “success” of the treatment of each
center (“pay for performance”) 35. A similar scenario is in discussion in the UK between the
NHS Information Centre, the NHS Healthcare Quality Improvement Programme (HQIP)
and the renal community. We hypothesize that our prognostic model could potentially be
used to create a “standardized mortality ratio” for UK renal units, making data between
centers more comparable to patients, health care providers, insurance companies and
researchers.
We are aware of several limitations of the current study. First, a priori to the modeling
process, we excluded a large number of patients in whom comorbidity and laboratory data
were not available. Although some of these variables were not missing completely at
random, we could not find center effects for missingness. Our basic model also validated
well in patients in whom these important data were missing. This finding suggests that the
differences in mortality rate may in fact be explained by the covariates in the model. We
therefore argue that the final model could be generalizable to the cohort with missing
comorbidity and laboratory data. As the amount of missing data decreases prospectively in
the UK, it is possible that the performance of our model may be further improved with the
addition of these variables. Second, certain parameters that may have improved the
performance of our model were not available, such as CRP-level, information on dialysis
access, dialysis dose or residual renal function; or due to a large number of missing data
(BMI, blood pressure, iPTH, cholesterol). Third, although we tested the robustness of our
model extensively and internally validated it in an independent subset of patients of the

UKRR, the results of our analyses need to be further externally validated in independent
datasets. For example, comorbidities such as CVD were listed as composites in the UKRR,
but may be available in a more detailed form in alternative datasets. It would be interesting,
how the combination and importance of variables holds in other settings. Finally, we
employed Cox proportional hazards models to predict all cause mortality. Although the
advantages of considering time to the event and including information on patients who
underwent transplant, recovered kidney function or were lost to follow-up as censored
events clearly outweigh the disadvantages of ignoring these patients, this approach assumes
that the patients who died post transplant had a similar risk of death as those not
transplanted, and may result in errors in model calibration. We achieved excellent
calibration but different censoring patterns in other dialysis populations may affect the
performance of the model.

Our model suggests that a limited number of basic patient characteristics and easily
obtainable and commonly measured variables are sufficient to predict with good accuracy
three-year mortality in patients who survived the first three months of dialysis treatment. We
would propose that novel biomarkers or other associations predicting mortality in long-term
dialysis patients should be added to and tested against our model to determine their
incremental value. Identification of subgroups of patients according to mortality risk can
guide future research that may be able to target treatment decisions in individual patients.
Acknowledgments
We thank the patients and the clinicians in the renal units who contributed data to the UK Renal Registry as well as
we thank Julie Gilg at the UK Renal Registry for administrative support. We thank Hocine Tighiouart for providing
the SAS macros for calculation of the C-statistic and model calibration in Cox proportional hazards models. We
also thank Andrew S. Levey and Bertram L. Kasiske for helpful discussions and critical revision of the manuscript.
Support: Dr Wagner receives funding from the fellowship training program of the National Kidney Foundation
Center for Clinical Practice Guideline Development and Implementation at Tufts Medical Center. Dr Kent is
supported by a grant of the National Institute of Health (NIH/NCRR 1UL1 RR025752). Dr Tangri is supported by
the KRESCENT postdoctoral fellowship award, a joint initiative of the Kidney Foundation of Canada, the Canadian
Institute of Health Research and the Canadian Society of Nephrology. The UK Renal Registry is funded by an
annual capitation charge to UK renal units and is independent of industry and government.
REFERENCES
1. Foley RN, Murray AM, Li S, et al. Chronic kidney disease and the risk for cardiovascular disease,
renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc
Nephrol. 2005; 16:489–495. [PubMed: 15590763]
2. Goodkin DA, Young EW, Kurokawa K, et al. Mortality among hemodialysis patients in Europe,
Japan, and the United States: case-mix effects. Am J Kidney Dis. 2004; 44:16–21. [PubMed:
15486869]
3. McDonald SP, Marshall MR, Johnson DW, et al. Relationship between dialysis modality and
mortality. J Am Soc Nephrol. 2009; 20:155–163. [PubMed: 19092128]
4. Sarnak MJ. Cardiovascular complications in chronic kidney disease. Am J Kidney Dis. 2003;
41:11–17. [PubMed: 12776309]
5. Block GA, Hulbert-Shearon TE, Levin NW, et al. Association of serum phosphorus and calcium ×
phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J
Kidney Dis. 1998; 31:607–617. [PubMed: 9531176]
6. Menon V, Wang X, Greene T, et al. Relationship between C-reactive protein, albumin, and
cardiovascular disease in patients with chronic kidney disease. Am J Kidney Dis. 2003; 42:44–52.
[PubMed: 12830455]
7. Weiner DE, Tighiouart H, Vlagopoulos PT, et al. Effects of anemia and left ventricular hypertrophy
on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol. 2005;
16:1803–1810. [PubMed: 15857925]

