Slide I-14 The pie chart shows that diabetes is currently the most common cause of ESRD. The lower graph reveals that the number of patients with ESRD maintained on dialysis is predicted to double over present levels by 2010, and the major contributor to this exponential increase is chronic renal failure associated with diabetes. United States Renal Data System. Annual data report. 2000. [Accessed on 25 April 2001] Available at URL: http://www.usrds.org/adr.htm.
The Dual Significance of Proteinuria Talking Points: In patients with proteinuric renal diseases the rate of progression of renal insufficiency is determined by the level of blood pressure and proteinuria. The reduction of blood pressure and proteinuria has a beneficial impact on renal risk. Observational studies have also demonstrated that proteinuria is a marker for systemic vascular injury. It is hoped that efforts to reduce proteinuria and control blood pressure will improve cardiovascular risk and reduce mortality. In this belief, the National Kidney Foundation and the American Diabetes Association have revised their recommendations for management of high-risk patients for tighter blood pressure control to <130/80. References: Agarwal R. Treatment of hypertension in patients with diabetes: lessons from recent trials. Cardiol Rev. 2001;9(1):36-44. Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, Tuttle K, Douglas J, Hsueh W, Sowers J. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36(3):646-661. Bianchi S, Bigazzi R, Campese VM. Microalbuminuria in essential hypertension: significance, pathophysiology, and therapeutic implications. Am J Kidney Dis. 1999;34(6):973-995. Keane WF. Proteinuria: its clinical importance and role in progressive renal disease. Am J Kidney Dis. 2000;35(4suppl1):S97-S105. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145-153.
Introduction This graph shows the adjusted hazard ratio for deciles of microalbuminuria as a risk for composite end point, cardiovascular mortality, all-cause mortality, stroke, and myocardial infarction in the nondiabetic subgroup. Key Talking Points This double-blind trial randomly assigned 8206 patients with stage II or III hypertension to losartan or atenolol The reference group for these hazard ratios are the patients in the first decile (those with a urine albumin–creatinine ratio <0.25 mg/mmol) The risk for the composite cardiovascular end point increases as albuminuria increases ( P <0.001) Reference Wachtell K, Ibsen H, Olsen MH, et al. Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study. Ann Intern Med. 2003;139:901-906. Transition to Next Slide In addition, proteinuria is a risk factor for the progression of CKD.
Points of Emphasis / Key Messages This figure, drawn from the composite endpoint of the LIFE study, depicts the positive correlation between increasing urinary A/C ratio in type 2 diabetic patients with comorbid HTN, and increasing CV hazard. Among diabetic hypertensive patients in this study , every 10-fold increase in urinary A/C ratio raised the risk of any event by 39%. These data were obtained from 1063 HTN patients with comorbid diabetes. The composite endpoint of CV risk referred to in the figure included CV mortality, all-cause mortality, stroke, and MI. Hazard ratio was adjusted for left ventricular mass by electrocardiography, age, sex, smoking, serum creatinine level, race, and study treatment allocation. Reference Wachtell K et al. Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: The LIFE study. Ann Intern Med. 2003;139:901-906.
