Guideline 1: goals of antihypertensive therapy in CKD   American Journal of Kidney Diseases  Volume 43, Pages 65-230 (May 2004) DOI: 10.1053/j.ajkd.2004.03.007

Fig 28 General approach to hypertension and use of antihypertensive agents in CKD. Diamonds indicate decisions. Rectangles indicate actions. Superscripts refer to items listed in Table 45. A more detailed approach to decision-making and protocols for action are given in later sections. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 29 Age-associated decline in estimated GFR in NHANES III. GFR estimated from serum creatinine using MDRD Study equation. Age ≥20, N = 15, 600. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 30 Evaluation for proteinuria for evaluation of hypertension and use of antihypertensive agents in CKD. Figure is modified from CKD Guideline 5, Fig 57, Fig 57 Rationale for combination of ARBs or ACE inhibitors with diuretics. Schematic depiction of additive antihypertensive effects of the combination of a diuretic and either an ACE inhibitor or an ARB. Volume loss produced by diuretic therapy activates the renin-angiotensin system, blunting the decline in blood pressure. Blockade by either ACE inhibitor or ARB increases the antihypertensive response. because criteria for selection of preferred agents in nondiabetic kidney disease are based on measurements of urine total protein rather than urine albumin.1 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 30 Evaluation for proteinuria for evaluation of hypertension and use of antihypertensive agents in CKD. Figure is modified from CKD Guideline 5, Fig 57, Fig 57 Rationale for combination of ARBs or ACE inhibitors with diuretics. Schematic depiction of additive antihypertensive effects of the combination of a diuretic and either an ACE inhibitor or an ARB. Volume loss produced by diuretic therapy activates the renin-angiotensin system, blunting the decline in blood pressure. Blockade by either ACE inhibitor or ARB increases the antihypertensive response. because criteria for selection of preferred agents in nondiabetic kidney disease are based on measurements of urine total protein rather than urine albumin.1 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 57 Rationale for combination of ARBs or ACE inhibitors with diuretics. Schematic depiction of additive antihypertensive effects of the combination of a diuretic and either an ACE inhibitor or an ARB. Volume loss produced by diuretic therapy activates the renin-angiotensin system, blunting the decline in blood pressure. Blockade by either ACE inhibitor or ARB increases the antihypertensive response. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 31 Evaluation of patients with CKD for treatment of hypertension and use of antihypertensive agents. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 32 Use of the score to estimate the probability of RAD. The vertical axis shows the predicted probability of renal artery stenosis in patients with drug-resistant hypertension as a function of the sum score. The sum score was derived from the prediction rule (Table 78). Thin (gray) lines represent 95% confidence intervals. Reproduced with permission.195 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 33 Mean change in SBP (mm Hg) from baseline in hypertensive participants of the DASH study during 8 weeks of intervention by diet assignments—DASH or control diets. Horizontal axis, weeks after dietary instruction; vertical axis, change in systolic blood pressure (mm Hg) from baseline. Figure modified and reprinted with permission.281a American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 34 Hypertension and antihypertensive agents in CKD. Superscripts refer to items in Table 89. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 35 Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack (ALLHAT) Trial. Mean systolic and diastolic blood pressure by year during follow-up. Number measured at 6 years for chlorthalidone, amlodipine, and lisinopril are 2,721, 1,656, and 1,551, respectively. Reprinted with permission.107 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 36 Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack (ALLHAT) Trial. Cumulative event rates for primary outcome (fatal coronary heart disease or nonfatal myocardial infarction) by treatment group. No significant difference was observed for amlodipine (relative risk [RR], 0.98; 95% confidence interval [CI], 0.90 to 1.07; P = 0.65) or lisinopril (RR, 0.99; 95% CI, 0.91 to 1.09; P = 0.81) versus chlorthalidone with a mean follow-up of 4.9 years. Reprinted with permission.107 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 37 Collaborative Study Group (CSG) Captopril Trial. Change in blood pressure (A) and proteinuria (B). (Squares) Captopril group; (circles) placebo group. Cumulative event rates for doubling of baseline serum creatinine (C) and for death, dialysis, or transplantation (D). Modified with permission.329 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 38 Irbesartan Diabetic Nephropathy Trial (IDNT). Kaplan-Meier curves of the percentage of patients with the primary composite end point (A) and its individual components, a doubling of the serum creatinine concentration (B), end-stage renal disease (C), and death from any cause (D). Reprinted with permission.139 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 39 Reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL). Kaplan-Meier curves of the percentage