- Email: [email protected]
Prevalence of albuminuria in Australia: The AusDiab Kidney Study
Kidney International, Vol. 66, Supplement 92 (2004), pp. S22–S24
Prevalence of albuminuria in Australia: The AusDiab Kidney Study ROBERT C. ATKINS, KEVAN R. POLKINGHORNE, ESTHER M. BRIGANTI, JONATHAN E. SHAW, PAUL Z. ZIMMET, and STEVEN J. CHADBAN Department of Nephrology, Monash Medical Centre, Victoria, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Victoria, Australia; and International Diabetes Institute, Victoria, Australia
ity [3–5]. The prevalence of albuminuria may, therefore, have major implications for potential screening and intervention programs, as well as health outcomes. We therefore sought to determine the population prevalence of microalbuminuria and macroalbuminuria and to examine the effects of age, sex, glucose metabolism status determined by fasting blood glucose and oral glucose tolerance test, blood pressure, and glomerular filtration rate on prevalence.
Prevalence of albuminuria in Australia: The AusDiab Kidney Study. Background. Albuminuria is an important predictor of risk of progressive renal disease, cardiovascular disease, and mortality; however, the prevalence in the general population is not well defined. We determined estimates of the population prevalence and associations of microalbuminuria and macroalbuminuria in Australian adults; 11,247 Australians aged ≥25 years living in 42 randomly selected population clusters were tested for albuminuria (spot urine albumin:creatinine (mg/mmol): normal <3.4, microalbuminuria 3.4 to 34, macroalbuminuria >34). Methods. Prevalence of micro- and macroalbuminuria were assessed with age, sex, obesity, smoking, hypertension (≥140/90 mm Hg or known diagnosis on treatment), glucose metabolism status (WHO criteria according to fasting glucose and oral glucose tolerance test), ischemic heart and cerebrovascular disease, and low glomerular filtration rate (calculated glomerular filtration rate <60 mL/min/1.73m2 ). Results. Microalbuminuria and macroalbuminuria proteinuria were present in 6.0% and 0.6% of the population, respectively. The majority of subjects with microalbuminuria (64%) and macroalbuminuria (76%) had hypertension, and approximately half of those with albuminuria had abnormal glucose metabolism. Of all participants with microalbuminuria, 25.9% had normal blood pressure and glucose metabolism, and in this group, alternative associations of microalbuminuria included obesity (13.5%), smoking (20.7%), and low glomerular filtration rate (12.3%). Conclusion. Albuminuria is present in a small percentage of the general adult population, but is highly prevalent in subjects with hypertension and/or abnormal glucose metabolism. The majority of cases of microalbuminuria and macroalbuminuria in the general population are among those with hypertension.
METHODS The Australian Diabetes, Obesity and Lifestyle Study was a nation-wide, population-based survey, undertaken between May 1999 and December 2000, to determine the prevalence of diabetes mellitus, obesity, and cardiovascular disease risk factors. Indicators of kidney disease and assessment of kidney function was also assessed. The details of the survey have been published elsewhere [6]. Written informed consent was obtained from all individuals. Of the 11,247 subjects who completed the survey, data were available for urine albumin to creatinine ratio in 10,606 (94.3%). Information on variables used in this analysis was collected during the initial household interview. This was followed by a physical examination that included anthropometry, blood pressure measurements, collection of a fasting blood specimen and a spot morning urine specimen, and a standard 75 g oral glucose tolerance test. Albuminuria was defined in terms of urine albumin to creatinine ratio. Microalbuminuria was defined as a urine albumin to creatinine ratio 3.4 to 34 mg/mmol, and macroalbuminuria as a ratio of 34 mg/mmol or greater [7]. Glomerular filtration rate was calculated using the Cockcroft-Gault formula and adjustment for body surface area. All analyses were conducted using Stata version 8.2 (Stata Corporation, College Station, TX, USA) survey commands for analyzing complex survey data. The distribution of microalbuminuria and macroalbuminuria and identification of subgroups with