Introduction This graph shows the doubling of SCr or ESRD by rate of urine protein excretion, showing proteinuria as a risk factor for CKD progression. Key Talking Points Jafar and colleagues performed a meta-analysis to evaluate the effect of ACEIs on the progression of kidney disease in patients with proteinuria. 1 Data were pooled from 11 randomized trials, all similar in study design and patient characteristics. These trials examined the effect of ACEIs on the progression of nondiabetic CKD. 1 Of the 1,860 patients enrolled, 187 had a doubling of SCr or ESRD. These patients were in the control group, and thus were not on ACEIs. 1 It was shown that patients with higher baseline urine protein excretion had a statistically significant increase in SCr as kidney disease progressed, as determined by the outcome of either doubling of SCr or ESRD. 1 This study defined the progression of renal disease as the combined end point of a doubling of baseline SCr or onset of ESRD. 1 Progression of renal disease is also characterized by change in eGFR, which has been shown to be a more sensitive measure of kidney function. 2 The authors concluded that a higher level of urine protein excretion, either at baseline or during treatment, is an independent risk factor for the progression of nondiabetic kidney disease, and that proteinuria should be considered a “modifiable” risk factor. 1 References 1. Jafar TH, Stark PC, Schmid CH, et al, for the AIPRD Study Group. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int. 2001;60:1131-1140. 2. Silkensen JR, Kasiske BL. Laboratory assessment of kidney disease: clearance, urinalysis, and kidney biopsy. In: Brenner BM, ed. Brenner & Rector’s The Kidney. 7th ed. Philadelphia, Pa: Saunders; 2004:1107-1150. Transition to Next Slide The reduction of proteinuria is associated with improved cardiovascular and renal outcomes.
With these effective therapies, early treatment makes a difference. Once kidney function begins to decrease, as demonstrated in this by the black line, on average without treatment it takes about 7 years before one reaches kidney failure. The red line demonstrates that if treatment begins when an individual has lost 50% of their kidney function, dialysis can be delayed on average by two years. That is that it would take on average 9 years before an individaul reaches kidney failure. With simple blood and urine testing that exists today, however, individuals can be identified even earlier, indicated by the gray line, add an additional 4 years on average to kidney failure free living. On average, healthcare costs for an individual on dialysis is $60 thousand a year. I am not a health economist, but by my calculation, by delaying CKD by 2 years that is 120 thousand for one individual. Diagnosing CKD at an early stage can add 2 or more years of ESRD-free survival. In some patients ESRD may actually be prevented. Careful attention to classic cardiovascular risk factors, especially smoking cessation and lipids, is also important to prevent premature cardiovascular death.
If a diuretic is used as a component of antihypertensive therapy in African Americans, the relative importance of renin in maintaining hemodynamic homeostasis is increased, and agents acting upon RAS are effective for treatment of hypertension when added to such therapy. Jamerson KA. Rationale for angiotensin II receptor blockers in patients with low-renin hypertension. Am J Kidney Dis. 2000;36:S24-S30.
It is likely that BP control will require more than one drug. The average number of antihypertensive medications required to achieve the lower target BP is 3.2, according to an analysis of the studies shown on this slide in which patients with either diabetes or renal impairment were randomly assigned to 2 different levels of BP reduction. Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis . 2000;36:646-661.
Amlodipine treatment arm was halted in September 2000. Patients from this arm were switched to open-label medication. Study was continued through the end of the trial. Amlodipine Treatment Arm Halted by NIH DSMB. DHP increases proteinuria. Proteinuria reduction not necessarily tied to BP reduction. BP went down with amlodipine: Amlodipine stopped due to increased proteinuria.
The mechanisms leading to renal failure are complex, but activation of RAS can play a major role by increasing systemic BP, by changing renal hemodynamics, and through direct effects on renal tissue. Increased systemic BP, coupled with constriction of efferent arterioles, can lead to glomerular hypertension and ultimately result in proteinuria and focal segmental glomerulosclerosis. Angiotensin II also increases sodium absorption at the level of the proximal tubule and may promote mesangial cell contraction and renal tubular hypertrophy. Glomerular injuries are characterized by mesangial cell overgrowth and excessive accumulation of extracellular matrix (ECM) proteins, resulting in occlusion of glomerular capillaries and ultimately progressing to renal failure. The nonhemodynamic effects of angiotensin II on mesangial cells may play a crucial role in development of glomerular injury. Angiotensin II, through stimulation of AT 1 receptors, induces the expression of the TGF- in mesangial cells. TGF- , in turn, promotes hypertrophy of mesangial cells, increased ECM production, and decreased ECM degradation through induction of PAI-1. As a result of these fibrotic changes, GFR falls and proteinuria increases. Increased rate of proteinuria may be toxic in itself and lead to further glomerulosclerosis. In animal models of renal failure, markers of fibrotic changes in the kidneys were significantly decreased by treatment with either an ACEI or an angiotensin receptor blocker. Border WA, Ruoslahti E. Transforming growth factor–beta in disease: the dark side of tissue repair. J Clin Invest. 1992;90:1-7. Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin II–mediated cardiovascular and renal disease. Pharmacol Rev. 2001;52:11-33.
