- Email: [email protected]
Awareness of CKD in China: A National Cross-sectional Survey
Correspondence
Reference 1. Weiner DE, Tighiouart H, Ladik V, Meyer KB, Zager PG, Johnson DS. Oral intradialytic nutritional supplement use and mortality in hemodialysis patients. Am J Kidney Dis. 2014;63(2): 276-285. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2013.11.030
In Reply to ‘Etiological Versus Prognostic Models in Cohort Studies’ and ‘Nutritional Supplement Use in Hemodialysis Patients’ We thank Dr Imamovic1 and Drs Bossola and Tazza2 for their comments on our report,3 and acknowledge their stated limitations and caveats associated with cohort data.4 In our analyses using clinical data, we focused on the most reliable data—specifically, laboratory results and demographic data. We incorporated available indicators of nutrition, inflammation, and health status into models,5 including some of the most important predictors of outcomes in hemodialysis patients6; variables in the propensity match, as well as in adjusted models, included serum albumin level, white blood cell count, protein catabolic rate, serum creatinine levels, iron study results, vascular access type, and recent hospitalizations. We used multiple models, serially including possible confounders and mediators to explore whether results were robust. Additionally, we included time-dependent serum albumin values in the models, which showed only a small improvement in albumin levels for patients receiving supplements, suggesting that the survival benefit likely was not explained entirely by change in serum albumin level. A plausible alternative explanation for the benefit seen with protein intake during dialysis is a favorable change in anabolic-catabolic balance that precedes any substantial change in serum albumin levels, demonstrated elegantly over the past decade by Ikizler and colleagues.7,8 Randomized clinical trials are ideal for generating a firm evidence base for treatment decisions. Unfortunately, clinical trials are rare and suboptimal in nephrology.9,10 Therefore, observational methodology that leverages natural experiments to generate knowledge has an important role, particularly when the intervention, in this case oral nutritional supplements, is inexpensive and nontoxic and multiple studies show similar findings.11 When weighing the risk-benefit ratio, whether one waits for clinical trial results that may never come or elects to implement a treatment based on experience is dependent on the individual provider and his or her assessment of this balance.12 Daniel E. Weiner, MD, MS Hocine Tighiouart, MS Tufts Medical Center Boston, Massachusetts
Acknowledgements Financial Disclosure: Dr Weiner receives support for clinical activities from DCI. Mr Tighiouart received salary support from DCI.
References 1. Imamovic G. Etiological versus prognostic models in cohort studies. Am J Kidney Dis. 2014;63:1067. 2. Bossola M, Tazza L. Nutritional supplement use in hemodialysis patients. Am J Kidney Dis. 2014;63:1067-1068. 1068
3. Weiner DE, Tighiouart H, Ladik V, Meyer KB, Zager PG, Johnson DS. Oral intradialytic nutritional supplement use and mortality in hemodialysis patients. Am J Kidney Dis. 2014;63:276-285. 4. Brunelli SM, Rassen JA. Emerging analytical techniques for comparative effectiveness research. Am J Kidney Dis. 2013;61:13-17. 5. Rambod M, Bross R, Zitterkoph J, et al. Association of malnutrition-inflammation score with quality of life and mortality in hemodialysis patients: a 5-year prospective cohort study. Am J Kidney Dis. 2009;53:298-309. 6. Lacson E Jr, Wang W, Hakim RM, Teng M, Lazarus JM. Associates of mortality and hospitalization in hemodialysis: potentially actionable laboratory variables and vascular access. Am J Kidney Dis. 2009;53:79-90. 7. Ikizler TA, Flakoll PJ, Parker RA, Hakim RM. Amino acid and albumin losses during hemodialysis. Kidney Int. 1994;46:830-837. 8. Pupim LB, Majchrzak KM, Flakoll PJ, Ikizler TA. Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis patients with deranged nutritional status. J Am Soc Nephrol. 2006;17:3149-3157. 9. Deo A, Schmid CH, Earley A, Lau J, Uhlig K. Loss to analysis in randomized controlled trials in CKD. Am J Kidney Dis. 2011;58:349-355. 10. Palmer SC, Sciancalepore M, Strippoli GF. Trial quality in nephrology: how are we measuring up? Am J Kidney Dis. 2011;58: 335-337. 11. Lacson E Jr, Wang W, Zebrowski B, Wingard R, Hakim RM. Outcomes associated with intradialytic oral nutritional supplements in patients undergoing maintenance hemodialysis: a quality improvement report. Am J Kidney Dis. 2012;60:591-600. 12. Wright S, Weiner DE. Oral nutritional supplement use in dialysis patients: full speed ahead? Am J Kidney Dis. 2012;60:507-509. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.04.001