In the general population, microalbuminuria has been associated with increased risk of cardiovascular disease and premature death [1–2]. For patients with renal disease or diabetes mellitus, the presence of albuminuria is associated with an increased risk of progressive renal impairment, cardiovascular disease, and overall mortal-
Key words: albuminuria, epidemiology. C
2004 by the International Society of Nephrology S-22
Atkins et al: Prevalence of albuminuria
Table 1. Clinical characteristics of individuals with or without albuminuria No MicroMacroalbuminuria albuminuria albuminuria Totala % Male sex% Agea years Obesitya % Current smokinga % Hypertensiona % Normal blood pressure Untreated Treated Glucose metabolisma % Normal Impaired fasting glucose Impaired glucose tolerance Diabetes mellitus Hypercholesterolemiaa Ischemic heart diseasea Cerebrovascular diseasea GFR <60 mL/min/1.73m2a %
93.4 (0.6) 50.2 (0.6) 47.4 (0.7) 20.4 (1.1) 16.2 (1.8)
6.0 (0.6) 42.7 (2.1) 60.8 (1.7) 28.1 (2.9) 14.8 (1.5)
0.7 (0.1) 52.4 (14.3) 61.0 (2.6) 44.2 (11.0) 26.0 (14.4)
73.2 (1.6) 15.0 (0.9) 11.7 (0.9)
36.5 (3.8) 24.4 (1.9) 39.1(3.7)
21.5 (8.6) 34.5 (13.3) 44.0 (10.5)
78.0 (1.1) 5.7 (0.4) 10.1 (0.5) 6.2 (0.6) 65.7 (1.4) 5.3 (0.4) 2.0 (0.3) 9.5 (1.0)
47.4 (3.3) 7.3 (2.4) 20.0 (2.6) 25.5 (3.0) 75.6 (1.8) 19.2 (3.1) 5.6 (1.0) 37.8 (4.5)
57.4 (11.4) 3.6 (3.4) 7.7 (5.5) 31.3 (9.2) 82.3 (6.7) 15.9 (3.9) 11.6 (4.4) 36.3 (7.9)
GFR, glomerular filtration rate. Data are mean or percent prevalence (standard error). a < P 0.001 for a difference between the three groups. Obesity defined as body mass index ≥30 kg/m2 .
high prevalence of these urinary abnormalities was determined by cross-tabulation covariates with microalbuminuria and macroalbuminuria. RESULTS Table 1 outlines the clinical characteristics of individuals with or without albuminuria. Overall, 6.0% of subjects had microalbuminuria, and 0.7% had macroalbuminuria. Significant differences in the prevalence of albuminuria were present according to obesity, hypertension (treated and untreated), glucose metabolism, hypercholesterolemia, ischemic heart disease, cerebrovascular disease, and impaired glomerular filtration rate. Of the 6.0% of the population with microalbuminuria, the majority had hypertension, abnormal glucose metabolism, or both. Sixty-three percent of microalbuminuria was found in subjects with hypertension: 21.6% in those with hypertension alone, and 41.4% in those with hypertension and abnormal glucose metabolism; 52.5% of microalbuminuria was found in those with abnormal glucose metabolism: 26.1% in those with diabetes mellitus, 19.6% in those with impaired glucose tolerance, and 6.8% in those with impaired fasting glucose. In the participants with known diabetes mellitus, micro- and macroalbuminuria was present in 24.9% and 4.6%, respectively, whereas in those in whom diabetes mellitus was newly diagnosed as a result of the survey, 15.9% and 1.3% had micro- and macroalbuminuria, respectively. Of all participants with microalbuminuria, 25.9% had normal blood pressure and glucose metabolism, and in this group, alternative associations of microalbuminuria included obesity
S-23
in 13.5%, current smoking in 20.7%, and low glomerular filtration rate in 12.3%. Of those with macroalbuminuria, 78% were hypertensive, and 43% had abnormal glucose metabolism.
