# Presentation: 922512

## 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**

## 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

| GFR | >90 | 60-89 | 30-59 | 15-29 |
| --- | --- | --- | --- | --- |
| AA (%) | 79.2 | 17.4 | 3.1 | 0.25 |
| White (%) | 59.7 | 35.2 | 4.8 | 0.21 |

## Increasing Numbers of Patients May Overwhelm Nephrologists (amjkd,coresh 2003,nni 1999)

| Stage | Description | eGFR | Prevalence | Patients per Nephrologist |
| --- | --- | --- | --- | --- |
| 1 | Kidney damage with normal or increased GFR | 90 | 5,900,000 | 1180 |
| 2 | Mild decrease in GFR | 60-89 | 5,300,000 | 1060 |
| 3 | Moderate decrease in GFR | 30-59 | 7,600,000 | 1520 |
| 4 | Severe decrease in GFR | 15-29 |   400,000 | 80 |
| 5 | Kidney failure | <15 or dialysis |   350,000 | 70 |

## Five-Year Outcomes of CKD

| Stage of CKD | Patients on RRT (%) | Patient Deaths (%) |
| --- | --- | --- |
| 2 | 1.1 | 19.5 |
| 3 | 1.3 | 24.3 |
| 4 | 19.9 | 45.5 |

**RRT = renal replacement therapy.**
**Keith et al. *****Arch Intern Med*****. 2004;164:659-663. **

## Cardiovascular Disease (CVD) Is Linked to Chronic Kidney Disease (CKD)

- Cardiovascular Disease (CVD) Is Linked to Chronic Kidney Disease (CKD)

-        Relative Risk of CVD is 1.4 – 2.05 X with
-                      Creatinine  > 1.4 – 1.5 mg/dl
-         Relative Risk of CVD is 1.5 – 3.5 X with
-                      Microalbuminuria
-         Annual Mortality from CVD is 10 to 100-Fold Greater
-                        with Kidney Failure

- 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

- Proteinuria (albuminuria) results from injury to glomerular circulation
- Increased proteinuria (albuminuria) is associated with progressive kidney disease
- In diabetes and hypertension, proteinuria (albuminuria) is also an indicator of injury in the systemic circulation
- Proteinuria (albuminuria) is associated with increased cardiovascular risk

**Notes:**
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.

## 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**

**Notes:**
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.

## 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**

**Notes:**
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.

## 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

**Notes:**
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.

## Early Treatment Makes a Difference

**Notes:**
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.

## ACE Inhibitors, ARBs, and Combination Therapy in Nondiabetic Nephropathy

- Nakao et al. *Lancet.* 2003;361:117-124.

***P***** = 0.02**

## Features of Hypertensive Nephrosclerosis

- Long history of HTN, prior to known kidney dz.
- No other etiology for kidney disease.
- Proteinuria < 2.5 g/d. Urinalysis no cells.   No Diabetes.
- Evidence of other target organ damage-LVH,eye
- FH of HTN, high risk in African-Americans, age of onset of HTN- 25-45.
- Renal biopsy- hyalinization arterioles, intimal thick. small arteries, glom ischemia, fibrosis tubules

## 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

- African Americans: Addition of a Diuretic to ARB Therapy (N=440)

**Change in systolic BP**** (mm Hg)**

**Notes:**
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.

## 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**

**Notes:**
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.

## African American Study of Kidney Disease and Hypertension (AASK) 

| Therapy: | Usual | Aggressive |
| --- | --- | --- |
| Goal MAP: | 102-107 mm Hg | 92 mm Hg |
| N = 217 | Amlodipine | Amlodipine |
| N = 436 | Ramipril | Ramipril |
| N = 441 | Metoprolol | Metoprolol |

- 1094 patients with HTN and CKD , 4 yr f/uGFR = 20-65 mL/min/1.73 m2
- Excluded DBP <95 mm Hg, DM, UP/Cr >2.5

- 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.

## AASK Study Questions

- Does very aggressive lowering of blood pressure result in slower decline in renal function in hypertensive renal disease?
- Does the type of antihypertensive agent used to initiate blood pressure lowering matter with regard to renal outcomes?

## 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**

## %

**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

- <date/time>

- Wright et al.  *JAMA.* 2002;288:2421-2431.

**Notes:**
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.

## 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.

**Notes:**
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 AT1 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.

## Slide 27

## 	METHODS

- Post hoc analysis of a randomized 3X2 factorial trial  (AASK).
**Outcomes:** 1) GFR slope – analyzed by single-slope mixed effects model  2) ESRD- Cox proportional hazards regression analysis
**Predictor variables:**  1) baseline proteinuria       2)  baseline GFR   3) initial change in proteinuria at 6 months

## Slide 29

## Slide 30

## Slide 31

## Six Month Change in Proteinuria from Baseline Predicts Outcome of Kidney Disease: Results from the AASK trial 

- 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

- Changes in low levels of proteinuria (microalbuminuria) are predictive of ESRD in nondiabetic kidney disease.
- 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.

## Metabolic Syndrome and CKD

**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).**
**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)*****.**

## OBJECTIVE

**Does Metabolic Syndrome predict the rate of CKD progression to ESRD in African-Americans with Hypertensive Renal Disease??**

## African American Study of Kidney Disease and Hypertension (AASK) 

| Therapy: | Usual | Aggressive |
| --- | --- | --- |
| Goal MAP: | 102-107 mm Hg | 92 mm Hg |
| N = 217 | Amlodipine | Amlodipine |
| N = 436 | Ramipril | Ramipril |
| N = 441 | Metoprolol | Metoprolol |

- 1094 patients with HTN and CKD , 4 yr f/uGFR = 20-65 mL/min/1.73 m2
- Excluded DBP <95 mm Hg, DM or FBS>140, UP/Cr >2.5

- 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.

