Recent advances in

management of
Diabetic Nephropathy
…Tiger by the tail
 Normal Kidney

Diabetic Kidney
 Diabetic nephropathy
 Diabetic nephropathy is progressive kidney disease
 Most common cause of ESRD

 More likely to die than progress to ESRD

 Multi-risk factor intervention is critical

 Lowering blood pressure with RAAS blockade is

critical
 Combinations of ACEi + ARB or MRA sensible

 No long term efficacy or safety data

 Prevent cardiovascular morbidity and mortality

 Why is Diabetic
Nephropathy Important?
Diabetes: The Most Common Cause
of ESRD
Primary Diagnosis for Patients Who Start Dialysis
Other Glomerulonephritis
10% 13% No. of patients
700 Projection
Diabetes Hypertension
No. of dialysis patients

27% 95% CI
600 50.1%
(thousands)

500
400
300 520,240
281,355
200
243,524
100 r2=99.8%
0
1984 1988 1992 1996 2000 2004 2008
United States Renal Data System. Annual data report. 2000.
 Cardiovascular Death is Major
Cause of Mortality in ESRD
Annual Cardiovascular Mortality (%)

100

ESRD Population GP Male

10
GP Female
GP Black
1
GP White
Dialysis Male
0.1 General Population
Dialysis Female

0.01 Dialysis Black

Dialysis White
0.001
25-34 35-44 45-54 55-64 65-74 75-84 > 85
Age (years)
Sarnak MJ and Levey AS. Am J Kidney Dis. 2000;35(4)(suppl1):S117-S131.
Foley RN. Am J Kidney Dis. 1998;32(S3):S112-119.
What is the Natural
History of Diabetic
Nephropathy?
 Definition of Diabetic
Nephropathy
 Clinical diagnosis based on Hx, Exam and urine
albumin/creatinine ratio in most cases
 Longstanding History of diabetes + retinopathy

 Macroalbuminuria (a.k.a “overt nephropathy”)

defined as random urine albumin/creatinine ratio
> 300 mg/g
 Hypertension (> 90%)

 Renal Biopsy confirmation is rare

Development of Macroalbuminuria Heralds Rapid Decline in
Glomerular Filtration in Type II Diabetes

Time ye a rs
1 1.5 2 2.5 3 3.5 4

-10
Cha nge in GFR ml/min

-20

-30
Microalbuminuria
-40
Macroalbuminuria

-50
Nelson RG. et al NEJM, 1996
 Diabetics with Nephropathy (DM/CKD) are More
Likely to Die than to Progress to ESRD
5% Medicare sample , 1996-1997 cohort, 2 year follow-up

N=1,045,263 188,596 33,586 19,335

100
Event Free
ESRD
80
Percent of Patients

All Cause
65.12 Death
73.18
60
85.04
90.53

40 5.85
2.25

20 0.31
0.07 29.04
24.57
9.40 14.65
0
NDM/Non-CKD DM/Non-CKD NDM/CKD DM/CKD
Status in the entry period
Diabetics with Macroalbuminuria are More Likely
to Die than Develop ESRD
The United Kingdom Prospective Diabetes Study (approx. 5000 Type 2 Diabetics)
Newly diagnosed, predominantly white, medically treated

1.4%
No albuminruia C
2.0% V
3.0%
Microalbuminruia
2.8% D
Macroalbuminruia
4.6%
E
A
2.3%
19%
T
Elevated Serum Creatinine H
Adler et al. Kid Int, 2003
What are Diabetics with Nephropathy
Dying From?
Myocardial Heart
Stroke
Infarction Failure

Sudden
Death
 Diabetic Nephropathy

Improving Outcomes
in Diabetic Nephropathy

Prevention of Prevention of
Cardiovascular End-Stage Renal Disease
Events
What is the Proper Therapy
of Kidney Disease in patients
with Diabetes?
 The Renal Injury Triad
Angiotensin II

Hypertension Proteinuria
 Definition of Abnormal Albuminuria
in Diabetes Mellitus
Microalbuminuria Macroalbuminuria
(Nephropathy)
Detected by dipstick No Yes

Urine Albumin / Cr 30 - 299 mg Alb / g Cr > 300 mg Alb / g Cr

Renal Risk Marker of future Marker progressive

nephropathy in some renal disease
Cardiovascular Risk Increased Increased
* Random (Spot) urine preferably A.M. recommended
 ADA Guidelines:
Diabetic Nephropathy
 A-Level Evidence (well done RCTs)
– To reduce the risk and/or slow the progression of
nephropathy, optimize glucose control.

