- Email: [email protected]
Prevalence and Associated Comorbidities of Moderate to Severe Chronic Renal Impairment in Chinese Nursing Home Older Adults
JAMDA 13 (2012) 630e633
JAMDA journal homepage: www.jamda.com
Original Study
Prevalence and Associated Comorbidities of Moderate to Severe Chronic Renal Impairment in Chinese Nursing Home Older Adults Tuen Ching Chan MBBS, FHKCP a, b, *, D.Y.H. Yap MBBS, FHKCP c, Y.F. Shea MBBS, MRCP a, b, K.H. Luk MBBS, FRCP a, H.W. Chan MB Bch, FRCP a, L.W. Chu MD, FRCP b a
Department of Medicine and Geriatrics, Fung Yiu King Hospital, 9 Sandy Bay Road, Pokfulam, Hong Kong SAR, China The University of Hong Kong, Division of Geriatrics, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China c The University of Hong Kong, Division of Nephrology, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China b
a b s t r a c t Keywords: Nursing home older adults renal impairment renal failure prevalence Chinese
Objective: To investigate the prevalence and associated comorbidities of Stage 3 (GFR 30e59 mL/min/ 1.73m2) and Stages 4 and 5 (GFR <30 mL/min/1.73m2) chronic kidney disease (CKD) among Chinese nursing home older adults. Design: Retrospective cross-sectional study. Glomerular filtration rate (GFR) was estimated by Modification of Diet in Renal Disease Study (Chinese-adjusted) equation and The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Setting: Nine nursing homes in Hong Kong Participants: Participants included 812 nursing home older adults (271 men and 571 women), mean age 86.0 7.6. Measurements: Prevalence of Stage 3 (GFR 30e59 mL/min/1.73m2) and Stages 4 and 5 (GFR <30 mL/min/ 1.73m2) CKD. The comorbidities associated with renal impairment were also assessed. Results: There were 18.4% of nursing home older adults who had elevated serum creatinine levels above the normal limits. Using Modification of Diet in Renal Disease Study and CKD-EPI equations, 26.4% and 21.2% of them had Stage 3 CKD, whereas 6.8% and 4.4% had Stage 4e5 CKD, respectively. Diabetes mellitus, hypertension, congestive heart failure, and ischemic heart disease correlated significantly with moderate to severe renal impairment in Chinese nursing home older adults. Conclusion: Stages 3 to 5 CKD are prevalent in Chinese nursing home older adults. Early identification of these patients facilitates drug prescription, renal management, and advance care planning. Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc.
Older adults are prone to develop chronic renal insufficiency as advancing age and multiple comorbidities contribute to kidney dysfunction.1 In this context, assessment of renal function is relevant in older adults, as renal impairment may affect dosage adjustment for medication prescription, dietary modifications, anticipation of associated comorbidities, preparation for dialysis, and planning of end-of-life care.2 Unfortunately, renal function estimation by serum creatinine level alone can be misleading in older adults3 and hence there is increasing popularity to use the Modification of Diet in Renal Disease equation (MDRD)4 and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to assess renal function.5 Renal impairment was prevalent in Caucasian communitydwelling older adults. Stengel et al6 reported a prevalence of up to 15% of older adults had Stage 3 to 5 CKD. Among Caucasian nursing The authors declare no conflicts of interest. * Address correspondence to Tuen Ching Chan, MBBS, FHKCP, The University of Hong Kong, Division of Geriatrics, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China. E-mail address: [email protected] (T.C. Chan).
home older adults, approximately 4% had Stage 4e5 CKD (glomerular filtration rate [GFR] <30 mL/min/1.73m2).7 To our knowledge, there was no published data regarding the prevalence of Stage 3 (GFR 30e59 mL/min/1.73m2) and Stage 4e5 (GFR <30 mL/min/1.73m2) chronic kidney disease (CKD) in Chinese nursing home older adults. The aim of the present study was to examine the prevalence and the comorbidities associated with Stages 3 to 5 CKD among Chinese nursing home older adults. Methods This was a retrospective cross-sectional study conducted in Chinese nursing homes in the Hong Kong West Cluster (HKWC) in June 2009. HKWC is 1 of the 7 major health districts in Hong Kong and accommodates more than 6000 older adults in more than 70 nursing homes. In Hong Kong, nursing homes are broadly categorized into those privately owned (private homes) and those operated by charitable nonprofit making organizations (C&A nursing home). C&A nursing homes are required to follow a standard staff-to-residents ratio, with
1525-8610/$ - see front matter Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc. doi:10.1016/j.jamda.2012.05.007
T.C. Chan et al. / JAMDA 13 (2012) 630e633
comparable facility and quality of care.8 Adults aged 65 or older living in the 9 C&A nursing homes in HKWC were included for analysis. Outreach clinical services for the nursing home older adults were provided by the geriatricians of the Hong Kong West (HKW) Community Geriatric Assessment Team (CGAT). Regular health assessment was offered to the nursing home residents, which included annual blood test on renal function (ie, serum sodium, potassium, chloride, urea, and serum creatinine levels).9 Clinical data within 6 months of the study were retrieved from Hong Kong Hospital Authority Computer Management System (CMS). The subjects were categorized into 1 of the following age groups: 70 years or younger, 71 to 80, 81 to 89 and 90 years and older. The number and type of comorbidity were quantified using the Charlson Co-morbidity Index (CCI), which was validated for the use in clinical research.10e13 In our center, serum creatinine levels were measured using the modified kinetic Jaffe assay (Roche Modular DDP Analyzer, Indianapolis, IN), with a laboratory coefficient of variation less than 1%. The adult serum creatinine references reported by our laboratory were 67 to 109 mmol/L in men and 49 to 82 mmol/L in women, respectively. In this study, the GFR was estimated by the MDRD and CKD-EPI equations (listed as follows). MDRD Chinese adjusted equation4