Hypertensive Renal Disease in African-Americans Janice P. Lea, MD, MSc Associate Professor of Medicine Clinical Specialist in Hypertension Renal Division, Emory University
Diabetes and Hypertension: The Leading Causes of ESRD Primary Diagnosis For Patients Who Start Dialysis United States Renal Data System. Annual data report. 2000. 0 100 200 300 400 500 600 700 R 2 = 99.8% 243,524 281,355 520,240 Number of Dialysis Patients Diabetes 50.1% Hypertension 27% Glomerulonephritis 13% Other 10% No of Patients Projection 95% CI 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010
Stage 5 CKD Incidence Rates per Million Vary by Race/Ethnicity Odds ratios: 1 3.89 2.74 1.56 1 1.45 * P <0.0001 † Reference population. Data adjusted for age and gender from 2001 in United States Renal Data System. 2003 Annual Data Report. Available at: www.usrds.org. Incidence Rate per Million (2001)
NHANES III: Adjusted Odds of Reduced Kidney Function Coresh et al. Am J Kidney Dis. 41:1-12, 2003 0.21 4.8 35.2 59.7 White (%) 0.25 3.1 17.4 79.2 AA (%) 15-29 30-59 60-89 >90 GFR
Increasing Numbers of Patients May Overwhelm Nephrologists (amjkd,coresh 2003,nni 1999) 70 350,000 <15 or dialysis Kidney failure 5 80 400,000 15-29 Severe decrease in GFR 4 1520 7,600,000 30-59 Moderate decrease in GFR 3 1060 5,300,000 60-89 Mild decrease in GFR 2 1180 5,900,000 90 Kidney damage with normal or increased GFR 1 Patients per Nephrologist Prevalence eGFR Description Stage
Five-Year Outcomes of CKD RRT = renal replacement therapy. Keith et al. Arch Intern Med . 2004;164:659-663. 45.5 19.9 4 24.3 1.3 3 19.5 1.1 2 Patient Deaths (%) Patients on RRT (%) Stage of CKD
Cardiovascular Disease (CVD) Is Linked to Chronic Kidney Disease (CKD) <ul><li>Relative Risk of CVD is 1.4 – 2.05 X with </li></ul><ul><li>Creatinine > 1.4 – 1.5 mg/dl </li></ul><ul><li>Relative Risk of CVD is 1.5 – 3.5 X with </li></ul><ul><li>Microalbuminuria </li></ul><ul><li>Annual Mortality from CVD is 10 to 100-Fold Greater </li></ul><ul><li>with Kidney Failure </li></ul>Flack, et al. 1993 Levey, et al. 1998 Jensen, et al. 2000 Ruilope, et al. 2001 Mann, et al. 2001
Rates of Death and Cardiovascular Events in Patients According to GFR N = 1,120,295 adults. *Age-standardized rates per 100 person-years; † Cardiovascular event defined as hospitalization for coronary heart disease, heart failure, ischemic stroke, and peripheral arterial disease per 100 person-years. Go et al. N Engl J Med. 2004;351:1296-1305. eGFR (mL/min/1.73 m 2 )
The Dual Significance of Proteinuria <ul><li>Proteinuria (albuminuria) results from injury to glomerular circulation </li></ul><ul><ul><li>Increased proteinuria (albuminuria) is associated with progressive kidney disease </li></ul></ul><ul><li>In diabetes and hypertension, proteinuria (albuminuria) is also an indicator of injury in the systemic circulation </li></ul><ul><ul><li>Proteinuria (albuminuria) is associated with increased cardiovascular risk </li></ul></ul>
Proteinuria Is a Risk Factor for CVD Primary composite end-point: CV death, stroke, MI. Wachtell et al. Ann Intern Med . 2003;139:901-906. Comparison of lowest and highest decile of microalbuminuria in 7143 nondiabetic patients Adjusted Hazard Ratio