8. Adragao T, Pires A, Lucas C, et al. A simple vascular calcification score predicts cardiovascular risk
in haemodialysis patients. Nephrol Dial Transplant. 2004; 19:1480–1488. [PubMed: 15034154]
9. Barrett BJ, Parfrey PS, Morgan J, et al. Prediction of early death in end-stage renal disease patients
starting dialysis. Am J Kidney Dis. 1997; 29:214–222. [PubMed: 9016892]
10. Geddes CC, van Dijk PC, McArthur S, et al. The ERA-EDTA cohort study--comparison of
methods to predict survival on renal replacement therapy. Nephrol Dial Transplant. 2006; 21:945–
956. [PubMed: 16339161]
11. Liu J, Huang Z, Gilbertson DT, et al. An improved comorbidity index for outcome analyses among
dialysis patients. Kidney Int. 2010; 77:141–151. [PubMed: 19907414]
12. Mauri JM, Cleries M, Vela E. Design and validation of a model to predict early mortality in
haemodialysis patients. Nephrol Dial Transplant. 2008; 23:1690–1696. [PubMed: 18272779]

13. Merkus MP, Jager KJ, Dekker FW, et al. Predictors of poor outcome in chronic dialysis patients:
The Netherlands Cooperative Study on the Adequacy of Dialysis. The NECOSAD Study Group.
Am J Kidney Dis. 2000; 35:69–79. [PubMed: 10620547]
14. Miskulin D, Bragg-Gresham J, Gillespie BW, et al. Key comorbid conditions that are predictive of
survival among hemodialysis patients. Clin J Am Soc Nephrol. 2009; 4:1818–1826. [PubMed:
19808231]
15. Miskulin DC, Martin AA, Brown R, et al. Predicting 1 year mortality in an outpatient
haemodialysis population: a comparison of comorbidity instruments. Nephrol Dial Transplant.
2004; 19:413–420. [PubMed: 14736967]
16. Shah DS, Polkinghorne KR, Pellicano R, et al. Are traditional risk factors valid for assessing
cardiovascular risk in end-stage renal failure patients? Nephrology (Carlton). 2008; 13:667–671.
[PubMed: 18761627]
17. Moss AH, Ganjoo J, Sharma S, et al. Utility of the "surprise" question to identify dialysis patients
with high mortality. Clin J Am Soc Nephrol. 2008; 3:1379–1384. [PubMed: 18596118]
18. Miskulin DC, Meyer KB, Martin AA, et al. Comorbidity and its change predict survival in incident
dialysis patients. Am J Kidney Dis. 2003; 41:149–161. [PubMed: 12500232]
19. Ansell D. UK Renal Registry 11th Annual Report (December 2008). Nephron Clin Pract. 2009;
111 Suppl 1
20. Udayaraj UP, Ben-Shlomo Y, Roderick P, et al. Ethnicity, socioeconomic status, and attainment of
clinical practice guideline standards in dialysis patients in the United kingdom. Clin J Am Soc
Nephrol. 2009; 4:979–987. [PubMed: 19357243]
21. National Kidney Foudnation. KDOQI: II. Clinical practice guidelines and clinical practice
recommendations for anemia in chronic kidney disease in adults. Am J Kidney Dis. 2006; 47:S16–
S85. [PubMed: 16678661]
22. Udayaraj U, Tomson CR, Gilg J, et al. UK Renal Registry 11th Annual Report (December 2008):
Chapter 6 Comorbidities and current smoking status amongst patients starting renal replacement
therapy in England, Wales and Northern Ireland: national and centre-specific analyses. Nephron
Clin Pract. 2009; 111 Suppl 1:c97–c111. [PubMed: 19542707]
23. Mandel M, Galai N, Simchen E. Evaluating survival model performance: a graphical approach.
Stat Med. 2005; 24:1933–1945. [PubMed: 15806618]
24. Steyerberg EW, Eijkemans MJ, Harrell FE Jr, et al. Prognostic modeling with logistic regression
analysis: in search of a sensible strategy in small data sets. Med Decis Making. 2001; 21:45–56.
[PubMed: 11206946]
25. Schafer, JL. Analysis of Incomplete Multivariate Data. New York: Chapman and Hall; 1997.
26. Tangri N, Ansell D, Naimark D. Predicting technique survival in peritoneal dialysis patients:
comparing artificial neural networks and logistic regression. Nephrol Dial Transplant. 2008;
23:2972–2981. [PubMed: 18441002]
27. Drechsler C, Krane V, Winkler K, et al. Changes in adiponectin and the risk of sudden death,
stroke, myocardial infarction, and mortality in hemodialysis patients. Kidney Int. 2009; 76:567–
575. [PubMed: 19516245]
28. Eknoyan G, Beck GJ, Cheung AK, et al. Effect of dialysis dose and membrane flux in maintenance
hemodialysis. N Engl J Med. 2002; 347:2010–2019. [PubMed: 12490682]
29. Svensson M, Gorst-Rasmussen A, Schmidt EB, et al. NT-pro-BNP is an independent predictor of
mortality in patients with end-stage renal disease. Clin Nephrol. 2009; 71:380–386. [PubMed:
19356370]
30. Yamada S, Ishii H, Takahashi H, et al. Prognostic value of reduced left ventricular ejection fraction
at start of hemodialysis therapy on cardiovascular and all-cause mortality in end-stage renal
disease patients. Clin J Am Soc Nephrol. 2010; 5:1793–1798. [PubMed: 20595691]
31. Zimmermann J, Herrlinger S, Pruy A, et al. Inflammation enhances cardiovascular risk and
mortality in hemodialysis patients. Kidney Int. 1999; 55:648–658. [PubMed: 9987089]
32. Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, et al. Evaluating the added predictive ability of
a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;
27:157–172. [PubMed: 17569110]