GFR ml=min=1:73m2
¼ 175 ðPCr Þ
1:234
0:179
ðageÞ
0:79 ðif femaleÞ PCr ¼ plasma creatinine concentration in mg/dL CKD-EPI5
GFR ml=min=1:73m2
¼ 141 minðPCr Þa maxðPCr Þ1:209 0:993Age 1:018 ðif femaleÞ
PCr ¼ plasma creatinine concentration in mg/dL a ¼ e0.329 for females and e0.411 for males, min indicates minimum of PCr, and max indicates the maximum of PCr. Patients were stratified to Stage 3 (30e59 mL/min/1.73m2) or Stage 4e5 (<30 mL/min/1.73m2) CKD according to the modified version of Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. The study was approved by the institutional review boards at the University of Hong Kong and Hospital Authority. Statistical Analysis Continuous valuables were expressed as mean SD of the mean (mean SD). Chi-square test was used to compare categorical variables and the correlations were assessed by Cramer’s Phi test (4c). Spearman’s rank correlation coefficient (r) was used to assess the correlation between (1) age and creatinine, and (2) age and GFR estimated by MDRD and CKD-EPI. Kendall tau rank correlation coefficient (s) was used to assess the correlation between age group and severity of renal impairment estimated by MDRD and CKD-EPI. Statistical significance was inferred by a 2-tailed P value of .05 or less. All statistical analyses were performed by Statistical Package for Social Science (Windows version 18; SPSS Inc, Chicago, IL). Results A total of 812 older adults were included for analysis and their clinical characteristics are summarized in Table 1. The mean age was 86.0 7.6 with a mean Charlson’s score of 2.85 1.5. The mean creatinine level was 96.4 50.7 mmol/L. The mean GFR was 75.1 31.7 mL/min/1.73m2 by MDRD and 76.5 24.0 mL/min/1.73m2 by CKD-EPI. GFR estimated by MDRD or CKD-EPI equations decreased with increasing age (for MDRD: r ¼ e0.08, P < .001; for CKD-EPI:
631
Table 1 Clinical Characteristics of 812 Chinese Nursing Home Older Adults
Age, mean SD <70, n (%) 71e80, n (%) 81e90, n (%) >91, n (%) Charlson Comorbidity Index, mean SD Hypertension, n (%) Diabetes, n (%) Arrhythmia, n (%) Congestive heart failure, n (%) Peripheral vascular disease, n (%) Chronic obstructive pulmonary disease, n (%) Cerebrovascular disease, n (%) Creatinine, mmol/L, mean SD MDRD-GFR, mL/min/1.73m2, mean SD CKD-EPI-GFR, mL/min/1.73m2, mean SD
Male (n ¼ 271)
Female (n ¼ 541)
Overall (n ¼ 812)
83.8 7.6 12 (4.4) 79 (29.2) 124 (45.8) 56 (20.7) 2.83 1.54
87.1 7.4 9 (1.7) 90 (16.6) 267 (49.4) 175 (32.3) 2.87 1.49
86.0 7.6 21 (2.6) 169 (20.8) 391 (48.2) 231 (28.4) 2.85 1.5
168 84 26 37 9 37
348 139 62 95 22 43
516 223 88 132 31 80
(62) (31.0) (9.6) (13.7) (3.3) (13.7)
(64.3) (25.7) (11.5) (17.6) (4.1) (7.9)
(63.5) (27.5) (10.8) (16.3) (3.8) (9.9)
63 (23.3) 101.7 44.5 78.3 30.1
102 (18.8) 93.7 53.4 73.5 32.4
165 (20.3) 96.4 50.7 75.1 31.7
69.9 19.7
79.8 25.2
76.5 24.0
CKD-EPI-GFR, glomerular filtration rate by The Chronic Kidney Disease Epidemiology Collaboration equation; MDRD-GFR, glomerular filtration rate by Modification of Diet in Renal Disease equation.
r ¼ e0.14, P < .001) but serum creatinine level did not correlate with age (r ¼ e0.018, P ¼ .56). Using the MDRD and CKD-EPI equations, 26.4% and 21.2% of older adults had Stage 3 whereas 6.8% and 4.4% had Stage 4e5 CKD respectively (Table 2). With the MDRD equation, the prevalence of Stage 3 or Stage 4e5 CKD were 21.4% and 4.8%, 23.8% and 5.4 %, 27.3% and 7.7% as well as 29.6% and 8.5% for patients aged younger than 70, 71 to 80, 81 to 90, and 91 or older, respectively. With the CKD-EPI equation, the prevalence of Stage 3 and Stage 4e5 CKD were 14.3% and 0%, 16.6% and 3.6 %, 22.3% and 4.3%, and 23.4% and 5.6% for patients aged younger than 70, 71 to 80, 81 to 90, and 91 or older, respectively. The prevalence of Stage 3e5 CKD estimated by the MDRD or CKD-EPI equations increased with age group (For MDRD: s ¼ 0.08; P < .01; for CKD-EPI: s ¼ 0.13; P < .001) (Figure 1), whereas the prevalence of abnormal serum creatinine levels did not correlate with age group (s ¼ 0.02, P ¼ .56). Using the MDRD equation to estimate the GFR, the following factors significantly correlated with Stage 3e5 CKD (ie, GFR< 60 mL/ min/1.73m2): diabetes mellitus (DM) (4c ¼ 0.19; P < .001), hypertension (HT) (4c ¼ 0.13; P < .001), congestive heart failure (CHF) (4c ¼ 0.16; P < .001), and ischemic heart disease (IHD) (4c ¼ 0.09; P < .01). Similarly, these 4 factors significantly correlated with Stages 3 to 5 CKD in Chinese nursing home residents with calculations based on the CKD-EPI equations. When further stratified to Stage 3 (GFR 30e59 mL/min/1.73m2) or Stage 4e5 (<30 mL/min/1.73m2) CKD, DM, HT, Table 2 Prevalence of Moderate and Severe Renal Impairment in 812 Chinese Nursing Home Older Adults
MDRD-GFR 30e59c (n ¼ 214) <30 (n ¼ 55) CKD-EPI-GFR 30e59 (n ¼ 172) <30 (n ¼ 36) Serum creatinine Above laboratory reference limit (n ¼ 150)
Male (n ¼ 271), n (%)
Female (n ¼ 541), n (%)
Overall (n ¼ 812), %
65 (24.0) 10 (3.7)
149 (27.5) 45 (8.3)
26.4 6.8
68 (25.1) 12 (4.4)
104 (19.2) 24 (4.4)
21.2 4.4
44 (16.2)
106 (19.6)
18.4
Units are in mL/min/1.73m2. CKD-EPI-GFR, glomerular filtration rate by The Chronic Kidney Disease Epidemiology Collaboration equation; MDRD-GFR, glomerular filtration rate by Modification of Diet in Renal Disease equation.