Microalbuminuria Predicts CV Risk at Levels Below Current Definition Wachtell K et al. Ann Intern Med. 2003;139:901-906. Microalbuminuria assessment in patients with hypertension and diabetes improves CV risk stratification Quintile of urine A/C ratio (mg/g) among 1,063 hypertension patients with diabetes 10 Microalbuminuria Normoalbuminuria Adjusted Hazard Ratio 0 0.5 1 1.5 2 2.5 <6.9 6.9 – <17.2 149.4 LIFE Study: Composite Endpoint 17.2 – <45.0 45.0 – <149.4
Proteinuria Is Also a Risk Factor for Progression of CKD % With Doubling of SCr or ESRD * P -values are for comparison across the subgroups. Jafar et al. Kidney Int. 2001;60:1131-1140. Urine Protein (g/d) P <.001* 0 10 20 30 40 50 <0.5 0.5-3.0 3.0-6.0 >6.0
ACE Inhibitors, ARBs, and Combination Therapy in Nondiabetic Nephropathy Primary end point: doubling of SCr or kidney failure. Nakao et al. Lancet. 2003;361:117-124. P = 0.02 * Combination* (n = 88) Losartan (n = 89) Trandolapril (n = 86)
Features of Hypertensive Nephrosclerosis <ul><li>Long history of HTN, prior to known kidney dz. </li></ul><ul><li>No other etiology for kidney disease. </li></ul><ul><li>Proteinuria < 2.5 g/d. Urinalysis no cells. No Diabetes. </li></ul><ul><li>Evidence of other target organ damage-LVH,eye </li></ul><ul><li>FH of HTN, high risk in African-Americans, age of onset of HTN- 25-45. </li></ul><ul><li>Renal biopsy- hyalinization arterioles, intimal thick. small arteries, glom ischemia, fibrosis tubules </li></ul>
Treatment of Hypertension in Nondiabetic Kidney Disease http://www.kidney.org/professionals/kdoqi/guidelines_bp
African Americans: Addition of a Diuretic to ARB Therapy (N=440) * P 0.01 vs placebo. † P 0.05 vs placebo. Clin. Therapeutics, 2001 Change in systolic BP (mm Hg) † * * * * *
Average Number of Antihypertensive Agents Needed Per Patient to Achieve Diastolic BP Goals Bakris et al. Am J Kidney Dis . 2000;36:646. 1 1.5 2 2.5 3 3.5 4 AASK (<92 mm Hg MAP) HOT (<80 mm Hg Diastolic) MDRD (<92 mm Hg MAP) ABCD (<75 mm Hg Diastolic) UKPDS (<85 mm Hg Diastolic) No. of BP medications
African American Study of Kidney Disease and Hypertension (AASK) <ul><li>1094 patients with HTN and CKD , 4 yr f/u GFR = 20-65 mL/min/1.73 m 2 </li></ul><ul><li>Excluded DBP <95 mm Hg, DM, UP/Cr >2.5 </li></ul>MAP = mean arterial pressure; DBP = diastolic blood pressure; UP/Cr = urinary protein to creatinine ratio. Wright et al for the AASK Study Group. JAMA. 2002;288:2421-2431. Aggressive Usual Therapy: Metoprolol Metoprolol N = 441 Ramipril Ramipril N = 436 Amlodipine Amlodipine N = 217 92 mm Hg 102-107 mm Hg Goal MAP:
AASK Study Questions <ul><li>Does very aggressive lowering of blood pressure result in slower decline in renal function in hypertensive renal disease? </li></ul><ul><li>Does the type of antihypertensive agent used to initiate blood pressure lowering matter with regard to renal outcomes? </li></ul>
Baseline Characteristics (2) 0.63 1.11 0.44 0.72 31.8 0.57 0.99 0.38 0.73 32.7 0.61 1.01 0.41 .75 33.0 Urine Protein (g/d) Male Female % with UP/Cr > 0.22 2.14 0.75 1.80 0.55 2.28 0.83 1.74 0.55 2.18 0.74 1.76 0.59 Serum Creatinine (mg/dL) Male Female Metoprolol N=441 Amlodipine N=217 Ramipril N=436 Mean SD or %. No significant differences among drug groups.