RESEARCH LETTERS Awareness of CKD in China: A National Cross-sectional Survey To the Editor: Chronic kidney disease (CKD) has received increased attention as a public health problem worldwide. A recent national crosssectional survey in China showed that the overall prevalence of CKD was 10.8%.1 Unfortunately, despite global efforts to heighten the public concern surrounding kidney disease, awareness of CKD remains low. In this study, we investigated the awareness of CKD in China using data from the China National Survey of CKD. We obtained a representative sample of people 18 years or older in the general population using multistage stratified sampling. Altogether, 50,550 people were invited to participate, of whom 47,204 completed the survey. Among them, 4,443 participants who met the criteria for CKD were included in the present study. CKD was defined as urinary albumin-creatinine ratio . 30 mg/g and/or estimated glomerular filtration rate , 60 mL/min/1.73 m2, consistent with NKF-KDOQI guidelines.2 CKD awareness was determined by self-reported answer to the question, “Have you ever been told by a doctor that you have kidney disease (excluding frank pain, or diagnosis of renal weakness by Chinese traditional medicine)?” Those answering affirmatively were considered to be aware of their condition. We analyzed the factors potentially associated with awareness of CKD using logistic regression models. Age- and sex-adjusted and multivariable-adjusted odds ratios with 95% confidence Am J Kidney Dis. 2014;63(6):1066-1075
Correspondence Table 1. Rate of Awareness of CKD at Different Levels of eGFR and Albuminuria Normoalbuminuria
Albuminuria
— —
eGFR $ 90 mL/min/1.73 m2 eGFR 5 60-89 mL/min/1.73 m2 eGFR 5 30-59 mL/min/1.73 m2 eGFR , 30 mL/min/1.73 m2
7.7% 9.6% 16.7% 61.8%
11.7% (95% CI, 9.5%-13.8%) 15.6% (95% CI, 5.0%-26.1%)
intervals were reported. Covariates included in the analyses were classified into 3 categories: (1) access to health care (including type of insurance, income, and having received a health examination during the previous 2 years); (2) presence of risk factors for CKD, including hypertension, diabetes, and cardiovascular disease; and (3) personal self-reported concern regarding kidney disease (defined as including “kidney disease” in the answer to the question “Please list 3 diseases that concern you most” in the questionnaire), family history of kidney disease, and education. The overall awareness rate of CKD was 10.04%. The awareness rate of CKD was higher for those in an advanced stage of CKD and those with albuminuria (Table 1). Compared with those unaware of CKD, participants who were aware of their condition were more educated and were more likely to possess free medical insurance, have received a health examination during the previous 2 years, have a family history of kidney disease, self-report concern about kidney disease, and have hypertension. Participants with CKD risk factors constituted 64.1% of patients with CKD, but of these, only 33.6% reported receiving a health examination during the previous 2 years. Routine urine tests and measurement of serum creatinine were included in only 51.3% and 28.4% of health examinations, respectively. The presence of risk factors for CKD and access to health care were not associated with awareness. After adjusting for
(95% (95% (95% (95%
CI, CI, CI, CI,
6.5%-8.9%) 8.1%-11.2%) 11.8%-21.7%) 45.4%-78.1%)
potential confounders, self-reported concern regarding kidney disease (OR, 5.09; 95% CI, 3.54-7.32), family history of kidney disease (OR, 4.81; 95% CI, 2.97-7.77), and education level of high school or more (OR, 1.69; 95% CI, 1.29-2.19) were associated with awareness of CKD (Table 2). Our nationwide survey indicates that awareness of CKD is low in China, even for patients with CKD stages 4-5. The awareness rate is not associated with access to health care or presence of risk factors for CKD, as previously presumed. Instead, personal concern regarding CKD is associated independently with awareness of CKD. Limited access to health care resources has been suggested as a major impediment to adequate care