33. Kent DM, Hayward RA. Limitations of applying summary results of clinical trials to individual
patients: the need for risk stratification. JAMA. 2007; 298:1209–1212. [PubMed: 17848656]
34. McDonald R, Harrison S, Checkland K, et al. Impact of financial incentives on clinical autonomy
and internal motivation in primary care: ethnographic study. BMJ. 2007; 334:1357. [PubMed:
17580318]
35. Rosenthal MB, Frank RG, Li Z, et al. Early experience with pay-for-performance: from concept to
practice. JAMA. 2005; 294:1788–1793. [PubMed: 16219882]

Figure 1. Study participants in the UK Renal Registry

Dataset for the analysis comprising patients in the UK Renal Registry initiating dialysis
between 2002 and 2004; exclusion of patients with events within the first 90 days, or
without information about comorbidities or laboratory data in the first 6 months of dialysis
treatment.

Figure 2. Three year mortality according to risk strata, calibration of the model
Observed (grey columns) and predicted (white columns) mortality risk within 3 years after
starting dialysis treatment in patients in the UK Renal Registry according to risk strata
derived from the final prediction model; panel A: training dataset, panel B: validation
dataset; * p-value between observed and predicted mortality risk.

Table 1
Characteristics of study subjects
training dataset validation dataset

(n=3631) (n= 1816)
age [yrs] 64 (49; 73) 64 (51; 74)
gender, male 62.2 59.7
BMI [kg/m2]1 25 (23; 29) 25 (22; 29)
treatment modality2
HD 70.1 72.3
PD 29.9 27.7
diastolic BP [mmHg]1,3 78±15 77±15
systolic BP [mmHg]1,3 144±26 144±26
Townsend score4
1 16.7 16.3
2 18.3 18.4
3 18.8 18.7
4 22.9 23.4
5 23.3 23.3
race category5
white 83.3 83.9
black 5.0 4.3
Asian 8.4 9.2
Chinese 0.7 0.6
other 2.6 2.1
cause of ESRD
diabetes 21.8 19.8
glomerulonephritis 10.5 12.1
polycystic kidney disease 7.1 7.1
pyelonephritis 8.5 8.1

renovascular disease 15.6 16.2
other 15.1 14.9
uncertain 21.4 21.8
comorbidity
diabetes6 29.1 27.5
CVD7 32.4 34.6
smoking 17.2 16.1
laboratory measurements
albumin [g/dL] 3.5 (3.2; 3.9) 3.5 (3.1; 3.9)
calcium [mg/dL] 9.6±0.9 9.6±0.9