Clinical Evidence for Risk Reduction With ACE Inhibitor or Blockade: AASK Patients with existing kidney damage (baseline UP/Cr >0.22). Wright et al for the AASK Study Group. JAMA. 2002;288:2421-2431. Ramipril vs Amlodipine P = 0.004 Ramipril vs Metoprolol P = 0.04 Metoprolol vs Amlodipine P = 0.17 -38 -22 -20 Composite risk of rapid GFR decline-decrease from baseline of 50% or 25 mL/min/1.73 m 2 , kidney failure, or death
Percent Change in Proteinuria from Baseline Geometric mean urine protein/creatinine ratio declined faster in ramipril and metoprolol groups than amlodipine group (p < 0.001) % Change (SE) -33 -18 0 22 49 82 122 172 Follow-up Month 0 6 12 18 24 30 36 42 48 Metoprolol Ramipril Amlodipine
% of Patients Reached Urine Protein/Creatinine Ratio>0.22 During Follow-up by Drug Group Ramipril vs. Metoprolol: p=0.014 Amlodipine vs. Metoprolol: p=0.009 Ramipril vs. Amlodipine: p<0.001 % w i t h E v e n t s 0 10 20 30 40 50 60 Follow-up Month 0 6 12 18 24 30 36 42 48 54 60 Analysis of patients with UP/Cr < 0.22 at baseline Metoprolol Ramipril Amlodipine
African American Study of Kidney Disease and Hypertension (AASK) Trial Wright et al. JAMA. 2002;288:2421-2431. Amlodipine Treatment Arm Proteinuric patients progressed more rapidly to a renal event In patients with baseline urinary protein/creatinine ratio >0.22 (≈ baseline protein >300 mg/d) Ramipril Treatment Arm Metoprolol Treatment Arm The AASK trial, like other studies, confirms that amlodipine is associated with increases in proteinuria
Role of Angiotensin II in Renal Disease Pathways Ang II Efferent constriction PG, NO Afferent dilation Glomerular hypertension Proteinuria Hypertension TGF- Extracellular matrix Interstitial fibrosis PG = prostaglandin; NO = nitric oxide. Focal segmental glomerulosclerosis
METHODS <ul><li>Post hoc analysis of a randomized 3X2 factorial trial (AASK). </li></ul><ul><li>Outcomes: 1) GFR slope – analyzed by single-slope mixed effects model 2) ESRD - Cox proportional hazards regression analysis </li></ul><ul><li>Predictor variables: 1) baseline proteinuria 2) baseline GFR 3) initial change in proteinuria at 6 months </li></ul>
Lea J et.al. Arch Intern Med. 2005;165:947 Six Month Change in Proteinuria from Baseline Predicts Outcome of Kidney Disease: Results from the AASK trial 4.0 2.0 1.0 0.5 0.25 >-50% 0.125 >-50% to 20% - 20% to +25% +25% to 100% >+100% Relative Risk of ESRD
Conclusions <ul><li>Changes in low levels of proteinuria ( microalbuminuria ) are predictive of ESRD in nondiabetic kidney disease. </li></ul><ul><li>The association of early changes in proteinuria with subsequent renal outcomes suggests that effects of antihypertensive agents on proteinuria should be considered when selecting agents for their potential to slow renal disease progression. </li></ul>
Metabolic Syndrome and CKD <ul><li>The metabolic syndrome is independently associated with an increased risk for incident CKD in nondiabetic adults in a prospective study – ARIC (Chertow et al, JASN 2005). </li></ul><ul><li>Metabolic syndrome is a strong and independent risk factor for chronic kidney disease in a cross-sectional analyses of 6217 subjects from NHANES. The multivariate adjusted OR of CKD in subjects with MS was 2.6 compared to those without MS (Chen et al, Ann. Intern. Med. 2004) . </li></ul>