of patients with CKD.3 It is estimated that ,10% of patients with CKD stage 5 in certain developing countries receive renal replacement therapy due to high costs and lack of access.4 However, in our study, no independent association was observed between access to health care and awareness of CKD in China. Therefore, strategies other than improving health care access should be considered to improve CKD awareness. Hypertension, diabetes, and cardiovascular diseases are widely acknowledged as risk factors for CKD. In our study, although one-third of participants with these risk factors had received health examinations in the recent past, tests for indicators of kidney damage were not performed routinely during these examinations. Hence, educational campaigns prompting screening
Table 2. Characteristics of Participants and Odds of Being Aware of CKD Unaware (n 5 3,997)
Aware (n 5 446)
57.2 6 15.6b
58.5 6 15.0b
Male sex
37.7%
43.1%
Incomec Tertile 1 Tertile 2 Tertile 3
35.1% 35.8% 29.1%
37.7% 35.7% 26.7%
1.00 (reference) 0.92 (0.72-1.17) 0.87 (0.67-1.13)
1.00 (reference) 0.91 (0.70-1.17) 0.85 (0.64-1.12)
1.48 (1.19-1.84)
1.69 (1.29-2.19) 1.22 1.12 1.33 0.73 1.00
Age (y)
Age- and Sex-Adjusted OR (95% CI)
— —
Multivariable Adjusteda OR (95% CI) 1.01 (1.00-1.02) 0.87 (0.70-1.07)
Education $ high school
28.5%
36.1%d
Insurance Free medical insurance Basic medical insurance New rural cooperative medical care Other No insurance
—
—d
9.3% 29.6% 44.4% 7.2% 9.6%
11.9% 31.8% 44.4% 4.9% 7.0%
1.65 1.43 1.36 0.83 1.00
Health exam in previous 2 y
32.7%
39.9%d
1.27 (1.03-1.57)
1.26 (1.00-1.59)
Self-reported concern of kidney disease
4.4%
21.1%d
5.01 (3.51-7.14)
5.09 (3.54-7.32)
Family history of kidney disease
1.5%
7.0%d
5.34 (3.41-8.38)
4.81 (2.97-7.77)
History of CVD
5.5%
7.0%d
1.14 (0.76-1.70)
1.12 (0.74-1.70)
Hypertension
58.3%
63.5%d
0.99 (0.94-1.04)
0.98 (0.93-1.04)
Diabetes
17.0%
20.0%
1.17 (0.91-1.50)
1.14 (0.88-1.49)
Scr $ 1.5 mg/dL
4.5%
16.4%d
Proteinuria
86.9%
87.4%
(1.04-2.64) (0.95-2.15) (0.92-2.02) (0.46-1.50) (reference)
— —
(0.74-2.01) (0.73-1.72) (0.87-2.04) (0.40-1.34) (reference)
— —
Abbreviations: CI, confidence interval; CVD, cardiovascular disease; OR, odds ratio; Scr, serum creatinine. a Odds ratio was adjusted for age, sex, and all covariates listed in the table (except for Scr $ 1.5 mg/dL and proteinuria). b Mean 6 standard deviation. c In order of increasing income. d P , 0.05 versus those unaware.
Am J Kidney Dis. 2014;63(6):1066-1075
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Correspondence for CKD in high-risk populations should be strengthened in China. Because most of these patients are under the care of primary physicians or specialists other than nephrologists, it is important to include those health professionals in the campaign. Furthermore, our results indicate that personal concern regarding CKD is highly predictive of awareness, so education targeting high-risk populations also could be effective. In conclusion, CKD awareness in China is low, even in those with advanced stages of kidney disease. Besides improving access to health care, educational campaigns aiming at screening for CKD in high-risk populations could be effective to improve CKD awareness. Both health professionals and the public should be involved in such programs. Fang Wang, MD, Luxia Zhang, MD, MPH Haiyan Wang, MD, on behalf of the China National Survey of CKD Working Group Peking University First Hospital, Peking, China Corresponding author: [email protected]
Acknowledgements Members of the China National Survey of CKD Working Group include Li Wang, MD; Wenke Wang, MD; Bicheng Liu, MD; Jian Liu, MD; Menghua Chen, MD; Qiang He, MD; Yunhua Liao, MD; Xueqing Yu, MD; Nan Chen MD; Jian-e Zhang, MD; Zhao Hu, MD; Fuyou Liu, MD; Daqing Hong, MD; Lijie Ma, MD; Hong Liu, MD; Xiaoling Zhou, MD; Jianghua Chen, MD; Ling Pan, MD; Wei Chen, MD; Weiming Wang, MD; and Xiaomei Li, MD. Support: This study was supported by the National Key Technology R&D Program from the Ministry of Science and Technology (China; 2007BAI04B10); grants to Dr Luxia Zhang for the Early Detection and Prevention of Non-communicable Chronic Diseases from the International Society of Nephrology and the Fund for Early Diagnosis and Evaluation of Progression for CKD from the Beijing Municipal Science and Technology Commission (D131100004713007). Financial Disclosure: The authors declare that they have no other relevant financial interests.