(n=3631) (n= 1816)
phosphate [mg/dL] 5.1±1.7 5.0±1.6

iPTH [pg/mL]1 144 (60; 285) 148 (62; 303)
cholesterol [mg/dL]1 170 (143; 201) 174 (143; 205)
ferritin [ng/mL] 284 (164; 458) 292 (171; 472)
hemoglobin [g/dl] 11.3±1.8 11.3±1.8
SCr [mg/dL]3 7.2 (5.6; 9.2) 7.2 (5.5; 9.1)
Categorical data are given as percentage; continuous Data are means ± standard deviation or medians (25th; 75th percentile)
abbreviations: BMI, body mass index; PD, peritoneal dialysis; HD, hemodialysis; ESRD, end stage renal disease; CVD, cardiovascular disease;
iPTH, intact parathyroid hormone; BP, blood pressure; SCr, serum creatinine
conversion factors for units: serum creatinine in mg/dL to mol/L, ×88.4; cholesterol in mg/dL to mmol/L ×0.02586, albumin in g/dL to g/L ×10;
calcium in mg/dL to mmol/L ×0.2495; phosphorus in mg/dL to mmol/L ×0.3229; no conversion necessary for ferritin in ng/mL and ug/L, and
iPTH in pg/mL and ng/L
1
>20% missing data
2
Treatment modality after 3 months of dialysis treatment
3
Predialysis measurements
4
Socioeconomic status; least deprived (score 1), most deprived (score 5)
5
Self reported, patients of South Asian origin (i.e. excludes Chinese patients) are classified as “Asian”
6
Including diabetes as non primary cause of ESRD
7
Cardiovascular disease assessed according to a questionnaire about ischemic heart disease, cerebrovascular disease and peripheral vascular
disease

Table 2
Outcomes within 3 years of dialysis initiation

(n=3631) (n=1816)
death
Percentage reaching outcome 29.7 30.7
time to outcome [days] 508 (286; 772) 478 (258; 777)
transplant
recovery of kidney function

loss to follow-up

Times to outcome are medians (interquartile range).


NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Table 3
Mortality within 3 years of dialysis initiation, training dataset
model 11 model 21 model 32

(n=3232) (n=2815) (n=2388)
Wagner et al.
HR (95% CI) Wald χ2 HR (95% CI) Wald χ2 HR (95% CI) Wald χ2
Predictors of Mortality
age 1.04 (1.03–1.05) 177.6 1.04 (1.03–1.05) 152.5 1.04 (1.03–1.04) 99.3
gender, male 1.03 (0.89–1.18) 0.1 0.93 (0.80–1.08) 0.9 0.95 (0.80–1.12) 0.4
treatment modality3 1.25 (1.05–1.47) 6.5 1.19 (1.00–1.43) 3.1 1.32 (1.09–1.60) 8.3
race 18.8 14.5 9.9
black vs. white 0.47 (0.30–0.71) 0.49 (0.31–0.78) 0.50 (0.29–0.88)
Asiana vs. white 0.68 (0.51–0.90) 0.73 (0.54–0.99) 0.72 (0.50–1.03)
Chinese vs. white 0.72 (0.27–1.93) 0.39 (0.10–1.57) 0.45 (0.11–1.80)

other vs. white 1.01 (0.67–1.53) 1.10 (0.69–1.76) 0.80 (0.36–1.80)
cause of ESRD 75.7 66.9 50.3
GN vs.DM 0.36 (0.25–0.50) 0.50 (0.32–0.77) 0.48 (0.30–0.76)
PKD vs. DM 0.31 (0.20–0.48) 0.43 (0.25–0.72) 0.54 (0.31–0.96)
pyelonephritis vs. DM 0.59 (0.45–0.79) 0.78 (0.54–1.12) 0.94 (0.64–1.39)
RVD vs. DM 0.80 (0.65–0.98) 0.99 (0.74–1.34) 1.12 (0.81–1.54)
other vs. DM 1.07 (0.87–1.31) 1.62 (1.18–2.21) 1.72 (1.22–2.43)
uncertain vs. DM 0.72 (0.59–0.87) 0.98 (0.72–1.32) 1.18 (0.85–1.65)

DM4 -- -- -- 1.58 (1.18–2.11) 9.2 1.77 (1.28–2.44) 11.8
CVD5 -- -- -- 1.55 (1.29–1.86) 21.8 1.56 (1.28–1.90) 19.8
diabetes × CVD6 -- -- -- 0.67 (0.50–0.91) 6.8 0.61 (0.44–0.84) 9.0
smoking -- -- -- 1.41 (1.18–1.69) 14.0 1.38 (1.14–1.68) 11.1
hemoglobin [per 1-g/dl] -- -- -- -- -- -- 0.93 (0.89–0.98) 8.2
albumin [per log g/L] -- -- -- -- -- -- 0.14 (0.09–0.21) 95.9
SCr [per 1-mg/dL/] -- -- -- -- -- -- 0.96 (0.93–0.99) 4.1
calcium [per log mg/dL] -- -- -- -- -- -- 2.72 (1.13–6.58) 4.9