DISCUSSION This study confirms and extends previous findings documenting the prevalence of albuminuria in a large population-based cohort. The majority of cases of albuminuria were found within identifiable subgroups of the cohort. Two thirds of microalbuminuria was found in association with hypertension. Half of all cases of microalbuminuria were seen in subjects with abnormal glucose metabolism, and a similar percentage of all cases were found in subjects over 65 years of age. This information has implications at several levels of health care. From the general practitioner’s perspective, the patients found to have albuminuria at an annual check-up have a 60% probability of having hypertension. In addition, the patient has a 50% probability of having abnormal glucose metabolism, and testing for this should be considered. From a therapeutic perspective, drugs that target the renin-angiotensin pathway are known to be effective in improving renal and cardiovascular outcomes for patients with albuminuria in the setting of hypertension or abnormal glucose metabolism [8–12]—the subgroups of the population in which over 75% of cases of albuminuria reside. At a population level, screening all hypertensive individuals in the general population would identify 63.7% of cases of microalbuminuria. The AusDiab data carry significant messages about disease awareness and therapy in the community. For every subject known to have diabetes mellitus, another with previously undiagnosed diabetes mellitus was detected by fasting plasma glucose or oral glucose tolerance testing [13]. For every subject on treatment for hypertension, another was found with either undiagnosed or untreated hypertension. Thus, in the Australian community, at least, significant underdetection and consequent undertreatment of diabetes mellitus, hypertension, and proteinuria are prevalent. This situation is unlikely to be different in other communities. Appropriate identification and treatment of such individuals may have a dramatic impact on population trends in the burden of renal and cardiovascular disease.
CONCLUSION Microalbuminuria is present in a small percentage of the general population, but is highly prevalent among those with hypertension and abnormal glucose metabolism.
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Atkins et al: Prevalence of albuminuria
ACKNOWLEDGMENTS We wish to thank the participants and the AusDiab Survey Team and Steering Committee. The AusDiab Study was supported by the Commonwealth Department of Health and Aged Care, State Governments of Queensland, South Australia, Tasmania, Western Australia, and Victoria and Territory Health Services, the Australian Kidney Foundation, Diabetes Australia (Northern Territory), the International Diabetes Institute, Eli Lilly (Australia), Janssen-Cilag (Australia), Knoll Australia, Merck Lipha s.a. Alphapharm, Merck Sharp & Dohme (Australia), Pharmacia and Upjohn, Roche Diagnostics, Servier Laboratories (Australia), SmithKline Beecham International, BioRad Laboratories, HITECH Pathology, and Qantas Airways. Reprint requests to Professor Robert Atkins, Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, 168, Australia. E-mail: [email protected]
REFERENCES 1. DAMSGAARD EM, FROLAND A, JORGENSEN OD, MORGENSEN CE: Microalbuminuria as a predictor of increased mortality in elderly people. BMJ 300:297–300, 1990 2. YUDKIN JS, FORREST RD, JACKSON CA: Microalbuminuria as a predictor of vascular disease in non-diabetic subjects. Lancet 2:530–533, 1988 3. MOGENSEN CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310:356– 360, 1984
4. MOGENSEN CE: Microalbuminuria as a predictor of clinical diabetic nephropathy. Kidney Int 31:673–689, 1987 5. DAMSGAARD EM, FROLAND A, JORGENSEN OD, MORGENSEN CE: Eight to nine year mortality in known non-insulin dependent diabetics and controls. Kidney Int 41:731–735, 1992 6. DUNSTAN DW, ZIMMET PZ, WELLBORN TA, et al: The Australian Diabetes, Obesity and Lifestyle Study (AusDiab)—Methods and response rates. Diab Res Clin Prac 57:119–129, 2002 7. AMERICAN DIABETES ASSOCIATION: Standards of medical care for patients with diabetes mellitus. Diabetes Care 23(Suppl 1):S32–42, 2000 8. PARVING HH, LEHNERT H, BROCHNER-MORTENSEN J, et al: The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345:870–878, 2001 9. LEWIS EJ, HUNSICKER LG, BAIN RP, ROHDE RD: The effect of angiotensin converting enzyme inhibition on diabetic nephropathy. N Engl J Med 329:1456–1462, 1993 10. JAFAR TH, SCHMID CH, LANDA M, et al: Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med 135:73–87, 2001 11. LEWIS EJ, HUNSICKER LG, CLARKE WR, et al: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860, 2001 12. BRENNER BM, COOPER ME, DE ZEEUW D, et al: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869, 2001 13. DUNSTAN DW, ZIMMET PZ, WELLBORN TA, et al: The rising prevalence of diabetes and impaired glucose tolerance—The Australian Diabetes, Obestity and Lifestyle Study. Diabetes Care 25:829–834, 2002
Prevalence of albuminuria in Australia: The AusDiab Kidney Study ROBERT C. ATKINS, KEVAN R. POLKINGHORNE, ESTHER M. BRIGANTI, JONATHAN E. SHAW, PAUL Z. ZIMMET, and STEVEN J. CHADBAN Department of Nephrology, Monash Medical Centre, Victoria, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Victoria, Australia; and International Diabetes Institute, Victoria, Australia
ity [3–5]. The prevalence of albuminuria may, therefore, have major implications for potential screening and intervention programs, as well as health outcomes. We therefore sought to determine the population prevalence of microalbuminuria and macroalbuminuria and to examine the effects of age, sex, glucose metabolism status determined by fasting blood glucose and oral glucose tolerance test, blood pressure, and glomerular filtration rate on prevalence.