unusual in ADPKD (,25% of patients have levels . 300 mg/d), but proteinuria is a risk factor for rapid cyst growth and the development of ESRD.2-4 Based on a limited number of biopsies in ADPKD patients with heavy proteinuria, the most common underlying pathologic changes are focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease.5 The traditional Chinese medicine Tripterygium wilfordii (also called thunder god vine or Lei Gong Teng) contains triptolide and has been used widely as an effective antiproteinuric. Tripterygium has an impressive antiproteinuric effect in various forms of CKD, including the pathologic lesions mentioned.6 Recently, triptolide was shown in experimental studies to inhibit cyst formation and growth.7 In this uncontrolled trial, we treated 9 proteinuric ADPKD patients with Tripterygium to test for antiproteinuric and/ or cyst-inhibitory effects. The patients had been treated with losartan, 100 mg/d (Cozaar; Merck Sharp & Dohme [Sweden] AB), for at least 6 months, but continued to have a 24-hour urine protein excretion . 1 g/d. After providing informed consent, they were treated with Tripterygium at 1 mg/kg/d (Lei Gong Teng; Shanghai Fudan Forward Pharmaceutical Co Ltd) in 3 divided doses. Serum creatinine was determined by the photometric enzymatic method, and cystatin C, by particle-enhanced turbidimetric immunoassay (Modular P800; Roche Diagnostics). eGFR was calculated by the creatinine-based CKD Epidemiology Collaboration (CKD-EPI) equation. Proteinuria was determined by the biuret method in 24-hour urine collections. Abdominal magnetic resonance scans were obtained at enrollment and 6-month follow-up visits, using a previously described protocol.8 Total kidney volume (TKV) was measured twice by 2 independent observers using the Advantage Windows Workstation (GE Medical Systems Europe). Baseline characteristics of the 9 patients are shown in Table 1. Mean urinary protein excretion was 2,645 6 1,408 (range, 1,004-5,483) mg/d. After 6 months of Tripterygium treatment,
Table 1. Demographic and Clinical Characteristics of Proteinuric ADPKD Patients at Baseline
References 1. Zhang L, Wang F, Wang L, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet. 2012;379(9818): 815-822. 2. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2)(suppl 1):S1-S266. 3. Parker TF III, Blantz R, Hostetter T, et al. The chronic kidney disease initiative. J Am Soc Nephrol. 2004;15(3): 708-716. 4. Jafar TH. The growing burden of chronic kidney disease in Pakistan. N Engl J Med. 2006;354(10):995-997. Received August 23, 2013. Accepted in revised form January 1, 2014. Originally published online February 27, 2014. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.01.012
Parameter
Value 39.2 6 12.1
Age (y) Male sex
3 (33)
Body mass index (kg/m2)
23.1 6 4.1
Mean arterial pressure (mm Hg)
104 6 10
Hypertension
8 (89)
ACEi/ARB use
9 (100)
Calcium channel blocker use
2 (29)
Polycystic liver disease
7 (78)
ADPKD family history
6 (67)
History of macrohematuria
2 (22)
Total kidney volume (cm3)
1,495 6 560 1.4 6 0.8
Creatinine (mg/dL) eGFR (mL/min/1.73 m2)
75 6 42
Cystatin C (mg/L)
1.2 6 0.5
Serum urea nitrogen (mg/dL)
20.8 6 8.7
Uric acid (mmol/L)
354 6 121
Triptolide-Containing Formulation in Patients With Autosomal Dominant Polycystic Kidney Disease and Proteinuria: An Uncontrolled Trial
Hemoglobin (g/dL)
13.3 6 2.0
Albumin (g/dL)
4.2 6 0.9
To the Editor: Autosomal dominant polycystic kidney disease (ADPKD) accounts for 5%-10% of patients with ESRD, making it the most common inherited cystic renal disease.1 Overt proteinuria is
Note: Values are shown as mean 6 1 standard deviation or number (percentage). Abbreviations: ACEi/ARB, angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker; eGFR, estimated glomerular filtration rate.