Page 16
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
model 11 model 21 model 32

(n=3232) (n=2815) (n=2388)
HR (95% CI) Wald χ2 HR (95% CI) Wald χ2 HR (95% CI) Wald χ2
Model Performance
Wagner et al.
C-statistic (95% CI) C-statistic (95% CI) C-statistic (95% CI)
Concordance 0.69 (0.67–0.71) 0.70 (0.68–0.72) 0.75 (0.73–0.77)
Variables age, gender and treatment modality forced in all multivariate Cox proportional hazards models;
abbreviations: HR, hazard ratio; CI, confidence interval; ESRD, end stage renal disease; GN, glomerulonephritis; PKD, polycystic kidney disease; RVD, renovascular disease; CVD, cardiovascular disease;
DM, diabetes mellitus; SCr, serum creatinine
1
Adjusted for start-year of dialysis, Townsend score, change in treatment modality within the first 3 months of dialysis treatment
2
Adjusted for start-year of dialysis, Townsend score, change in treatment modality within the first 3 months of dialysis treatment, phosphate, ferritin (log)
3
Treatment modality (hemodialysis vs. peritoneal dialysis) after 3 months of dialysis treatment
4
Including DM as non primary cause of ESRD
5
Cardiovascular disease assessed according to a questionnaire about ischemic heart disease, cerebrovascular disease and peripheral vascular disease
6
Interaction term of diabetes and CVD
a
“Asian” defined as patients of South Asian origin (i.e. excludes Chinese patients)

Page 17

Nihms 271845

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Nihms 271845

Uploaded by

Copyright:

Available Formats

NIH Public Access

Am J Kidney Dis. 2011 June ; 57(6): 894–902. doi:10.1053/j.ajkd.2010.12.023.

Predicting Mortality in Incident Dialysis Patients: An Analysis of

2Department of Medicine I, Division of Nephrology, University Hospital Würzburg, Würzburg,

Predictors—Basic patient characteristics, comorbidity and laboratory variables.

disease, treatment modality), comorbidities (diabetes, history of cardiovascular disease, smoking)

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

Outcomes and variables of interest

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

confidence limits of the hazard ratios derived from the imputation.

As mentioned, we excluded approximately 50% of the original cohort because of missing

Calibration of the Model

Validation of the model

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

information regarding a patient being classified as “low risk” (with a 6% three-year

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

model extensively and internally validated it in an independent subset of patients of the

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

16:1803–1810. [PubMed: 15857925]

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

Figure 1. Study participants in the UK Renal Registry

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

training dataset validation dataset

age [yrs] 64 (49; 73) 64 (51; 74)

gender, male 62.2 59.7

BMI [kg/m2]1 25 (23; 29) 25 (22; 29)

diastolic BP [mmHg]1,3 78±15 77±15

systolic BP [mmHg]1,3 144±26 144±26

white 83.3 83.9

black 5.0 4.3

Asian 8.4 9.2

Chinese 0.7 0.6

other 2.6 2.1

diabetes 21.8 19.8

glomerulonephritis 10.5 12.1

polycystic kidney disease 7.1 7.1

pyelonephritis 8.5 8.1

renovascular disease 15.6 16.2

other 15.1 14.9

uncertain 21.4 21.8

diabetes6 29.1 27.5

CVD7 32.4 34.6

smoking 17.2 16.1

albumin [g/dL] 3.5 (3.2; 3.9) 3.5 (3.1; 3.9)

calcium [mg/dL] 9.6±0.9 9.6±0.9

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

training dataset validation dataset

phosphate [mg/dL] 5.1±1.7 5.0±1.6

iPTH [pg/mL]1 144 (60; 285) 148 (62; 303)

cholesterol [mg/dL]1 170 (143; 201) 174 (143; 205)

ferritin [ng/mL] 284 (164; 458) 292 (171; 472)

hemoglobin [g/dl] 11.3±1.8 11.3±1.8

SCr [mg/dL]3 7.2 (5.6; 9.2) 7.2 (5.5; 9.1)

Am J Kidney Dis. Author manuscript; available in PMC 2012 June 1.

training dataset validation dataset

Percentage reaching outcome 29.7 30.7

time to outcome [days] 508 (286; 772) 478 (258; 777)

Percentage reaching outcome 15.5 13.6

time to outcome [days] 553 (345; 816) 501 (313; 721)