632
T.C. Chan et al. / JAMDA 13 (2012) 630e633
Age
Age
>59 MDRD-GFR
<70
71-80
81-90
>91
73.8
70.8
65
61.9
71-80
81-90
>91
>59
85.7
79.9
73.4
71
30-59
14.3
16.5
22.3
23.4
<30
0
3.6
4.3
5.6
de
CKD-EPI-GFR
bc 2
<70
30-59
21.4
23.8
27.3
29.6
<30
4.8
5.4
7.7
8.5
(ml/min/1.73m )
(ml/min/1.73m2)
a. Correlated by Kendall tau rank correlation coefficient ( ) b. MDRD-GFR: Glomerular filtration rate by Modification of Diet in Renal Disease equation c. Kendall tau rank correlation coefficient ( ) =0.08; p<0.01 d. CKD-EPI-GFR: Glomerular filtration rate by The Chronic Kidney Disease Epidemiology Collaboration equation e.
=0.13; 0<0.001
Fig. 1. Prevalence of moderate or severe renal impairment in different age groups.*
CHF, and IHD remained to correlate with these 2 severities of renal impairment respectively (Table 3). Discussion To our knowledge, this was the first study that examined the prevalence of renal impairment among Chinese nursing home older adults. In the present study, 33.2% and 25.6% had Stages 3 to 5 CKD estimated by the MDRD and CKD-EPI equations, respectively. In this study, the prevalence of renal impairment determined by estimated GFR using the MDRD or CKD-EPI equations was much higher than the prevalence of 18.4% by elevated serum creatinine levels. Although serum creatinine is a more convenient method to assess renal impairment, its level is affected by multiple factors, including muscle mass, dietary protein intake, and renal tubular secretion.14 With aging, the decline in muscle mass may mask the increase in serum creatinine level expected with a decline in renal function and such discrepancy is even more significant among nursing home elderly.15e17 Hence, identification of older adults with renal impairment by the MDRD or CKD-EPI equations would be more preferable to prevent inappropriate prescriptions and dosage adjustments.18 Compared with the MDRD equations, the prevalence of Stage 3 or Stage 4 and 5 CKD were both lower when estimation of GFR was done
by the CKD-EPI equation (Stage 3 CKD: MDRD 26.4% vs CKD-EPI 21.2%; Stage 4e5 CKD: MDRD 6.8% vs CKD-EPI 4.4%). This discrepancy might be accounted for by the intrinsic difference between the 2 equations; however, the MDRD equation may appear to be more reliable in this setting because this equation was validated previously in Chinese adults whereas the CKD-EPI did not have such validation. In this study, Table 3 Comorbidities That Correlate Significantly With Moderate or Severe Renal Impairment in Chinese Nursing Home Older Adults MDRD-GFR
DM HT CHF IHD
CKD-EPI-GFR
<60
30e59
<30
<60
30e59
<30
0.19z 0.13z 0.16z 0.09y
0.16z 0.13z 0.13z 0.07*
0.19z 0.07* 0.16z 0.11y
0.17z 0.09y 0.13z 0.10y
0.14z 0.10y 0.12z 0.10y
0.15z 0.04* 0.10* 0.05*
Significance was assessed by chi-square test and the correlation coefficient was assessed Cramer’s Phi test (4c). Units are in mL/min/1.73m2. CHF, congestive heart failure; CKD-EPI-GFR, glomerular filtration rate by The Chronic Kidney Disease Epidemiology Collaboration equation; DM, diabetes mellitus; HT, hypertension; IHD, ischemic heart disease; MDRD-GFR, glomerular filtration rate by Modification of Diet in Renal Disease equation. *P < .05. y P < .01. z P < .001.
T.C. Chan et al. / JAMDA 13 (2012) 630e633
we did not estimate GFR with the Cockcroft-Gault (CG) equation, although this is another commonly used and well-validated equation for estimating GFR.19 The CG equation was derived from Caucasians and had not been validated in Chinese. Therefore, the use of a Chinese-validated MDRD equation may be more appropriate than the CG equation to estimate GFR in our study. As shown in previous studies, the use of the CG equation may be associated with more underestimation of reduced GFR when compared with the MDRD and CKD-EPI equations,20,21 although a definitive conclusion cannot be drawn from our data because we had not applied the CG equation in our study. Currently, the CG equation is the standard for dose adjustment of medications in the face of renal impairment. 22 Although both the MDRD and CG equations may be misleading in the very old, one should appreciate that the package inserts of most prescription drugs use the CG equation to determine dosages, and errors may be introduced by applying the MDRD equation for dosage adjustment. In this regard, it would be desirable to also include dosage adjustment according to MDRD equation in the package inserts.23 Our data suggested that DM, HT, CHF, and IHD correlate significantly with renal impairment in Chinese nursing home older adults. Although a causal-relationship cannot be drawn from this crosssectional analysis, we believe that it is still worthwhile to regularly monitor for renal disease among nursing home older adults presented with these comorbidities. This approach might detect early kidney dysfunction and offer timely management for these patients. Furthermore, optimal management of these comorbidities and renal impairment may reduce mortality.24 Angiotensin-converting enzyme inhibitor can be used in these older adults to retard renal deterioration.25,26 Aspirin and statin should be considered to reduce the cardiovascular risk.27,28 In addition, the early identification of older adults with stage 4e5 CKD also facilitates advance care planning including preparation for dialysis or palliative renal care.29,30 There were several limitations in this study. First, we used MDRD and CKD-EPI equations, which may overestimate or underestimate GFR. The accuracy of creatinine clearance measurement can be improved with 24-hour urine collection, but such approach is costly, cumbersome, and may not be feasible in many nursing home older adults because of their functional limitation (eg, urinary incontinence). Instead, we believe that GFR estimation by MDRD or CKD-EPI provides a good alternative that is practical and feasible. Second, the CCI was quantified based on the ICD-9-CM coding in CMS but there is always undercoding in real clinical practice. Add to that, the variability in disease severity may not be adequately captured by the ICD9-CM coding. Third, this study was conducted among the C&A nursing homes in the HKWC, where the conditions might be different from private nursing homes and nursing homes in other districts. Such shortcomings might limit the generalizability of our result. However, our study has included a good number of patients from different nursing homes in the HKWC and hence we believe that our data closely resemble the realistic clinical situation among the Chinese nursing home older adults. Conclusion Stages 3 to 5 CKD are prevalent in Chinese nursing home older adults. Early identification of these patients allows timely management of their renal conditions, appropriate drug prescription, and dosage adjustment as well as optimal advance care planning. Acknowledgment The authors thank Dr Matthew C. W. Yeung, Department of Biochemistry, Queen Mary Hospital, Hong Kong, for providing method of serum creatinine level measurements in the Queen Mary Hospital.