1070
Cholesterol (mg/dL)
184 6 83
Triglycerides (mg/dL)
170 6 135
Am J Kidney Dis. 2014;63(6):1066-1075
Reference 1. Weiner DE, Tighiouart H, Ladik V, Meyer KB, Zager PG, Johnson DS. Oral intradialytic nutritional supplement use and mortality in hemodialysis patients. Am J Kidney Dis. 2014;63(2): 276-285. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2013.11.030
In Reply to ‘Etiological Versus Prognostic Models in Cohort Studies’ and ‘Nutritional Supplement Use in Hemodialysis Patients’ We thank Dr Imamovic1 and Drs Bossola and Tazza2 for their comments on our report,3 and acknowledge their stated limitations and caveats associated with cohort data.4 In our analyses using clinical data, we focused on the most reliable data—specifically, laboratory results and demographic data. We incorporated available indicators of nutrition, inflammation, and health status into models,5 including some of the most important predictors of outcomes in hemodialysis patients6; variables in the propensity match, as well as in adjusted models, included serum albumin level, white blood cell count, protein catabolic rate, serum creatinine levels, iron study results, vascular access type, and recent hospitalizations. We used multiple models, serially including possible confounders and mediators to explore whether results were robust. Additionally, we included time-dependent serum albumin values in the models, which showed only a small improvement in albumin levels for patients receiving supplements, suggesting that the survival benefit likely was not explained entirely by change in serum albumin level. A plausible alternative explanation for the benefit seen with protein intake during dialysis is a favorable change in anabolic-catabolic balance that precedes any substantial change in serum albumin levels, demonstrated elegantly over the past decade by Ikizler and colleagues.7,8 Randomized clinical trials are ideal for generating a firm evidence base for treatment decisions. Unfortunately, clinical trials are rare and suboptimal in nephrology.9,10 Therefore, observational methodology that leverages natural experiments to generate knowledge has an important role, particularly when the intervention, in this case oral nutritional supplements, is inexpensive and nontoxic and multiple studies show similar findings.11 When weighing the risk-benefit ratio, whether one waits for clinical trial results that may never come or elects to implement a treatment based on experience is dependent on the individual provider and his or her assessment of this balance.12 Daniel E. Weiner, MD, MS Hocine Tighiouart, MS Tufts Medical Center Boston, Massachusetts
Acknowledgements Financial Disclosure: Dr Weiner receives support for clinical activities from DCI. Mr Tighiouart received salary support from DCI.
References 1. Imamovic G. Etiological versus prognostic models in cohort studies. Am J Kidney Dis. 2014;63:1067. 2. Bossola M, Tazza L. Nutritional supplement use in hemodialysis patients. Am J Kidney Dis. 2014;63:1067-1068. 1068
3. Weiner DE, Tighiouart H, Ladik V, Meyer KB, Zager PG, Johnson DS. Oral intradialytic nutritional supplement use and mortality in hemodialysis patients. Am J Kidney Dis. 2014;63:276-285. 4. Brunelli SM, Rassen JA. Emerging analytical techniques for comparative effectiveness research. Am J Kidney Dis. 2013;61:13-17. 5. Rambod M, Bross R, Zitterkoph J, et al. Association of malnutrition-inflammation score with quality of life and mortality in hemodialysis patients: a 5-year prospective cohort study. Am J Kidney Dis. 2009;53:298-309. 6. Lacson E Jr, Wang W, Hakim RM, Teng M, Lazarus JM. Associates of mortality and hospitalization in hemodialysis: potentially actionable laboratory variables and vascular access. Am J Kidney Dis. 2009;53:79-90. 7. Ikizler TA, Flakoll PJ, Parker RA, Hakim RM. Amino acid and albumin losses during hemodialysis. Kidney Int. 1994;46:830-837. 8. Pupim LB, Majchrzak KM, Flakoll PJ, Ikizler TA. Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis patients with deranged nutritional status. J Am Soc Nephrol. 2006;17:3149-3157. 9. Deo A, Schmid CH, Earley A, Lau J, Uhlig K. Loss to analysis in randomized controlled trials in CKD. Am J Kidney Dis. 2011;58:349-355. 10. Palmer SC, Sciancalepore M, Strippoli GF. Trial quality in nephrology: how are we measuring up? Am J Kidney Dis. 2011;58: 335-337. 11. Lacson E Jr, Wang W, Zebrowski B, Wingard R, Hakim RM. Outcomes associated with intradialytic oral nutritional supplements in patients undergoing maintenance hemodialysis: a quality improvement report. Am J Kidney Dis. 2012;60:591-600. 12. Wright S, Weiner DE. Oral nutritional supplement use in dialysis patients: full speed ahead? Am J Kidney Dis. 2012;60:507-509. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.04.001