– To reduce the risk and/or slow the progression of

nephropathy, optimize blood pressure control.
 ADA: Screening Guidelines
 Expert Consensus

– Perform an annual test for the presence of microalbuminuria in

(1) type 1 diabetic patients who have had diabetes >5 years and
(2) all type 2 diabetic patients starting at diagnosis.
– Acceptable samples to test for increased urinary albumin
excretion are timed (e.g., 12 or 24 h) collections for
measurement of albumin concentration and timed or untimed
samples for measurement of the albumin:creatinine ratio. For
screening, an untimed sample for albumin measurement (without
creatinine) may be considered if a concentration cutoff is used
that allows high sensitivity for detection of an increased albumin
excretion rate. Level of evidence: E
 ADA: Treatment Guidelines

 A-Level Evidence (well done trials)

— In the treatment of albuminuria/nephropathy both angiotensin-
converting enzyme (ACE) inhibitors and angiotensin receptor
blockers (ARBs) can be used:
— In hypertensive and nonhypertensive type 1 diabetic patients with
any degree of albuminuria, ACE inhibitors have been shown to
delay the progression of nephropathy. (1a)
— In hypertensive and non hypertensive type 2 diabetic patients with
microalbuminuria, ACE inhibitors and ARBs have been shown to
delay the progression to macroalbuminuria. (Cochrane 1a DOE)
— In patients with type 2 diabetes, hypertension, macroalbuminuria,
and renal insufficiency (serum creatinine >1.5 mg/dL), ARBs have
been shown to delay the progression of nephropathy.
— If one class is not tolerated, the other should be substituted.
 ADA: Treatment

 B-Level Evidence (well done cohort

studies)
— With the onset of overt nephropathy, initiate
protein restriction to <0.8 g • kg-1 body weight •
day-1 (approximately 10% of daily calories), the
current adult recommended daily allowance for
protein. Further restriction may be useful in
slowing the decline of glomerular filtration rate
in selected patients.
 ADA: Treatment

 Expert Consensus
— If ACE inhibitors or ARBs are used, monitor serum
potassium levels for the development of hyperkalemia.
— Consider referral to a physician experienced in the care
of diabetic renal disease when the glomerular filtration
rate has fallen to either <60 mL • min-1 • 173 m-2 or
difficulties have occurred in the management of
hypertension or hyperkalemia.
— Consider the use of non-dihydropyridine calcium
channel blockers or beta-blockers in patients unable to
tolerate ACE inhibitors or ARBs.
 ACE-I is More Renoprotective than Conventional
Therapy in Type 1 Diabetes (Total N = 409)
0
Captopril
% with 25 Conventional therapy
Doubling of 50
Baseline
Creatinine 75

100 Baseline creatinine > 1.5 mg/dl

0 1 2 3 4
-2–
- 40 –
0– P <.001
Decrease in - 20 –
Mean Blood- 2 – % Reduction 0 –
Pressure in
(mm Hg) - 4 – Proteinuria - 20 –
-6–
- 40 –
-8– NS - 60 –

Lewis et al. N Engl J Med. 1993;329:1456-1462.