633
References 1. Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985;33:278e285. 2. National Kidney Foundation. Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:1e266. 3. Wong NA, Jones HW. An analysis of discharge drug prescribing amongst elderly patients with renal impairment. Postgrad Med J 1998;74:420e422. 4. Ma YC, Zuo L, Chen JH, et al. Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 2006;17:2937e2944. 5. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604e612. 6. Stengel B, Metzger M, Froissart M, et al. Epidemiology and prognostic significance of chronic kidney disease in the elderly: The three city prospective cohort study. Nephrol Dial Transplant 2011;26:3286e3295. 7. Garg AX, Papaioannou A, Ferko N, et al. Estimating the prevalence of renal insufficiency in seniors requiring long-term care. Kidney International 2004; 65:649e653. 8. Tang M, Woo J, Hui E, et al. Utilization of emergency room and hospitalization by Chinese nursing home residents. A cross-sectional study. J Am Med Dir Assoc 2010;11:325e332. 9. Luk JKH, Pau MML, Chan FHW, Yu C. Outreach geriatric private nursing home service in Hong Kong Central and Western cluster. JHK Geriatr Soc 2002;11: 5e10. 10. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 1987;40:373e383. 11. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative database. J Clin Epidemiol 1992;45:613e619. 12. Groot V, Beckerman H, Lankhorst GJ, et al. How to measure comorbidity: A critical review of available methods. J Clin Epidemiol 2003;56:221e229. 13. Schneeweiss S, Maclure M. Use of comorbidity scores for control of confounding in studies using administrative databases. Int J Epidemiol 2000;29: 891e898. 14. Hsu CY, Chertow GM, Curhan GC, et al. Methodological issues in studying the epidemiology of mild to moderate chronic renal insufficiency. Kidney Int 2002; 13:2812e2816. 15. Puyol DR. The aging kidney. Kidney Int 1998;54:2247e2265. 16. Epstein M. Aging and the kidney. J Am Soc Nephrol 1996;7:1106e1122. 17. Salive ME, Jones CA, Guralnik JM, et al. Serum creatinine levels in older adults: Relationship with health status and medications. Age Aging 1995;24: 142e150. 18. Corsonello A, Pedone C, Lattanzio F, et al. Association between glomerular filtration rate and adverse drug reactions in elderly hospitalized patients: The role of the estimating equation. Drugs Aging 2011;28:379e390. 19. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31e41. 20. Nicoll SR, Sainsbury R, Bailey RR, et al. Assessment of creatinine clearance in healthy subjects over 65 years of age. Nephron 1991;59:621e625. 21. Dharmarajan TS, Yoo J, Russell RO, et al. Chronic kidney disease staging in nursing home and community older adults: Does the choice of Cockcroft-Gault, Modification of Diet in Renal Disease Study, or the Chronic Kidney Disease Epidemiology Collaboration Initiative Equations matter? J Am Med Dir Assoc 2012;13:151e155. 22. Food and Drug Administration. Guidance for industry: Pharmacokinetics in patients with impaired renal function; study design, data analysis, and impact on dosing and labeling. US Department of Health and Human Services; 1998. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfor mation/Guidances/ucm072127.pdf, accessed May 30, 2012. 23. Stevens LA, Nolin TD, Richardson MM, et al. Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations. Am J Kidney Dis 2009;54:33e42. 24. Feldman SM, Rosen R, Destasio J. Status of diabetes management in nursing home setting in 2008: A retrospective chart review and epidemiology study of diabetic nursing home residents and nursing home initiatives in diabetes management. J Am Med Dir Assoc 2009;10:354e360. 25. Ahmed A, Kiefe CL, Allman RM, et al. Survival benefits of angiotensin converting enzyme inhibitors in older heart failure patients with perceived contraindications. J Am Geriatr Soc 2002;50:1659e1666. 26. Mann JFE, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: The HOPE randomized trial. Ann Intern Med 2001;134:629e636. 27. Levy CR, Radcliff TA, Williams ET, et al. Acute myocardial infarction in nursing home residents: Adherence to treatment guidelines reduces mortality, but why is adherence so low? J Am Med Dir Assoc 2009;10:56e61. 28. Parikh S, Shrank WH, Mogun H, et al. Statin utilization in nursing home patients after cardiac hospitalization. J Gen Intern Med 2010;12:1293e1299. 29. Chu LW, Luk JK, Hui E, et al. Advance directive and end-of-life care preferences among Chinese nursing home residents in Hong Kong. J Am Med Dir Assoc 2011;12:143e152. 30. Yu AW, Chau KF, Ho YW, et al. Development of the “peritoneal dialysis first” model in Hong Kong. Perit Dial Int 2007;27:53e55.