Prevalence of albuminuria in Australia: The AusDiab Kidney Study. Background. Albuminuria is an important predictor of risk of progressive renal disease, cardiovascular disease, and mortality; however, the prevalence in the general population is not well defined. We determined estimates of the population prevalence and associations of microalbuminuria and macroalbuminuria in Australian adults; 11,247 Australians aged ≥25 years living in 42 randomly selected population clusters were tested for albuminuria (spot urine albumin:creatinine (mg/mmol): normal <3.4, microalbuminuria 3.4 to 34, macroalbuminuria >34). Methods. Prevalence of micro- and macroalbuminuria were assessed with age, sex, obesity, smoking, hypertension (≥140/90 mm Hg or known diagnosis on treatment), glucose metabolism status (WHO criteria according to fasting glucose and oral glucose tolerance test), ischemic heart and cerebrovascular disease, and low glomerular filtration rate (calculated glomerular filtration rate <60 mL/min/1.73m2 ). Results. Microalbuminuria and macroalbuminuria proteinuria were present in 6.0% and 0.6% of the population, respectively. The majority of subjects with microalbuminuria (64%) and macroalbuminuria (76%) had hypertension, and approximately half of those with albuminuria had abnormal glucose metabolism. Of all participants with microalbuminuria, 25.9% had normal blood pressure and glucose metabolism, and in this group, alternative associations of microalbuminuria included obesity (13.5%), smoking (20.7%), and low glomerular filtration rate (12.3%). Conclusion. Albuminuria is present in a small percentage of the general adult population, but is highly prevalent in subjects with hypertension and/or abnormal glucose metabolism. The majority of cases of microalbuminuria and macroalbuminuria in the general population are among those with hypertension.
METHODS The Australian Diabetes, Obesity and Lifestyle Study was a nation-wide, population-based survey, undertaken between May 1999 and December 2000, to determine the prevalence of diabetes mellitus, obesity, and cardiovascular disease risk factors. Indicators of kidney disease and assessment of kidney function was also assessed. The details of the survey have been published elsewhere [6]. Written informed consent was obtained from all individuals. Of the 11,247 subjects who completed the survey, data were available for urine albumin to creatinine ratio in 10,606 (94.3%). Information on variables used in this analysis was collected during the initial household interview. This was followed by a physical examination that included anthropometry, blood pressure measurements, collection of a fasting blood specimen and a spot morning urine specimen, and a standard 75 g oral glucose tolerance test. Albuminuria was defined in terms of urine albumin to creatinine ratio. Microalbuminuria was defined as a urine albumin to creatinine ratio 3.4 to 34 mg/mmol, and macroalbuminuria as a ratio of 34 mg/mmol or greater [7]. Glomerular filtration rate was calculated using the Cockcroft-Gault formula and adjustment for body surface area. All analyses were conducted using Stata version 8.2 (Stata Corporation, College Station, TX, USA) survey commands for analyzing complex survey data. The distribution of microalbuminuria and macroalbuminuria and identification of subgroups with