RESEARCH LETTERS Awareness of CKD in China: A National Cross-sectional Survey To the Editor: Chronic kidney disease (CKD) has received increased attention as a public health problem worldwide. A recent national crosssectional survey in China showed that the overall prevalence of CKD was 10.8%.1 Unfortunately, despite global efforts to heighten the public concern surrounding kidney disease, awareness of CKD remains low. In this study, we investigated the awareness of CKD in China using data from the China National Survey of CKD. We obtained a representative sample of people 18 years or older in the general population using multistage stratified sampling. Altogether, 50,550 people were invited to participate, of whom 47,204 completed the survey. Among them, 4,443 participants who met the criteria for CKD were included in the present study. CKD was defined as urinary albumin-creatinine ratio . 30 mg/g and/or estimated glomerular filtration rate , 60 mL/min/1.73 m2, consistent with NKF-KDOQI guidelines.2 CKD awareness was determined by self-reported answer to the question, “Have you ever been told by a doctor that you have kidney disease (excluding frank pain, or diagnosis of renal weakness by Chinese traditional medicine)?” Those answering affirmatively were considered to be aware of their condition. We analyzed the factors potentially associated with awareness of CKD using logistic regression models. Age- and sex-adjusted and multivariable-adjusted odds ratios with 95% confidence Am J Kidney Dis. 2014;63(6):1066-1075
Correspondence Table 1. Rate of Awareness of CKD at Different Levels of eGFR and Albuminuria Normoalbuminuria
Albuminuria
— —
eGFR $ 90 mL/min/1.73 m2 eGFR 5 60-89 mL/min/1.73 m2 eGFR 5 30-59 mL/min/1.73 m2 eGFR , 30 mL/min/1.73 m2
7.7% 9.6% 16.7% 61.8%
11.7% (95% CI, 9.5%-13.8%) 15.6% (95% CI, 5.0%-26.1%)
intervals were reported. Covariates included in the analyses were classified into 3 categories: (1) access to health care (including type of insurance, income, and having received a health examination during the previous 2 years); (2) presence of risk factors for CKD, including hypertension, diabetes, and cardiovascular disease; and (3) personal self-reported concern regarding kidney disease (defined as including “kidney disease” in the answer to the question “Please list 3 diseases that concern you most” in the questionnaire), family history of kidney disease, and education. The overall awareness rate of CKD was 10.04%. The awareness rate of CKD was higher for those in an advanced stage of CKD and those with albuminuria (Table 1). Compared with those unaware of CKD, participants who were aware of their condition were more educated and were more likely to possess free medical insurance, have received a health examination during the previous 2 years, have a family history of kidney disease, self-report concern about kidney disease, and have hypertension. Participants with CKD risk factors constituted 64.1% of patients with CKD, but of these, only 33.6% reported receiving a health examination during the previous 2 years. Routine urine tests and measurement of serum creatinine were included in only 51.3% and 28.4% of health examinations, respectively. The presence of risk factors for CKD and access to health care were not associated with awareness. After adjusting for
(95% (95% (95% (95%
CI, CI, CI, CI,
6.5%-8.9%) 8.1%-11.2%) 11.8%-21.7%) 45.4%-78.1%)
potential confounders, self-reported concern regarding kidney disease (OR, 5.09; 95% CI, 3.54-7.32), family history of kidney disease (OR, 4.81; 95% CI, 2.97-7.77), and education level of high school or more (OR, 1.69; 95% CI, 1.29-2.19) were associated with awareness of CKD (Table 2). Our nationwide survey indicates that awareness of CKD is low in China, even for patients with CKD stages 4-5. The awareness rate is not associated with access to health care or presence of risk factors for CKD, as previously presumed. Instead, personal concern regarding CKD is associated independently with awareness of CKD. Limited access to health care resources has been suggested as a major