JAMDA journal homepage: www.jamda.com
Original Study
Prevalence and Associated Comorbidities of Moderate to Severe Chronic Renal Impairment in Chinese Nursing Home Older Adults Tuen Ching Chan MBBS, FHKCP a, b, *, D.Y.H. Yap MBBS, FHKCP c, Y.F. Shea MBBS, MRCP a, b, K.H. Luk MBBS, FRCP a, H.W. Chan MB Bch, FRCP a, L.W. Chu MD, FRCP b a
Department of Medicine and Geriatrics, Fung Yiu King Hospital, 9 Sandy Bay Road, Pokfulam, Hong Kong SAR, China The University of Hong Kong, Division of Geriatrics, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China c The University of Hong Kong, Division of Nephrology, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China b
a b s t r a c t Keywords: Nursing home older adults renal impairment renal failure prevalence Chinese
Objective: To investigate the prevalence and associated comorbidities of Stage 3 (GFR 30e59 mL/min/ 1.73m2) and Stages 4 and 5 (GFR <30 mL/min/1.73m2) chronic kidney disease (CKD) among Chinese nursing home older adults. Design: Retrospective cross-sectional study. Glomerular filtration rate (GFR) was estimated by Modification of Diet in Renal Disease Study (Chinese-adjusted) equation and The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Setting: Nine nursing homes in Hong Kong Participants: Participants included 812 nursing home older adults (271 men and 571 women), mean age 86.0 7.6. Measurements: Prevalence of Stage 3 (GFR 30e59 mL/min/1.73m2) and Stages 4 and 5 (GFR <30 mL/min/ 1.73m2) CKD. The comorbidities associated with renal impairment were also assessed. Results: There were 18.4% of nursing home older adults who had elevated serum creatinine levels above the normal limits. Using Modification of Diet in Renal Disease Study and CKD-EPI equations, 26.4% and 21.2% of them had Stage 3 CKD, whereas 6.8% and 4.4% had Stage 4e5 CKD, respectively. Diabetes mellitus, hypertension, congestive heart failure, and ischemic heart disease correlated significantly with moderate to severe renal impairment in Chinese nursing home older adults. Conclusion: Stages 3 to 5 CKD are prevalent in Chinese nursing home older adults. Early identification of these patients facilitates drug prescription, renal management, and advance care planning. Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc.
Older adults are prone to develop chronic renal insufficiency as advancing age and multiple comorbidities contribute to kidney dysfunction.1 In this context, assessment of renal function is relevant in older adults, as renal impairment may affect dosage adjustment for medication prescription, dietary modifications, anticipation of associated comorbidities, preparation for dialysis, and planning of end-of-life care.2 Unfortunately, renal function estimation by serum creatinine level alone can be misleading in older adults3 and hence there is increasing popularity to use the Modification of Diet in Renal Disease equation (MDRD)4 and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to assess renal function.5 Renal impairment was prevalent in Caucasian communitydwelling older adults. Stengel et al6 reported a prevalence of up to 15% of older adults had Stage 3 to 5 CKD. Among Caucasian nursing The authors declare no conflicts of interest. * Address correspondence to Tuen Ching Chan, MBBS, FHKCP, The University of Hong Kong, Division of Geriatrics, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China. E-mail address: [email protected] (T.C. Chan).
home older adults, approximately 4% had Stage 4e5 CKD (glomerular filtration rate [GFR] <30 mL/min/1.73m2).7 To our knowledge, there was no published data regarding the prevalence of Stage 3 (GFR 30e59 mL/min/1.73m2) and Stage 4e5 (GFR <30 mL/min/1.73m2) chronic kidney disease (CKD) in Chinese nursing home older adults. The aim of the present study was to examine the prevalence and the comorbidities associated with Stages 3 to 5 CKD among Chinese nursing home older adults. Methods This was a retrospective cross-sectional study conducted in Chinese nursing homes in the Hong Kong West Cluster (HKWC) in June 2009. HKWC is 1 of the 7 major health districts in Hong Kong and accommodates more than 6000 older adults in more than 70 nursing homes. In Hong Kong, nursing homes are broadly categorized into those privately owned (private homes) and those operated by charitable nonprofit making organizations (C&A nursing home). C&A nursing homes are required to follow a standard staff-to-residents ratio, with
1525-8610/$ - see front matter Published by Elsevier Inc. on behalf of the American Medical Directors Association, Inc. doi:10.1016/j.jamda.2012.05.007
T.C. Chan et al. / JAMDA 13 (2012) 630e633
comparable facility and quality of care.8 Adults aged 65 or older living in the 9 C&A nursing homes in HKWC were included for analysis. Outreach clinical services for the nursing home older adults were provided by the geriatricians of the Hong Kong West (HKW) Community Geriatric Assessment Team (CGAT). Regular health assessment was offered to the nursing home residents, which included annual blood test on renal function (ie, serum sodium, potassium, chloride, urea, and serum creatinine levels).9 Clinical data within 6 months of the study were retrieved from Hong Kong Hospital Authority Computer Management System (CMS). The subjects were categorized into 1 of the following age groups: 70 years or younger, 71 to 80, 81 to 89 and 90 years and older. The number and type of comorbidity were quantified using the Charlson Co-morbidity Index (CCI), which was validated for the use in clinical research.10e13 In our center, serum creatinine levels were measured using the modified kinetic Jaffe assay (Roche Modular DDP Analyzer, Indianapolis, IN), with a laboratory coefficient of variation less than 1%. The adult serum creatinine references reported by our laboratory were 67 to 109 mmol/L in men and 49 to 82 mmol/L in women, respectively. In this study, the GFR was estimated by the MDRD and CKD-EPI equations (listed as follows). MDRD Chinese adjusted equation4