 ARB (losartan) Reduces Risk of ESRD in
Diabetic Nephropathy
Reduction in Endpoints in NIDDM with Angiotensin Antagonist
Losartan (RENAAL) Trial: 1513 type 2 Diabetics with Nephropathy

Placebo
30 ESRD BP 142 / 74
Risk Reduction: 28% Losartan
% with event

p=0.002
20 BP 140 / 74

10
• Avg: 3.5 BP drugs/pt
• 90% in both groups
received a CCB
0
0 12 24 36 48
Months
P (+ CT) 762 715 610 347 42
L (+ CT) 751 714 625 375 69
Brenner et al. New Engl J. Med Sept 20 2001
 Irbesartan in Diabetic Nephropathy Trial:
Time to Doubling of Serum Creatinine, ESRD, or Death
1,715 Type 2 Diabetics with Nephropathy
70
Irbesartan
60 BP 140/77 RRR 23%
P=.006 RRR 20%
Amlodipine
P=NS P=.02
50 BP 141/77
Subjects (%)

Placebo
40 BP 144/80 Change in Proteinuria

5
30 0
-5

Percent Reduction
20 -10
-15 Irbesartan
Amlodipine
10 -20
Placebo
-25
-30
0 -35

0 6 12 18 24 30 36 42 48 54 60
Lewis EJ, et al. N Engl J Med. 2001;345:851-860. Follow-up
(mo)
 Albuminuria at Baseline Predicts ESRD in Type
2 Diabetics with Nephropathy: RENAAL Trial
(N=1513)

100

Baseline Albuminuria
% with ESRD end point
HR

80 ≥3.0 g/g
8.10

60

≥1.5<3.0 g/g
3.23
40

20 <1.5 g/g 1.0

0
0 12 24 36 48

de Zeeuw et al. Kid. Int. June 2004

Month
 Reduction in Proteinuria is Associated with Reduced
Risk for End-Stage Renal Disease in Diabetic
Nephropathy
4.0

3.5
Relative Risk for

3.0

2.5
ESRD

2.0

1.5

1.0

0.5

0.0
<-40 ≥-40 ≥-10 ≥10 ≥40 ≥60
<-10 <10 <40 <60
de Zeeuw et al. Kid. Int. June 2004 Change in Albuminuria %
 RENAAL; Proteinuria Reduction (<0%
versus >30%) determines the cardiovascular
outcome
CV Endpoint Heart Failure
40 <0% 40

>30%
% with CV endpoint

% with heart failure

30 30

20 20
<0%

10 10
>30%

0 0
0 12 24 36 48 0 12 24 36 48

Month Month
De Zeeuw et al; Circulation, in press
 Continuation of Losartan After Serum
Creatinine Doubles Reduces Incidence of
ESRD
80 Risk Reduction: 30%
% with ESRD event

p=0.013
60
P
40 L

20

0
0 6 12 18 24
Months
P (+CT) 198 111 48 11 4
L (+CT) 162 104 43 19 3
 RENAAL; Contribution of Baseline Systolic BP
or Proteinuria to ESRD in diabetic nephropathy

20 15.4
15.7 17.1
13.2
Hazard Ratio

15

10 5.5 6.7

5 2.4
1.8 2.0 3.6
1.4
0 1.0
1.6
>2.5
>165 0.9 1.1
1.25 - 2..5
165
151 - 1.0 .5 – 1.2
151
140 - <.5
<140
SBP Quartile at Proteinuria Quartile at
Baseline (mm Hg) Baseline (g/g)
unpublished
 Combination Therapy for BP Control:
Rule Rather Than Exception
Trial/Systolic Blood Pressure Achieved (mm Hg)

ALLHAT 138

IDNT 138
RENAAL 141

UKPDS 144
ABCD 132
MDRD 132
HOT 138
AASK 128
1 2 3 4
Number of BP Medications
Adapted from Bakris et al. Am J Kidney Dis. 2000;36:646-661.
 How I do get My Patient’s BP to the
Goal of <130 / < 80 mmHg?
 ACE Inhibitor / AII Receptor Antagonist
(maximum dose)
 Low ( 2 gram ) Sodium Diet
 Diuretic
 eGFR > 50 ml/min, thiazide
 eGFR < 50 ml/min, loop diuretic
 Long-Acting CCB or -blocker
 Long-acting -blocker vs clonidine
 Minoxidil
 Renal Effects of CCBs: Comparison
NDHP-CCBs show greater reductions in proteinuria in hypertensive
adults with proteinuria, with or without diabetes.