impediment to adequate care of patients with CKD.3 It is estimated that ,10% of patients with CKD stage 5 in certain developing countries receive renal replacement therapy due to high costs and lack of access.4 However, in our study, no independent association was observed between access to health care and awareness of CKD in China. Therefore, strategies other than improving health care access should be considered to improve CKD awareness. Hypertension, diabetes, and cardiovascular diseases are widely acknowledged as risk factors for CKD. In our study, although one-third of participants with these risk factors had received health examinations in the recent past, tests for indicators of kidney damage were not performed routinely during these examinations. Hence, educational campaigns prompting screening
Table 2. Characteristics of Participants and Odds of Being Aware of CKD Unaware (n 5 3,997)
Aware (n 5 446)
57.2 6 15.6b
58.5 6 15.0b
Male sex
37.7%
43.1%
Incomec Tertile 1 Tertile 2 Tertile 3
35.1% 35.8% 29.1%
37.7% 35.7% 26.7%
1.00 (reference) 0.92 (0.72-1.17) 0.87 (0.67-1.13)
1.00 (reference) 0.91 (0.70-1.17) 0.85 (0.64-1.12)
1.48 (1.19-1.84)
1.69 (1.29-2.19) 1.22 1.12 1.33 0.73 1.00
Age (y)
Age- and Sex-Adjusted OR (95% CI)
— —
Multivariable Adjusteda OR (95% CI) 1.01 (1.00-1.02) 0.87 (0.70-1.07)
Education $ high school
28.5%
36.1%d
Insurance Free medical insurance Basic medical insurance New rural cooperative medical care Other No insurance
—
—d
9.3% 29.6% 44.4% 7.2% 9.6%
11.9% 31.8% 44.4% 4.9% 7.0%
1.65 1.43 1.36 0.83 1.00
Health exam in previous 2 y
32.7%
39.9%d
1.27 (1.03-1.57)
1.26 (1.00-1.59)
Self-reported concern of kidney disease
4.4%
21.1%d
5.01 (3.51-7.14)
5.09 (3.54-7.32)
Family history of kidney disease
1.5%
7.0%d
5.34 (3.41-8.38)
4.81 (2.97-7.77)
History of CVD
5.5%
7.0%d
1.14 (0.76-1.70)
1.12 (0.74-1.70)
Hypertension
58.3%
63.5%d
0.99 (0.94-1.04)
0.98 (0.93-1.04)
Diabetes
17.0%
20.0%
1.17 (0.91-1.50)
1.14 (0.88-1.49)
Scr $ 1.5 mg/dL
4.5%
16.4%d
Proteinuria
86.9%
87.4%
(1.04-2.64) (0.95-2.15) (0.92-2.02) (0.46-1.50) (reference)
— —
(0.74-2.01) (0.73-1.72) (0.87-2.04) (0.40-1.34) (reference)
— —
Abbreviations: CI, confidence interval; CVD, cardiovascular disease; OR, odds ratio; Scr, serum creatinine. a Odds ratio was adjusted for age, sex, and all covariates listed in the table (except for Scr $ 1.5 mg/dL and proteinuria). b Mean 6 standard deviation. c In order of increasing income. d P , 0.05 versus those unaware.
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Correspondence for CKD in high-risk populations should be strengthened in China. Because most of these patients are under the care of primary physicians or specialists other than nephrologists, it is important to include those health professionals in the campaign. Furthermore, our results indicate that personal concern regarding CKD is highly predictive of awareness, so education targeting high-risk populations also could be effective. In conclusion, CKD awareness in China is low, even in those with advanced stages of kidney disease. Besides improving access to health care, educational campaigns aiming at screening for CKD in high-risk populations could be effective to improve CKD awareness. Both health professionals and the public should be involved in such programs. Fang Wang, MD, Luxia Zhang, MD, MPH Haiyan Wang, MD, on behalf of the China National Survey of CKD Working Group Peking University First Hospital, Peking, China Corresponding author: [email protected]
Acknowledgements Members of the China National Survey of CKD Working Group include Li Wang, MD; Wenke Wang, MD; Bicheng Liu, MD; Jian Liu, MD; Menghua Chen, MD; Qiang He, MD; Yunhua Liao, MD; Xueqing Yu, MD; Nan Chen MD; Jian-e Zhang, MD; Zhao Hu, MD; Fuyou Liu, MD; Daqing Hong, MD; Lijie Ma, MD; Hong Liu, MD; Xiaoling Zhou, MD; Jianghua Chen, MD; Ling Pan, MD; Wei Chen, MD; Weiming Wang, MD; and Xiaomei Li, MD. Support: This study was supported by the National Key Technology R&D Program from the Ministry of Science and Technology (China; 2007BAI04B10); grants to Dr Luxia Zhang for the Early Detection and Prevention of Non-communicable Chronic Diseases from the International Society of Nephrology and the Fund for Early Diagnosis and Evaluation of Progression for CKD from the Beijing Municipal Science and Technology Commission (D131100004713007). Financial Disclosure: The authors declare that they have no other relevant financial interests.
