KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease    American Journal of Kidney Diseases  Volume 49, Issue 2, Pages S12-S154 (February 2007) DOI: 10.1053/j.ajkd.2006.12.005 Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 Percentage of patients in each group of the Steno Study who reached the intensive-treatment goals at a mean of 7.8 years. Abbreviation: BP, blood pressure. Reprinted with permission.45 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 2 Annual transition rates with 95% confidence intervals through the stages of nephropathy and to death from any cause. Reprinted with permission.41 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 3 CVD outcomes by treatment assignment in DCCT/EDIC. (A) Cumulative incidence of the first of any of the predefined CVD outcomes. (B) First occurrence of nonfatal myocardial infarction, stroke, or death from CVD. Compared with conventional treatment, intensive treatment reduced the risk of (A) any predefined CVD outcome by 42% (95% CI, 9% to 63%; P = 0.02) and (B) first occurrence of nonfatal myocardial infarction, stroke, or death from CVD by 57% (95% CI, 12% to 79%; P = 0.02). Reprinted with permission.115 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 4 Diabetes amplifies the CKD and CVD paradigm. Abbreviations: CAD, coronary artery disease; LVH, left ventricular hypertrophy; HTN, hypertension. American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 5 Cumulative incidence estimate of the combined primary end point for placebo and atorvastatin treatment groups in the 4D. Solid line: placebo; dotted line: atorvastatin treatment. Reprinted with permission.100 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 6 Screening for microalbuminuria. Reprinted with permission.35 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 7 Receiver operator characteristic (ROC) curve of the probability that the presence of diabetic retinopathy is predictive of patients who have biopsy/histology-proven diabetic glomerulopathy. Each ellipse represents an individual study, for which the height and width of the ellipse is representative of the inverse variance of the sensitivity and specificity, respectively.147,251,253-262 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 8 Cumulative incidence of urinary albumin excretion of 300 mg/24 h or greater (dashed line) and 40 mg/24 h or greater (solid line) in patients with type 1 diabetes mellitus receiving intensive or conventional therapy. (A) In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk of microalbuminuria by 34% (P < 0.04). (B) In the secondary-intervention cohort, patients with urinary albumin excretion of 40 mg/24 h or greater at baseline were excluded from the analysis of the development of microalbuminuria. Intensive therapy reduced the adjusted mean risk of albuminuria by 56% (P = 0.01) and the risk of microalbuminuria by 43% (P = 0.001) compared with conventional therapy. Reprinted with permission.132 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 9 Prevalence and cumulative incidence of microalbuminuria. Microalbuminuria defined as AER of 28 μg/min or greater, equivalent to 40 mg/24 h. (A) Prevalence at the end of the DCCT and during the EDIC Study. Differences between the 2 treatment groups are significant at each time after DCCT closeout (P < 0.001). (B) Cumulative incidence of new cases in the EDIC Study for participants in the intensive- and conventional-treatment groups with normal albuminuria at the beginning and end of the DCCT. The difference in cumulative incidences is significant by the log-rank test (P < 0.001). Reprinted with permission.133 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 10 Cumulative incidence of DKD after 6 years of follow-up in patients with type 2 diabetes treated by intensive (solid line) and conventional (dashed line) insulin injection therapy in the primary-prevention cohort of the Kumamoto study. Dropout patients are indicated by short vertical lines on the solid and dashed lines. Abbreviations: MIT, multiple insulin injection therapy group; CIT, conventional insulin injection therapy group. Reprinted with permission.136 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 11 Cumulative incidence of DKD after 8 years of follow-up in patients with type 2 diabetes treated by intensive (solid line) and conventional (dashed line) insulin injection therapy in the primary-prevention cohort of the Kumamoto study. Dropout patients are indicated by short vertical lines on the solid and dashed lines. Abbreviations: MIT, multiple insulin injection therapy group; CIT, conventional insulin injection therapy group. Reprinted with permission.137 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 12 Prevalence and incidence of albuminuria. Albuminuria was defined as AER of 208 μg/min or greater, equivalent to 300 mg/24 h. (A) Prevalence of clinical albuminuria at the end of the DCCT and during the EDIC Study. Differences between treatment groups are significant at each time point after DCCT close-out (P < 0.01). (B) Cumulative incidence of new cases in the EDIC Study for participants in the intensive- and conventional-treatment groups with either normoalbuminuria or microalbuminuria at the end of the DCCT. The difference in cumulative incidences is significant (P < 0.001). Reprinted with permission.133 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 13 Results from the CSG captopril trial. Changes in (A) blood pressure and (B) proteinuria. Squares, captopril group; circles, placebo group. Cumulative event rates for (C) doubling of baseline serum creatinine and (D) for death, dialysis, or transplantation. Modified with permission.168 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 14 Results from the IDNT. Kaplan-Meier curves of the percentage of patients with (A) the primary composite end point and its individual components, (B) a doubling of the serum creatinine concentration, (C) CKD stage 5, and (D) death from any cause. Reprinted with permission.169 