GFR ml=min=1:73m2
¼ 175 ðPCr Þ
1:234
0:179
ðageÞ
0:79 ðif femaleÞ PCr ¼ plasma creatinine concentration in mg/dL CKD-EPI5
GFR ml=min=1:73m2
¼ 141 minðPCr Þa maxðPCr Þ1:209 0:993Age 1:018 ðif femaleÞ
PCr ¼ plasma creatinine concentration in mg/dL a ¼ e0.329 for females and e0.411 for males, min indicates minimum of PCr, and max indicates the maximum of PCr. Patients were stratified to Stage 3 (30e59 mL/min/1.73m2) or Stage 4e5 (<30 mL/min/1.73m2) CKD according to the modified version of Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. The study was approved by the institutional review boards at the University of Hong Kong and Hospital Authority. Statistical Analysis Continuous valuables were expressed as mean SD of the mean (mean SD). Chi-square test was used to compare categorical variables and the correlations were assessed by Cramer’s Phi test (4c). Spearman’s rank correlation coefficient (r) was used to assess the correlation between (1) age and creatinine, and (2) age and GFR estimated by MDRD and CKD-EPI. Kendall tau rank correlation coefficient (s) was used to assess the correlation between age group and severity of renal impairment estimated by MDRD and CKD-EPI. Statistical significance was inferred by a 2-tailed P value of .05 or less. All statistical analyses were performed by Statistical Package for Social Science (Windows version 18; SPSS Inc, Chicago, IL). Results A total of 812 older adults were included for analysis and their clinical characteristics are summarized in Table 1. The mean age was 86.0 7.6 with a mean Charlson’s score of 2.85 1.5. The mean creatinine level was 96.4 50.7 mmol/L. The mean GFR was 75.1 31.7 mL/min/1.73m2 by MDRD and 76.5 24.0 mL/min/1.73m2 by CKD-EPI. GFR estimated by MDRD or CKD-EPI equations decreased with increasing age (for MDRD: r ¼ e0.08, P < .001; for CKD-EPI:
631
Table 1 Clinical Characteristics of 812 Chinese Nursing Home Older Adults
Age, mean SD <70, n (%) 71e80, n (%) 81e90, n (%) >91, n (%) Charlson Comorbidity Index, mean SD Hypertension, n (%) Diabetes, n (%) Arrhythmia, n (%) Congestive heart failure, n (%) Peripheral vascular disease, n (%) Chronic obstructive pulmonary disease, n (%) Cerebrovascular disease, n (%) Creatinine, mmol/L, mean SD MDRD-GFR, mL/min/1.73m2, mean SD CKD-EPI-GFR, mL/min/1.73m2, mean SD
Male (n ¼ 271)
Female (n ¼ 541)
Overall (n ¼ 812)
83.8 7.6 12 (4.4) 79 (29.2) 124 (45.8) 56 (20.7) 2.83 1.54
87.1 7.4 9 (1.7) 90 (16.6) 267 (49.4) 175 (32.3) 2.87 1.49
86.0 7.6 21 (2.6) 169 (20.8) 391 (48.2) 231 (28.4) 2.85 1.5
168 84 26 37 9 37
348 139 62 95 22 43
516 223 88 132 31 80
(62) (31.0) (9.6) (13.7) (3.3) (13.7)
(64.3) (25.7) (11.5) (17.6) (4.1) (7.9)
(63.5) (27.5) (10.8) (16.3) (3.8) (9.9)
63 (23.3) 101.7 44.5 78.3 30.1
102 (18.8) 93.7 53.4 73.5 32.4
165 (20.3) 96.4 50.7 75.1 31.7
69.9 19.7
79.8 25.2
76.5 24.0
CKD-EPI-GFR, glomerular filtration rate by The Chronic Kidney Disease Epidemiology Collaboration equation; MDRD-GFR, glomerular filtration rate by Modification of Diet in Renal Disease equation.
r ¼ e0.14, P < .001) but serum creatinine level did not correlate with age (r ¼ e0.018, P ¼ .56). Using the MDRD and CKD-EPI equations, 26.4% and 21.2% of older adults had Stage 3 whereas 6.8% and 4.4% had Stage 4e5 CKD respectively (Table 2). With the MDRD equation, the prevalence of Stage 3 or Stage 4e5 CKD were 21.4% and 4.8%, 23.8% and 5.4 %, 27.3% and 7.7% as well as 29.6% and 8.5% for patients aged younger than 70, 71 to 80, 81 to 90, and 91 or older, respectively. With the CKD-EPI equation, the prevalence of Stage 3 and Stage 4e5 CKD were 14.3% and 0%, 16.6% and 3.6 %, 22.3% and 4.3%, and 23.4% and 5.6% for patients aged younger than 70, 71 to 80, 81 to 90, and 91 or older, respectively. The prevalence of Stage 3e5 CKD estimated by the MDRD or CKD-EPI equations increased with age group (For MDRD: s ¼ 0.08; P < .01; for CKD-EPI: s ¼ 0.13; P < .001) (Figure 1), whereas the prevalence of abnormal serum creatinine levels did not correlate with age group (s ¼ 0.02, P ¼ .56). Using the MDRD equation to estimate the GFR, the following factors significantly correlated with Stage 3e5 CKD (ie, GFR< 60 mL/ min/1.73m2): diabetes mellitus (DM) (4c ¼ 0.19; P < .001), hypertension (HT) (4c ¼ 0.13; P < .001), congestive heart failure (CHF) (4c ¼ 0.16; P < .001), and ischemic heart disease (IHD) (4c ¼ 0.09; P < .01). Similarly, these 4 factors significantly correlated with Stages 3 to 5 CKD in Chinese nursing home residents with calculations based on the CKD-EPI equations. When further stratified to Stage 3 (GFR 30e59 mL/min/1.73m2) or Stage 4e5 (<30 mL/min/1.73m2) CKD, DM, HT, Table 2 Prevalence of Moderate and Severe Renal Impairment in 812 Chinese Nursing Home Older Adults
MDRD-GFR 30e59c (n ¼ 214) <30 (n ¼ 55) CKD-EPI-GFR 30e59 (n ¼ 172) <30 (n ¼ 36) Serum creatinine Above laboratory reference limit (n ¼ 150)
Male (n ¼ 271), n (%)
Female (n ¼ 541), n (%)
Overall (n ¼ 812), %
65 (24.0) 10 (3.7)
149 (27.5) 45 (8.3)
26.4 6.8
68 (25.1) 12 (4.4)
104 (19.2) 24 (4.4)
21.2 4.4
44 (16.2)
106 (19.6)
18.4
Units are in mL/min/1.73m2. CKD-EPI-GFR, glomerular filtration rate by The Chronic Kidney Disease Epidemiology Collaboration equation; MDRD-GFR, glomerular filtration rate by Modification of Diet in Renal Disease equation.