## METHODS

- _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):
**fasting plasma glucose**_**>**_**110 mg/dl**
-  **triglycerides**_**>**_** 150 mg/dl **
** ****HDL chol <40 mg/dl in men, < 50 mg/dl in women**
- BMI>30.
- Note:  **BP **_>_130/85 or on meds was present in all.

## ATP III: The Metabolic Syndrome**Diagnosis is established when  3 of these risk factors are present

**ATP III: The Metabolic Syndrome****Diagnosis is established when  3 of these risk factors are present

- Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

## METHODS

_**Outcome**_**:**  Time until the clinical composite outcome including: 50% or 25 ml/min/1.73m2 GFR decline (GFR event)-iothalamate, ESRD, or Death.
_**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.

## RESULTS

- 41% met criteria for metabolic syndrome using modified NCEP.
- 40.6% had BMI > 30 kg/m2 .
- None of the individual components of the MS predicted CKD progression in multivariate tests.

## Baseline Characteristics

| Variable | Total (n=1094) (SD) | MS + (n=208) | MS –
(n=634) | P value |
| --- | --- | --- | --- | --- |
| BMI | 30.6(6.5) | 33.5(6.2) | 28.6(6.1) | <.0001 |
| gluc | 94.9(18.5) | 105.2(21.5) | 91.4(15.7) | <.0001 |
| HDL | 48.3(16.1) | 40(12.2) | 54(15.6) | <.0001 |
| TRIG (n=842) | 140.5(81) | 186(95.6) | 107(48.4) | <.0001 |
| SBP | 150(23.8) | 148(23.3) | 151(24) | .15 |
| DBP | 95.5(14) | 95.6(14.3) | 95(24) | .65 |

## Cox Regression Analyses with Renal Outcomes

| Met. Syndrome
components | Multivariate HR(CI) | P value |  |  |
| --- | --- | --- | --- | --- |
| BMI>30 | 1.0(.78-1.3) | .95 |  |  |
| Glucose>110 | 1.14(.77-1.7) | .51 |  |  |
| HDL<40 | .95(.73-1.23) | .67 |  |  |
| TRIG>150 | 1.25(.96-1.62) | .09 |  |  |
| SBP>140 | 1.1(.83-1.5) | .48 |  |  |
| DBP>90 | 1.2(.87-1.62) | .28 |  |  |

## Modified NCEP with BMI

- 41% subjects meet criteria for metabolic syndrome.
- Cox model – unadjusted HR- 1.31 (1.02-1.67), p=.03 for MS with composite outcomes.
- Adjusted for all covariates except proteinuria- HR-1.37(1.06-1.77), p=.013.  With proteinuria- 1.23 (.95-1.58), p=.11.

## 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.

** **

## Cox regression analyses for ESRD alone, ESRD + death

- MS and ESRD alone, HR- 1.73( 1.2-2.5).
- MS and ESRD+death, HR- 1.62 (1.2-2.2).

## Cox Model for Metabolic Syndrome and Renal Outcomes

| Variable | HR | CI |
| --- | --- | --- |
| MS | 1.23 | .95-1.58 |
| Age | 1.01 | .78-1.31 |
| Males | .89 | .72-1.2 |
| smoker | 1.49 | 1.15-1.95 |
| alcohol | 1.11 | .84-1.46 |
| BUN | 1.0 | .72-1.39 |
| Cr | 1.78 | 1.3-2.8 |
| GFR | .61 | .37-.67 |
| Phos | 1.24 | .98-1.65 |
| Uric acid | .89 | .68-1.17 |
| UProt/Cr | 2.76 | 2.1-3.6 |

## Cox Model for Metabolic Syndrome and Renal Outcomes

| Variable | HR | CI |
| --- | --- | --- |
| MS | 1.37 | 1.07-1.77 |
| Age | 1.01 | .78-1.31 |
| Males | .94 | .72-1.2 |
| smoker | 1.49 | 1.15-1.95 |
| alcohol | 1.11 | .84-1.46 |
| BUN | 1.0 | .72-1.39 |
| Cr | 1.96 | 1.3-2.8 |
| GFR | .51 | .37-.67 |
| Phos | 1.27 | .98-1.65 |
| Uric acid | .89 | .68-1.17 |
|  |  |  |

## Kaplan Meier Survival Curve – Metabolic Syndrome status

## Strengths and Limitations

- Well-characterized population of African-Americans with CKD.
- Iothalamate GFR’s to assess renal function.
- No waist circumferences, but BMI used to assess obesity.
- 242 missing values- lack of triglycerides.

## SUMMARY

- African-Americans with CKD  in the AASK Study have a prevalence of metabolic syndrome (NCEP) of 41%.
- 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.
- 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.

## Conclusions

- This is the first prospective study reporting that metabolic syndrome predicts the rate of CKD progression.
- Further studies are needed to confirm this association and should include more specific measures of insulin resistance.
- 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.

## You Have The Power To Prevent Kidney Disease

## Perception of increased risk of CKD by patient characteristic as reported by primary care physicians

## Reducing Risks of Kidney Disease in African-Americans

- Education
- Early detection of kidney disease
- Adequate treatment of hypertension and diabetes
- Adequate access to healthcare
- Proper dietary habits
- More clinical research in African-Americans to better understand the increased risks