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 15 Reduction of end points in type 2 diabetes with losartan in RENAAL. Kaplan-Meier curves of the percentage of patients with (A) the primary composite end point and its individual components, (B) a doubling of the serum creatinine concentration, (C) CKD stage 5, and (D) the combined end point of CKD stage 5 or death. Reprinted with permission.167 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 16 Systematic review of studies of DKD and non-DKD. The graph shows the change in blood pressure and proteinuria from baseline in trials that prospectively randomized various calcium antagonists and looked at either doubling of creatinine, CKD stage 5 and death, or rate of decrease in GFR. All studies used in this analysis also had a minimum of 1 year follow-up. Change in albuminuria was assessed in the context of outcomes of kidney disease. Abbreviations: DHP-CCB, dihydropyridine calcium channel blocker group; NDHP-CCB, nondihydropyridine calcium channel blocker group. Reprinted with permission.413 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 17 Meta-analysis of studies of DKD and non-DKD. Effects of blood pressure-lowering agents in DKD and non-DKD. Shown are the weighted mean results with 95% CIs for proteinuria (bars) and blood pressure (bold print) that were obtained in studies that compared the effects of an ACE inhibitor(ACEi) with that of another blood pressure–lowering agent. (Left) Results obtained with ACE inhibitors are shown subdivided to the type of kidney disease (nondiabetic [nonDM] and diabetic nephropathy [DM]). (Right) Results obtained with the comparator drugs. Abbreviation: Uprot, urinary protein; MAP, mean arterial pressure. Reprinted with permission.414 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 18 Blood pressure level and rate of GFR decline in controlled trials of DKD. Diamonds represent the mean achieved systolic blood pressure (SBP) and mean rate of calculated or directly measured GFR decline in the studies of DKD. Results not adjusted for other factors associated with rate of decline in GFR. The dotted line represents a flattening of possible benefit of blood pressure lowering at blood pressure levels less than 140 mm Hg. Abbreviation: HTN, hypertension. American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 19 Effect of pravastatin on the absolute risk reduction (ARR) of fatal coronary disease, nonfatal myocardial infarction, or coronary revascularization by CKD and diabetes (DM) status. Reprinted with permission.99 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 20 Median change in LDL-C concentrations from baseline until the end of the 4D. To convert values for LDL-C to mmol/L, multiply by 0.02586. Reprinted with permission.100 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 21 Meta-analysis demonstrating reduced risk of progression of DKD (loss of kidney function or increased albuminuria) by treatment with low-protein diets. Reprinted with permission.180 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 22 Effect of reduced dietary protein intake on CKD stage 5 and death in type 1 diabetes and CKD Stage 2 (inferred) at baseline. Reprinted with permission.181 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 23 Hazard ratios for CVD and heart failure end points as a function of percent change in 6-month albuminuria in the RENAAL trial. Relation is corrected for a series of risk markers. Abbreviation: CV, cardiovascular. Reprinted with permission.211 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 24 Hazard ratios for kidney end points (doubling of serum creatinine, CKD stage 5, or death) and CKD stage 5 as a function of percent change in 6-month albuminuria in the RENAAL trial. Relation is corrected for a series of risk markers. Abbreviation: ESRD, end-stage renal disease. Reprinted with permission.212 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 25 Kaplan-Meier analysis of kidney end points (doubling of serum creatinine [SCr], SCr level > 6 mg/dL, or CKD stage 5) by level of proteinuria change in the first 12 months of the IDNT. Reprinted with permission.210 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 26 Reduction of end points with intensive multifactorial therapy in the Steno 2 Study. Kaplan-Meier estimates of (A) the composite end point of death from cardiovascular causes, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease in the conventional-therapy group and intensive-therapy group and (B) relative risk (RR) of the development or progression of nephropathy, retinopathy, and autonomic and peripheral neuropathy during the average follow-up of 7.8 years in the intensive-therapy group compared with the conventional-therapy group. P in A was calculated with use of the log-rank test. The bars in A show standard errors. Abbreviation: CI, confidence interval. Reproduced with permission.45 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 27 Estimated number of adults with diabetes by age group and year for the developed and developing countries and for the world. Reprinted with permission.19 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

Figure 28 Adjusted incident rates of CKD stage 5 due to diabetes by race/ethnicity. Incident CKD stage 5 patients adjusted for age and gender. For Hispanic patients, we present data beginning in 1996, the first full year after the April 1995 introduction of the revised Medical Evidence form, which contains more specific questions on race and ethnicity. The data reported here have been supplied by the US Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the US government.4 American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10. 1053/j American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions

American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10. 1053/j American Journal of Kidney Diseases 2007 49, S12-S154DOI: (10.1053/j.ajkd.2006.12.005) Copyright © 2007 National Kidney Foundation, Inc. Terms and Conditions