Proteinuria Systolic Blood Pressure

N=510 N=1,338
5 2%
0
-5
Change (%)

-10
-15 -13%
-20 -18.5%
-25
-30 NS
-30%
-35 DHP-CCB NDHP-CCB
P=0.01 Systematic Review of 28 Studies 17
Bakris GL et al. Kidney Int. 2004. In press.
Combination ACEi and Non-Dihydropyridine CCB
Reduces Proteinuria Further in Type 2 Diabetics
With Nephropathy
Trandolapril Verapamil SR Trandolapril (2.9 mg/d) +
5.5 mg/d 314 mg/d Verapamil SR (219 mg/d)

0
Percent reduction from baseline

-20

-40

-60 Proteinuria
Blood Pressure

Bakris, et al. Kid Int. 1998;54:1283.

 NKF Kidney Disease Outcomes Quality
Initiative: Pharmacologic Treatment
Type of CKD BP Goal Preferred Agents Other Agents to
for CKD, + HTN Reduce CVD
Risk and Reach
BP Goal

Diabetic < 130/80 ACEi or ARB Diuretic

Preferred, then -
Blocker or CCB

Non-Diabetic with Spot Urine Total Prot-to- < 130/80 ACEi or ARB Diuretic
Cr ratio > 200 mg/g Preferred, then -
Blocker or CCB

Non-diabetic with Spot Urine Total Prot-to- < 130/80 None Preferred Diuretic
Cr ratio < 200 mg/g Preferred, then
ACEi, ARB, B-
blocker or CCB

Transplanted < 130/80 None Preferred CCB, diuretic, -

KDOQI BP guidelines for CKD Am. J. Kid. Dis. Suppl. May 2004
CKD blocker ACEi,
ARB
Steno-2: Multiple Risk Factor Intervention Improves
Outcomes in Type 2 diabetics with
Microalbuminuria
 Randomized, open-label, target driven, long-term intensified
intervention trial aimed at multiple risk factors in patients with
type 2 diabetes and microalbuminuria
 BP < 130/80, (all treated with an ACEi or ARB)

 A1c < 6.5%

 Total Cholesterol < 175 mg/dl

 Total Triglyceride 150 mg/dl

 Aspirin 81 mg daily

 Exercise program

 Smoking Cessation

Gaede et al N.Engl.Med. 3448:383. 2003

Intensive Multi-risk Factor Intervention
Improves Outcomes in Type 2 Diabetes
Composite outcome: CV death, MI, coronary or
peripheral revascularization, CVA, amputation
60

Primary Composite End Point (%)

P=0.007

50
Conventional therapy

40

30

20
Intensive therapy
10

0
0 12 24 36 48 60 72 84 96
Months of Follow-up
No. at Risk
Conventional 80 72 70 63 59 50 44 41 13
therapy
Intensive 80 78 74 71 66 63 61 59 19
therapy
Gaede et al N.Engl.Med. 3448:383. 2003
Risk of Death after AMI is Reduced across all
Levels of Kidney Function with Recommended
Interventions
1 .2 0
1 .1 0 As pirin
1 .0 0 Be ta Bloc ke r
Hazard ratio

0 .9 0 ACE-I
0 .8 0
0 .7 0
0.61 0.62 0.58
0 .6 0
0.52 0.52
0 .5 0 0.45 0.44
0.40 0.41
0 .4 0
0 .3 0
0 .2 0
< 1 .5 1 .5 -2 .4 2 .5 -3 .9
Serum creatinine (mg/dl)

Shlipak et al., Ann Int Med 2002;137:555-62

 Diabetic Nephropathy:
Important Message
 Lower blood pressure < 130 / 80 mmHg
 Reducing Proteinuria

 Inhibition of Renin-Angiotensin System

 Multiple risk factor intervention

 Glycemia
 Dyslipidemia
 Physical activity
 Aspirin
 Smoking cessation
Is Combination Therapy With
An ACE Inhibitor And An ARB
Safe And Effective For Patients
With Diabetic Renal Disease?
 ACEi- or ARB-Based Regimens for
Diabetic Nephropathy Do Not Go Far
Enough!
50
Glomerular Filtration Rate

RAAS blockade + Other?