In the general population, microalbuminuria has been associated with increased risk of cardiovascular disease and premature death [1–2]. For patients with renal disease or diabetes mellitus, the presence of albuminuria is associated with an increased risk of progressive renal impairment, cardiovascular disease, and overall mortal-
Key words: albuminuria, epidemiology. C
2004 by the International Society of Nephrology S-22
Atkins et al: Prevalence of albuminuria
Table 1. Clinical characteristics of individuals with or without albuminuria No MicroMacroalbuminuria albuminuria albuminuria Totala % Male sex% Agea years Obesitya % Current smokinga % Hypertensiona % Normal blood pressure Untreated Treated Glucose metabolisma % Normal Impaired fasting glucose Impaired glucose tolerance Diabetes mellitus Hypercholesterolemiaa Ischemic heart diseasea Cerebrovascular diseasea GFR <60 mL/min/1.73m2a %
93.4 (0.6) 50.2 (0.6) 47.4 (0.7) 20.4 (1.1) 16.2 (1.8)
6.0 (0.6) 42.7 (2.1) 60.8 (1.7) 28.1 (2.9) 14.8 (1.5)
0.7 (0.1) 52.4 (14.3) 61.0 (2.6) 44.2 (11.0) 26.0 (14.4)
73.2 (1.6) 15.0 (0.9) 11.7 (0.9)
36.5 (3.8) 24.4 (1.9) 39.1(3.7)
21.5 (8.6) 34.5 (13.3) 44.0 (10.5)
78.0 (1.1) 5.7 (0.4) 10.1 (0.5) 6.2 (0.6) 65.7 (1.4) 5.3 (0.4) 2.0 (0.3) 9.5 (1.0)
47.4 (3.3) 7.3 (2.4) 20.0 (2.6) 25.5 (3.0) 75.6 (1.8) 19.2 (3.1) 5.6 (1.0) 37.8 (4.5)
57.4 (11.4) 3.6 (3.4) 7.7 (5.5) 31.3 (9.2) 82.3 (6.7) 15.9 (3.9) 11.6 (4.4) 36.3 (7.9)
GFR, glomerular filtration rate. Data are mean or percent prevalence (standard error). a < P 0.001 for a difference between the three groups. Obesity defined as body mass index ≥30 kg/m2 .
high prevalence of these urinary abnormalities was determined by cross-tabulation covariates with microalbuminuria and macroalbuminuria. RESULTS Table 1 outlines the clinical characteristics of individuals with or without albuminuria. Overall, 6.0% of subjects had microalbuminuria, and 0.7% had macroalbuminuria. Significant differences in the prevalence of albuminuria were present according to obesity, hypertension (treated and untreated), glucose metabolism, hypercholesterolemia, ischemic heart disease, cerebrovascular disease, and impaired glomerular filtration rate. Of the 6.0% of the population with microalbuminuria, the majority had hypertension, abnormal glucose metabolism, or both. Sixty-three percent of microalbuminuria was found in subjects with hypertension: 21.6% in those with hypertension alone, and 41.4% in those with hypertension and abnormal glucose metabolism; 52.5% of microalbuminuria was found in those with abnormal glucose metabolism: 26.1% in those with diabetes mellitus, 19.6% in those with impaired glucose tolerance, and 6.8% in those with impaired fasting glucose. In the participants with known diabetes mellitus, micro- and macroalbuminuria was present in 24.9% and 4.6%, respectively, whereas in those in whom diabetes mellitus was newly diagnosed as a result of the survey, 15.9% and 1.3% had micro- and macroalbuminuria, respectively. Of all participants with microalbuminuria, 25.9% had normal blood pressure and glucose metabolism, and in this group, alternative associations of microalbuminuria included obesity
S-23
in 13.5%, current smoking in 20.7%, and low glomerular filtration rate in 12.3%. Of those with macroalbuminuria, 78% were hypertensive, and 43% had abnormal glucose metabolism.