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T.C. Chan et al. / JAMDA 13 (2012) 630e633
Age
Age
>59 MDRD-GFR
<70
71-80
81-90
>91
73.8
70.8
65
61.9
71-80
81-90
>91
>59
85.7
79.9
73.4
71
30-59
14.3
16.5
22.3
23.4
<30
0
3.6
4.3
5.6
de
CKD-EPI-GFR
bc 2
<70
30-59
21.4
23.8
27.3
29.6
<30
4.8
5.4
7.7
8.5
(ml/min/1.73m )
(ml/min/1.73m2)
a. Correlated by Kendall tau rank correlation coefficient ( ) b. MDRD-GFR: Glomerular filtration rate by Modification of Diet in Renal Disease equation c. Kendall tau rank correlation coefficient ( ) =0.08; p<0.01 d. CKD-EPI-GFR: Glomerular filtration rate by The Chronic Kidney Disease Epidemiology Collaboration equation e.
=0.13; 0<0.001
Fig. 1. Prevalence of moderate or severe renal impairment in different age groups.*
CHF, and IHD remained to correlate with these 2 severities of renal impairment respectively (Table 3). Discussion To our knowledge, this was the first study that examined the prevalence of renal impairment among Chinese nursing home older adults. In the present study, 33.2% and 25.6% had Stages 3 to 5 CKD estimated by the MDRD and CKD-EPI equations, respectively. In this study, the prevalence of renal impairment determined by estimated GFR using the MDRD or CKD-EPI equations was much higher than the prevalence of 18.4% by elevated serum creatinine levels. Although serum creatinine is a more convenient method to assess renal impairment, its level is affected by multiple factors, including muscle mass, dietary protein intake, and renal tubular secretion.14 With aging, the decline in muscle mass may mask the increase in serum creatinine level expected with a decline in renal function and such discrepancy is even more significant among nursing home elderly.15e17 Hence, identification of older adults with renal impairment by the MDRD or CKD-EPI equations would be more preferable to prevent inappropriate prescriptions and dosage adjustments.18 Compared with the MDRD equations, the prevalence of Stage 3 or Stage 4 and 5 CKD were both lower when estimation of GFR was done
by the CKD-EPI equation (Stage 3 CKD: MDRD 26.4% vs CKD-EPI 21.2%; Stage 4e5 CKD: MDRD 6.8% vs CKD-EPI 4.4%). This discrepancy might be accounted for by the intrinsic difference between the 2 equations; however, the MDRD equation may appear to be more reliable in this setting because this equation was validated previously in Chinese adults whereas the CKD-EPI did not have such validation. In this study, Table 3 Comorbidities That Correlate Significantly With Moderate or Severe Renal Impairment in Chinese Nursing Home Older Adults MDRD-GFR
DM HT CHF IHD
CKD-EPI-GFR
<60
30e59
<30
<60
30e59
<30
0.19z 0.13z 0.16z 0.09y
0.16z 0.13z 0.13z 0.07*
0.19z 0.07* 0.16z 0.11y
0.17z 0.09y 0.13z 0.10y
0.14z 0.10y 0.12z 0.10y
0.15z 0.04* 0.10* 0.05*
Significance was assessed by chi-square test and the correlation coefficient was assessed Cramer’s Phi test (4c). Units are in mL/min/1.73m2. CHF, congestive heart failure; CKD-EPI-GFR, glomerular filtration rate by The Chronic Kidney Disease Epidemiology Collaboration equation; DM, diabetes mellitus; HT, hypertension; IHD, ischemic heart disease; MDRD-GFR, glomerular filtration rate by Modification of Diet in Renal Disease equation. *P < .05. y P < .01. z P < .001.
T.C. Chan et al. / JAMDA 13 (2012) 630e633
we did not estimate GFR with the Cockcroft-Gault (CG) equation, although this is another commonly used and well-validated equation for estimating GFR.19 The CG equation was derived from Caucasians and had not been validated in Chinese. Therefore, the use of a Chinese-validated MDRD equation may be more appropriate than the CG equation to estimate GFR in our study. As shown in previous studies, the use of the CG equation may be associated with more underestimation of reduced GFR when compared with the MDRD and CKD-EPI equations,20,21 although a definitive conclusion cannot be drawn from our data because we had not applied the CG equation in our study. Currently, the CG equation is the standard for dose adjustment of medications in the face of renal impairment. 22 Although both the MDRD and CG equations may be misleading in the very old, one should appreciate that the package inserts of most prescription drugs use the CG equation to determine dosages, and errors may be introduced by applying the MDRD equation for dosage adjustment. In this regard, it would be desirable to also include dosage adjustment according to MDRD equation in the package inserts.23 Our data suggested that DM, HT, CHF, and IHD correlate significantly with renal impairment in Chinese nursing home older adults. Although a causal-relationship cannot be drawn from this crosssectional analysis, we believe that it is still worthwhile to regularly monitor for renal disease among nursing home older adults presented with these comorbidities. This approach might detect early kidney dysfunction and offer timely management for these patients. Furthermore, optimal management of these comorbidities and renal impairment may reduce mortality.24 Angiotensin-converting enzyme inhibitor can be used in these older adults to retard renal deterioration.25,26 Aspirin and statin should be considered to reduce the cardiovascular risk.27,28 In addition, the early identification of older adults with stage 4e5 CKD also facilitates advance care planning including preparation for dialysis or palliative renal care.29,30 There were several limitations in this study. First, we used MDRD and CKD-EPI equations, which may overestimate or underestimate GFR. The accuracy of creatinine clearance measurement can be improved with 24-hour urine collection, but such approach is costly, cumbersome, and may not be feasible in many nursing home older adults because of their functional limitation (eg, urinary incontinence). Instead, we believe that GFR estimation by MDRD or CKD-EPI provides a good alternative that is practical and feasible. Second, the CCI was quantified based on the ICD-9-CM coding in CMS but there is always undercoding in real clinical practice. Add to that, the variability in disease severity may not be adequately captured by the ICD9-CM coding. Third, this study was conducted among the C&A nursing homes in the HKWC, where the conditions might be different from private nursing homes and nursing homes in other districts. Such shortcomings might limit the generalizability of our result. However, our study has included a good number of patients from different nursing homes in the HKWC and hence we believe that our data closely resemble the realistic clinical situation among the Chinese nursing home older adults. Conclusion Stages 3 to 5 CKD are prevalent in Chinese nursing home older adults. Early identification of these patients allows timely management of their renal conditions, appropriate drug prescription, and dosage adjustment as well as optimal advance care planning. Acknowledgment The authors thank Dr Matthew C. W. Yeung, Department of Biochemistry, Queen Mary Hospital, Hong Kong, for providing method of serum creatinine level measurements in the Queen Mary Hospital.