OBJECTIVE <ul><li>Does Metabolic Syndrome predict the rate of CKD progression to ESRD in African-Americans with Hypertensive Renal Disease?? </li></ul>
African American Study of Kidney Disease and Hypertension (AASK) <ul><li>1094 patients with HTN and CKD , 4 yr f/u GFR = 20-65 mL/min/1.73 m 2 </li></ul><ul><li>Excluded DBP <95 mm Hg, DM or FBS>140 , UP/Cr >2.5 </li></ul>MAP = mean arterial pressure; DBP = diastolic blood pressure; UP/Cr = urinary protein to creatinine ratio. Wright et al for the AASK Study Group. JAMA. 2002;288:2421-2431. Aggressive Usual Therapy: Metoprolol Metoprolol N = 441 Ramipril Ramipril N = 436 Amlodipine Amlodipine N = 217 92 mm Hg 102-107 mm Hg Goal MAP:
METHODS <ul><li>Predictor variables: individual and composite components of the metabolic syndrome at baseline defined by the presence of any two of the following in addition to hypertension (NCEP): </li></ul><ul><ul><li>fasting plasma glucose > 110 mg/dl </li></ul></ul><ul><ul><li>triglycerides > 150 mg/dl </li></ul></ul><ul><ul><li>HDL chol <40 mg/dl in men, < 50 mg/dl in women </li></ul></ul><ul><ul><li>BMI>30. </li></ul></ul><ul><ul><li>Note: BP > 130/85 or on meds was present in all. </li></ul></ul>
ATP III: The Metabolic Syndrome* * Diagnosis is established when 3 of these risk factors are present Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. < 40 mg/dL < 50 mg/dL Men Women > 102 cm (> 40 in) > 88 cm (> 35 in) Men Women 110 mg/dL Fasting glucose 130/ 85 mm Hg Blood pressure HDL-C 150 mg/dL TG Abdominal obesity† (Waist circumference‡) Defining Level Risk Factor
METHODS <ul><li>Outcome : Time until the clinical composite outcome including: 50% or 25 ml/min/1.73m 2 GFR decline (GFR event)-iothalamate, ESRD, or Death. </li></ul><ul><li>Statistical Analyses: Multivariable Cox Proportional Hazards Models run for the metabolic syndrome composite and for each covariate with the composite renal outcome with and without adjustments for covariates. </li></ul>
RESULTS <ul><li>41% met criteria for metabolic syndrome using modified NCEP. </li></ul><ul><li>40.6% had BMI > 30 kg/m 2 . </li></ul><ul><li>None of the individual components of the MS predicted CKD progression in multivariate tests. </li></ul>
Baseline Characteristics .65 95(24) 95.6(14.3) 95.5(14) DBP .15 151(24) 148(23.3) 150(23.8) SBP <.0001 107(48.4) 186(95.6) 140.5(81) TRIG (n=842) <.0001 54(15.6) 40(12.2) 48.3(16.1) HDL <.0001 91.4(15.7) 105.2(21.5) 94.9(18.5) gluc <.0001 28.6(6.1) 33.5(6.2) 30.6(6.5) BMI P value MS – (n=634) MS + (n=208) Total (n=1094) (SD) Variable
Modified NCEP with BMI <ul><li>41% subjects meet criteria for metabolic syndrome. </li></ul><ul><li>Cox model – unadjusted HR- 1.31 (1.02-1.67), p=.03 for MS with composite outcomes. </li></ul><ul><li>Adjusted for all covariates except proteinuria- HR-1.37(1.06-1.77), p=.013. With proteinuria- 1.23 (.95-1.58), p=.11. </li></ul>