DISCUSSION This study confirms and extends previous findings documenting the prevalence of albuminuria in a large population-based cohort. The majority of cases of albuminuria were found within identifiable subgroups of the cohort. Two thirds of microalbuminuria was found in association with hypertension. Half of all cases of microalbuminuria were seen in subjects with abnormal glucose metabolism, and a similar percentage of all cases were found in subjects over 65 years of age. This information has implications at several levels of health care. From the general practitioner’s perspective, the patients found to have albuminuria at an annual check-up have a 60% probability of having hypertension. In addition, the patient has a 50% probability of having abnormal glucose metabolism, and testing for this should be considered. From a therapeutic perspective, drugs that target the renin-angiotensin pathway are known to be effective in improving renal and cardiovascular outcomes for patients with albuminuria in the setting of hypertension or abnormal glucose metabolism [8–12]—the subgroups of the population in which over 75% of cases of albuminuria reside. At a population level, screening all hypertensive individuals in the general population would identify 63.7% of cases of microalbuminuria. The AusDiab data carry significant messages about disease awareness and therapy in the community. For every subject known to have diabetes mellitus, another with previously undiagnosed diabetes mellitus was detected by fasting plasma glucose or oral glucose tolerance testing [13]. For every subject on treatment for hypertension, another was found with either undiagnosed or untreated hypertension. Thus, in the Australian community, at least, significant underdetection and consequent undertreatment of diabetes mellitus, hypertension, and proteinuria are prevalent. This situation is unlikely to be different in other communities. Appropriate identification and treatment of such individuals may have a dramatic impact on population trends in the burden of renal and cardiovascular disease.
CONCLUSION Microalbuminuria is present in a small percentage of the general population, but is highly prevalent among those with hypertension and abnormal glucose metabolism.
S-24
Atkins et al: Prevalence of albuminuria
ACKNOWLEDGMENTS We wish to thank the participants and the AusDiab Survey Team and Steering Committee. The AusDiab Study was supported by the Commonwealth Department of Health and Aged Care, State Governments of Queensland, South Australia, Tasmania, Western Australia, and Victoria and Territory Health Services, the Australian Kidney Foundation, Diabetes Australia (Northern Territory), the International Diabetes Institute, Eli Lilly (Australia), Janssen-Cilag (Australia), Knoll Australia, Merck Lipha s.a. Alphapharm, Merck Sharp & Dohme (Australia), Pharmacia and Upjohn, Roche Diagnostics, Servier Laboratories (Australia), SmithKline Beecham International, BioRad Laboratories, HITECH Pathology, and Qantas Airways. Reprint requests to Professor Robert Atkins, Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, 168, Australia. E-mail: [email protected]
REFERENCES 1. DAMSGAARD EM, FROLAND A, JORGENSEN OD, MORGENSEN CE: Microalbuminuria as a predictor of increased mortality in elderly people. BMJ 300:297–300, 1990 2. YUDKIN JS, FORREST RD, JACKSON CA: Microalbuminuria as a predictor of vascular disease in non-diabetic subjects. Lancet 2:530–533, 1988 3. MOGENSEN CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310:356– 360, 1984
4. MOGENSEN CE: Microalbuminuria as a predictor of clinical diabetic nephropathy. Kidney Int 31:673–689, 1987 5. DAMSGAARD EM, FROLAND A, JORGENSEN OD, MORGENSEN CE: Eight to nine year mortality in known non-insulin dependent diabetics and controls. Kidney Int 41:731–735, 1992 6. DUNSTAN DW, ZIMMET PZ, WELLBORN TA, et al: The Australian Diabetes, Obesity and Lifestyle Study (AusDiab)—Methods and response rates. Diab Res Clin Prac 57:119–129, 2002 7. AMERICAN DIABETES ASSOCIATION: Standards of medical care for patients with diabetes mellitus. Diabetes Care 23(Suppl 1):S32–42, 2000 8. PARVING HH, LEHNERT H, BROCHNER-MORTENSEN J, et al: The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345:870–878, 2001 9. LEWIS EJ, HUNSICKER LG, BAIN RP, ROHDE RD: The effect of angiotensin converting enzyme inhibition on diabetic nephropathy. N Engl J Med 329:1456–1462, 1993 10. JAFAR TH, SCHMID CH, LANDA M, et al: Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med 135:73–87, 2001 11. LEWIS EJ, HUNSICKER LG, CLARKE WR, et al: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860, 2001 12. BRENNER BM, COOPER ME, DE ZEEUW D, et al: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869, 2001 13. DUNSTAN DW, ZIMMET PZ, WELLBORN TA, et al: The rising prevalence of diabetes and impaired glucose tolerance—The Australian Diabetes, Obestity and Lifestyle Study. Diabetes Care 25:829–834, 2002