of patients with the primary composite end point (A) and its individual components, a doubling of the serum creatinine concentration (B), end-stage renal disease (C), and the combined end point of end-stage renal disease or death (D). Reprinted with permission.338 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 40 Meta-analysis of studies of diabetic and nondiabetic kidney disease. The left panel shows weighted mean results and 95% CIs for change in proteinuria in studies of antihypertensive agents. The effects of ACE inhibitors and nondihydropyridine calcium-channel blockers were significant. The right panel shows results of regression models. Coefficients are mean and 95% confidence interval for the change in proteinuria (%) for factors/number of studies. Only the effect of ACE inhibitors was significant. Reproduced with permission.431 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 41 Meta-analysis of studies of diabetic and nondiabetic kidney disease. Effects of blood pressure lowering agents in diabetic and nondiabetic renal disease. Depicted are the weighted mean results with 95% CIs for proteinuria (bars) and blood pressure (bold print) that have been obtained in studies that compared the effects of an ACE inhibitor to that of another blood-pressure lowering agent. On the left the results obtained with ACE inhibitors are shown subdivided to the type of renal disease (nondiabetic renal disease [nonDM] and diabetic nephropathy [DM]). Results obtained with the comparator drugs are given on the right. Reproduced with permission.432 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 42 Blood pressure level and rate of GFR decline in controlled trials of diabetic kidney disease. Diamonds represent the mean achieved systolic blood pressure and mean rate of calculated or directly measured GFR decline in the studies of diabetic kidney disease. Results not adjusted for other factors associated with rate of decline in GFR. The dotted line represents a flattening of possible benefit of BP lowering at BP levels below 140 mm Hg. Reproduced with permission.440 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 43 Hypertension and antihypertensive agents in diabetic kidney disease. Superscripts refer to items in Table 110. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 44 ACE Inhibition in Progressive Renal Disease (AIPRD) Study Group Pooled Analysis. Effects on blood pressure (A), urinary protein excretion (B), survival without kidney failure (C), or the combined outcome of doubling of baseline serum creatinine or kidney failure. Patients taking ACE inhibitors (dotted line) and controls (solid line). Follow-up measurements were reported more often during the first 2 years and less often thereafter. Mean blood pressure and mean urine protein excretion during follow-up were defined as the mean of all available follow-up values for each patient. Change during follow-up was defined as the baseline value minus the mean follow-up value for each patient. The number of patients with follow-up data available for analysis of survival without kidney failure is shown below the x-axis of (C). Reprinted with permission.458 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 45 ACE Inhibition in Progressive Renal Disease (AIPRD) Study Group Pooled Analysis. Relationship of baseline urinary protein to risk for kidney failure (A) or combined outcome of doubling of baseline serum creatinine or kidney failure (B), or relative risk for these outcomes (C and D). Patients taking ACE inhibitors (squares) and controls (circles). The values above the graphs in (A) and (B) are the fractions of patients with event in the control group (upper row) and ACE inhibitor group (lower row). Relative risks were calculated form multivariable models controlling for significant baseline patient and study characteristics. The solid horizontal line at a relative risk of 1.0 in (C) and (D) indicates no difference between the ACE inhibitor and control groups; the solid and dotted curved lines represent point estimates and 95% CI for the relative risks. P values for tests for interactions between baseline urinary protein excretion and treatment were 0.03 and 0.001, respectively. Reprinted with permission.458 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 46 African-American Study of Kidney Disease and Hypertension (AASK). Clinical composite events include declining GFR, kidney failure or death. Ramipril versus metoprolol (RR = 0.78, P = 0.042; metoprolol versus amlodipine (RR = 0.80, P = 0.17); ramipril versus amlodipine (RR = 0.62, P = 0.004). RR computed after adjustment for baseline covariates. Reproduced with permission.454 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 47 Modification of Diet in Renal Disease (MDRD) Study. Effect of strict blood pressure control on GFR decline. For Study A (baseline GFR 25 to 55 mL/min/1.73 m2), estimated mean (±SE) rates of decline in GFR from baseline to 3 years, based on a 2-slope model are shown. For Study B (baseline GFR 13 to 24 mL/min/1.73 m2), mean (±SE) rates of decline in GFR are estimated from the 1-slope informative censoring model. Closed circles designate the usual blood pressure group; open circles designate the low blood pressure group. The number in parentheses in each column is the total number of patients in both blood pressure groups who had a least one follow-up measurement. Greater baseline proteinuria is associated with a steeper mean GFR decline and with a