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References 1. Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985;33:278e285. 2. National Kidney Foundation. Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:1e266. 3. Wong NA, Jones HW. An analysis of discharge drug prescribing amongst elderly patients with renal impairment. Postgrad Med J 1998;74:420e422. 4. Ma YC, Zuo L, Chen JH, et al. Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 2006;17:2937e2944. 5. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604e612. 6. Stengel B, Metzger M, Froissart M, et al. Epidemiology and prognostic significance of chronic kidney disease in the elderly: The three city prospective cohort study. Nephrol Dial Transplant 2011;26:3286e3295. 7. Garg AX, Papaioannou A, Ferko N, et al. Estimating the prevalence of renal insufficiency in seniors requiring long-term care. Kidney International 2004; 65:649e653. 8. Tang M, Woo J, Hui E, et al. Utilization of emergency room and hospitalization by Chinese nursing home residents. A cross-sectional study. J Am Med Dir Assoc 2010;11:325e332. 9. Luk JKH, Pau MML, Chan FHW, Yu C. Outreach geriatric private nursing home service in Hong Kong Central and Western cluster. JHK Geriatr Soc 2002;11: 5e10. 10. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 1987;40:373e383. 11. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative database. J Clin Epidemiol 1992;45:613e619. 12. Groot V, Beckerman H, Lankhorst GJ, et al. How to measure comorbidity: A critical review of available methods. J Clin Epidemiol 2003;56:221e229. 13. Schneeweiss S, Maclure M. Use of comorbidity scores for control of confounding in studies using administrative databases. Int J Epidemiol 2000;29: 891e898. 14. Hsu CY, Chertow GM, Curhan GC, et al. Methodological issues in studying the epidemiology of mild to moderate chronic renal insufficiency. Kidney Int 2002; 13:2812e2816. 15. Puyol DR. The aging kidney. Kidney Int 1998;54:2247e2265. 16. Epstein M. Aging and the kidney. J Am Soc Nephrol 1996;7:1106e1122. 17. Salive ME, Jones CA, Guralnik JM, et al. Serum creatinine levels in older adults: Relationship with health status and medications. Age Aging 1995;24: 142e150. 18. Corsonello A, Pedone C, Lattanzio F, et al. Association between glomerular filtration rate and adverse drug reactions in elderly hospitalized patients: The role of the estimating equation. Drugs Aging 2011;28:379e390. 19. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31e41. 20. Nicoll SR, Sainsbury R, Bailey RR, et al. Assessment of creatinine clearance in healthy subjects over 65 years of age. Nephron 1991;59:621e625. 21. Dharmarajan TS, Yoo J, Russell RO, et al. Chronic kidney disease staging in nursing home and community older adults: Does the choice of Cockcroft-Gault, Modification of Diet in Renal Disease Study, or the Chronic Kidney Disease Epidemiology Collaboration Initiative Equations matter? J Am Med Dir Assoc 2012;13:151e155. 22. Food and Drug Administration. Guidance for industry: Pharmacokinetics in patients with impaired renal function; study design, data analysis, and impact on dosing and labeling. US Department of Health and Human Services; 1998. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInfor mation/Guidances/ucm072127.pdf, accessed May 30, 2012. 23. Stevens LA, Nolin TD, Richardson MM, et al. Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations. Am J Kidney Dis 2009;54:33e42. 24. Feldman SM, Rosen R, Destasio J. Status of diabetes management in nursing home setting in 2008: A retrospective chart review and epidemiology study of diabetic nursing home residents and nursing home initiatives in diabetes management. J Am Med Dir Assoc 2009;10:354e360. 25. Ahmed A, Kiefe CL, Allman RM, et al. Survival benefits of angiotensin converting enzyme inhibitors in older heart failure patients with perceived contraindications. J Am Geriatr Soc 2002;50:1659e1666. 26. Mann JFE, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: The HOPE randomized trial. Ann Intern Med 2001;134:629e636. 27. Levy CR, Radcliff TA, Williams ET, et al. Acute myocardial infarction in nursing home residents: Adherence to treatment guidelines reduces mortality, but why is adherence so low? J Am Med Dir Assoc 2009;10:56e61. 28. Parikh S, Shrank WH, Mogun H, et al. Statin utilization in nursing home patients after cardiac hospitalization. J Gen Intern Med 2010;12:1293e1299. 29. Chu LW, Luk JK, Hui E, et al. Advance directive and end-of-life care preferences among Chinese nursing home residents in Hong Kong. J Am Med Dir Assoc 2011;12:143e152. 30. Yu AW, Chau KF, Ho YW, et al. Development of the “peritoneal dialysis first” model in Hong Kong. Perit Dial Int 2007;27:53e55.