TABLE 3: Hazard ratio of metabolic syndrome with Time to Event analyses with and without adjustments for significant covariates and BMI and adjusted for BP goal group and Antihypertensive Drug group. Hazard Ratio Confidence Interval P value MS unadjusted 1.31 1.03-1.68 .03 MS adjusted for other covariates, + uprot/cr 1.37 1.23 1.07-1.77 .95-1.58 .01 .11 By BP goal 1.37 1.05-1.8 .02 By Drug group 1.35 1.03-1.78 .03
Cox regression analyses for ESRD alone, ESRD + death <ul><li>MS and ESRD alone, HR- 1.73( 1.2-2.5). </li></ul><ul><li>MS and ESRD+death, HR- 1.62 (1.2-2.2). </li></ul>
Cox Model for Metabolic Syndrome and Renal Outcomes .95-1.58 1.23 MS 2.1-3.6 2.76 UProt/Cr .68-1.17 .89 Uric acid .98-1.65 1.24 Phos .37-.67 .61 GFR 1.3-2.8 1.78 Cr .72-1.39 1.0 BUN .84-1.46 1.11 alcohol 1.15-1.95 1.49 smoker .72-1.2 .89 Males .78-1.31 1.01 Age CI HR Variable
Cox Model for Metabolic Syndrome and Renal Outcomes 1.07-1.77 1.37 MS .68-1.17 .89 Uric acid .98-1.65 1.27 Phos .37-.67 .51 GFR 1.3-2.8 1.96 Cr .72-1.39 1.0 BUN .84-1.46 1.11 alcohol 1.15-1.95 1.49 smoker .72-1.2 .94 Males .78-1.31 1.01 Age CI HR Variable
Kaplan Meier Survival Curve – Metabolic Syndrome status
Strengths and Limitations <ul><li>Well-characterized population of African-Americans with CKD. </li></ul><ul><li>Iothalamate GFR’s to assess renal function. </li></ul><ul><li>No waist circumferences, but BMI used to assess obesity. </li></ul><ul><li>242 missing values- lack of triglycerides. </li></ul>
SUMMARY <ul><ul><li>African-Americans with CKD in the AASK Study have a prevalence of metabolic syndrome (NCEP) of 41%. </li></ul></ul><ul><ul><li>African-Americans with hypertensive CKD and metabolic syndrome have a 37% higher risk of reaching the composite clinical endpoints of GFR decline, ESRD, or death. </li></ul></ul><ul><ul><li>These findings persisted after adjusting for other factors known to influence renal outcomes except for proteinuria and did include adjustments for BP goal group and antihypertensive therapy. </li></ul></ul>
Conclusions <ul><ul><li>This is the first prospective study reporting that metabolic syndrome predicts the rate of CKD progression. </li></ul></ul><ul><ul><li>Further studies are needed to confirm this association and should include more specific measures of insulin resistance. </li></ul></ul><ul><ul><li>Our findings may explain some of the variability observed in the progression to ESRD and may provide a new target for treating CKD in a high risk group. </li></ul></ul>
Perception of increased risk of CKD by patient characteristic as reported by primary care physicians
Reducing Risks of Kidney Disease in African-Americans <ul><li>Education </li></ul><ul><li>Early detection of kidney disease </li></ul><ul><li>Adequate treatment of hypertension and diabetes </li></ul><ul><li>Adequate access to healthcare </li></ul><ul><li>Proper dietary habits </li></ul><ul><li>More clinical research in African-Americans to better understand the increased risks </li></ul>