greater benefit form the low blood pressure goal (P = 0.02 in Study A; P = 0.01 in Study B). Reprinted with permission.467 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 48 Modification of Diet in Renal Disease (MDRD) Study. Relationship between mean arterial blood pressure and GFR decline. Mean GFR decline and achieved follow-up blood pressure in the MDRD Study A (patients with baseline GFR 25 to 55 mL/min/1.73 m2). Regression lines relating the estimated mean GFR decline over 3 years to mean follow-up MAP for groups of patients defined according to baseline proteinuria. Within each group, a 3-slope model was used with break points at 92 and 98 mm Hg. Reprinted with permission.467 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 49 African-American Study of Kidney Disease and Hypertension (AASK). Effect of strict blood pressure control on events. Clinical composite event defined as declining GFR, kidney failure, or death. Mean achieved blood pressures of 141/85 mm Hg in the usual group and 127/78 mm Hg in the low group. Relative risk of low versus usual goal = 0.98 (0.79 to 1.22), P = 0.85. Reprinted with permission.454 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 50 ACE Inhibition and Progessive Renal Disease (AIPRD) Study Group Pooled Analysis. Relative risk for kidney disease progression based on levels of SBP and urinary protein excretion during follow-up. Filled and open symbols show the relative risk for patients with current urine protein excretion ≥1.0 g/d (n = 9,336 visits, 223 events) and <1.0 g/d (n = 13,274 visits, 88 events), respectively. Reference group for each is defined at SBP 110 to 119 mm Hg. Results are from a single multivariable model including two levels for urine protein excretion, six levels for SBP and interaction of current SBP and current urine protein excretion. Covariates include assignment to ACE inhibitor versus control group, gender, age, baseline SBP, baseline diastolic blood pressure, baseline urine protein excretion, baseline serum creatinine concentration (<2.0 or ≥2.0 mg/dL), interaction of baseline serum creatinine and baseline urine protein excretion, interaction of baseline serum creatinine and current urine protein excretion, and study terms. Reprinted with permission.471 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 51 Hypertension and antihypertensive agents in nondiabetic kidney disease. Superscripts refer to items in Table 118. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 52 Collaborative Transplant Study. Relationship between systolic blood pressure and graft survival. Association of SBP at end of year 1 with subsequent graft survival in recipients of cadaveric kidney transplants. Ranges of SBP values in mm Hg and number of patient studies in the subgroups are indicated. The association of SBP with graft survival at 7 years was statistically significant (P < 0.0001). American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 53 Hypertension and antihypertensive agents in kidney transplant recipients. Superscripts refer to items in Table 122. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 54 Physiology of the renin-angiotensin system and sites of action of ACE inhibitors and angiotensin-receptor blockers. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 55 Physiology of side-effects of ACE inhibitors. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 56 Determinants of diuretic response. Sodium excretion rate as a function of tubular delivery of diuretic. “A” represents pharmacokinetic determinants of diuretic response for an orally administered diuretic. The solid sigmoidal-shaped dose-response curve has three components: threshold (diuretic delivery rate sufficient to first produce a diuresis); efficiency (rate of delivery that produces an optimal response for any amount of diuretic entering the urine); and maximal response (urinary delivery of diuretic above which no additional diuretic response can occur). “B” represents altered pharmacodynamic determinants in “diuretic resistance,” in which the normal simoidal-shaped curve is shifted downwards and to the right. Diuretic delivery necessary to achieve a threshold response can vary substantially in diuretic resistance. American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 58 Blood pressure cuff dimensions. Dimensions of bladder and cuff in relation to arm circumference. A, ideal arm circumference; B, range of acceptable arm circumferences; C, bladder length; D, midline of bladder; E, bladder width; F, cuff width. Reproduced with permission.153 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 59 Determination of proper cuff size, step 1. The cuff bladder width should be approximately 40% of the circumference of the arm measured at a point midway between the olecranon and acromion. Reprinted with permission.568 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 60 Determination of proper cuff size, step 2. The cuff bladder should cover 80% to 100% of the circumference of the arm. Reprinted with permission.568 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)

Fig 61 Blood pressure measurement. Blood pressure should be measured with cubital fossa at heart level. The arm should be supported. The stethoscope bell is placed over the brachial artery pulse, proximal and medial to the cubital fossa, below the bottom edge of the cuff. Reprinted with permission.568 American Journal of Kidney Diseases 2004 43, 65-230DOI: (10.1053/j.ajkd.2004.03.007)