unusual in ADPKD (,25% of patients have levels . 300 mg/d), but proteinuria is a risk factor for rapid cyst growth and the development of ESRD.2-4 Based on a limited number of biopsies in ADPKD patients with heavy proteinuria, the most common underlying pathologic changes are focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease.5 The traditional Chinese medicine Tripterygium wilfordii (also called thunder god vine or Lei Gong Teng) contains triptolide and has been used widely as an effective antiproteinuric. Tripterygium has an impressive antiproteinuric effect in various forms of CKD, including the pathologic lesions mentioned.6 Recently, triptolide was shown in experimental studies to inhibit cyst formation and growth.7 In this uncontrolled trial, we treated 9 proteinuric ADPKD patients with Tripterygium to test for antiproteinuric and/ or cyst-inhibitory effects. The patients had been treated with losartan, 100 mg/d (Cozaar; Merck Sharp & Dohme [Sweden] AB), for at least 6 months, but continued to have a 24-hour urine protein excretion . 1 g/d. After providing informed consent, they were treated with Tripterygium at 1 mg/kg/d (Lei Gong Teng; Shanghai Fudan Forward Pharmaceutical Co Ltd) in 3 divided doses. Serum creatinine was determined by the photometric enzymatic method, and cystatin C, by particle-enhanced turbidimetric immunoassay (Modular P800; Roche Diagnostics). eGFR was calculated by the creatinine-based CKD Epidemiology Collaboration (CKD-EPI) equation. Proteinuria was determined by the biuret method in 24-hour urine collections. Abdominal magnetic resonance scans were obtained at enrollment and 6-month follow-up visits, using a previously described protocol.8 Total kidney volume (TKV) was measured twice by 2 independent observers using the Advantage Windows Workstation (GE Medical Systems Europe). Baseline characteristics of the 9 patients are shown in Table 1. Mean urinary protein excretion was 2,645 6 1,408 (range, 1,004-5,483) mg/d. After 6 months of Tripterygium treatment,
Table 1. Demographic and Clinical Characteristics of Proteinuric ADPKD Patients at Baseline
References 1. Zhang L, Wang F, Wang L, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet. 2012;379(9818): 815-822. 2. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2)(suppl 1):S1-S266. 3. Parker TF III, Blantz R, Hostetter T, et al. The chronic kidney disease initiative. J Am Soc Nephrol. 2004;15(3): 708-716. 4. Jafar TH. The growing burden of chronic kidney disease in Pakistan. N Engl J Med. 2006;354(10):995-997. Received August 23, 2013. Accepted in revised form January 1, 2014. Originally published online February 27, 2014. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.01.012
Parameter
Value 39.2 6 12.1
Age (y) Male sex
3 (33)
Body mass index (kg/m2)
23.1 6 4.1
Mean arterial pressure (mm Hg)
104 6 10
Hypertension
8 (89)
ACEi/ARB use
9 (100)
Calcium channel blocker use
2 (29)
Polycystic liver disease
7 (78)
ADPKD family history
6 (67)
History of macrohematuria
2 (22)
Total kidney volume (cm3)
1,495 6 560 1.4 6 0.8
Creatinine (mg/dL) eGFR (mL/min/1.73 m2)
75 6 42
Cystatin C (mg/L)
1.2 6 0.5
Serum urea nitrogen (mg/dL)
20.8 6 8.7
Uric acid (mmol/L)
354 6 121
Triptolide-Containing Formulation in Patients With Autosomal Dominant Polycystic Kidney Disease and Proteinuria: An Uncontrolled Trial
Hemoglobin (g/dL)
13.3 6 2.0
Albumin (g/dL)
4.2 6 0.9
To the Editor: Autosomal dominant polycystic kidney disease (ADPKD) accounts for 5%-10% of patients with ESRD, making it the most common inherited cystic renal disease.1 Overt proteinuria is
Note: Values are shown as mean 6 1 standard deviation or number (percentage). Abbreviations: ACEi/ARB, angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker; eGFR, estimated glomerular filtration rate.
1070
Cholesterol (mg/dL)
184 6 83
Triglycerides (mg/dL)
170 6 135
Am J Kidney Dis. 2014;63(6):1066-1075