ml/min/1.73 m2

40
ACEi or ARB
ACEi + ARB
GFR = - 6 ml/min/yr
30 Time to ESRD 6.6 yrs
GFR = - ? ml/min/yr
Time to ESRD ?

20 No ACEi/ARB
or BP control
GFR = - 10 ml/min/yr
10 Time to ESRD 4 yrs

ESRD

2 4 6 8 10
Time (yrs)
 Combining an ACEi and an ARB is more
Renoprotective than Either Agent alone in Non-
Diabetic Nephropathy

Treatment N Baseline BP from Primary Hazard P value

BP mmHg baseline Endpoint Ratio**
mmHg*
Combinatio 85 130 / 75 5.2 / 2.9 10 (11%)* - -
n
Trandolapril 86 130 / 76 5.3 / 3.0 20 (23%) 0.40 0.016

Losartan 85 130 / 74 5.1 / 2.9 20 (23%) 0.38 0.018

*Average number of medications 3.2 per pt, 90% in all groups on dihydropyridine CCB
** Hazard Ratio comparing combination with either agent alone

Nakao et al. Lancet 361:117-124, 2003

 Summary of Studies combining ACEi and ARB in
Diabetic nephropathy: Effects on Proteinuria and
BP

DM Type Design N Duratio Intervention Results

n
1
Type 2 DRBCT 4 4 weeks 40 mg Lisinopril / No effect
50 Losartan
2
Type 2 DRBCT 18 8 weeks 8 mg candesartan 25% Prot and
BP
3
Type 1 DBRPCT 21 8 weeks 300 mg irbesartan 43% Prot and
BP
4
Type 1 DBRCT 20 8 weeks 20 mg Benazepril/ 15 % Prot and
ACEi / Valsartan 80 mg BP

5
Type 1 DBRCT 24 8 weeks 20 mg Enalapril/300 mg 25% Prot and
Irbesartan BP
1 Agarwal et al. Kid Int 59:2282, 2002; 2 Rossing et al. Diab Care. 25:95-100, 2002; 3 Jacobsen et al
Neph.6 Dial. Transplant 17:1019-1024, 2002;4 Jacobsen et al. J. Am. Soc. Neph. 14:992-999, 2003;5 Rossing
Type 2 DBRCT 20 8 weeks ACEi / Candsartan 16 mg
Et al. Kid Int 63:1874-80, 2003 ; 6 Rossing et al. Diab Care 26:2268-2274, 2003.
29% Prot
 Diabetic Nephropathy:
Important Message
 Small short-term studies suggest combinations of
ACEi and ARB reduce proteinuria synergistically
 Greater reductions in proteinuria with or without
additional lowering in blood pressure
 Hyperkalemia and Increased creatinine not well
documented
 Safety and Efficacy of combination ACEi and ARB in
diabetic with nephropathy not well established
Is There a Role for Spironolactone
(or Eplerenone) in Combination
with Other Drugs in Patients with
Diabetic Nephropathy?
 Role of Aldosterone in the Pathogenesis
of Diabetic Nephropathy
Hemodynamic Angiotensin II Non-Hemodynamic

Glomerular Hypertension Capillary wall injury

Aldosterone Inflammation
O2- , TGF-1 / PAI-1

Proteinuria

Injury to Glomerular Cells Sclerosis and

Fibrosis

Glomerular and Tubular Scarring Progressive

Renal Failure
 Adverse Renal and Cardiovascular
Effects of Aldosterone

Aldosterone

Glomerulosclerosis Ventricular Hypertrophy Endothelial dysfunction

Interstitial Fibrosis Cardiac Fibrosis
Proteinuria Inflammation
Contractile Dysfunction
Renal Failure Heart Failure Oxidative Stress
 Mineralocorticoid Receptor Blockade Improves
Cardiac Outcomes: Placebo Controlled Trials

Eplerenone reduces sudden cardiac death Spironolactone improves survival in

Post myocardial infarction Chronic Heart Failure
Cumulative Incidence of (%)

10
P=0.03 1.00
9 RR=0.79 (95% Cl, 0.64-0.97) Placebo P=0.001
0.95

Probability of Survival
8 RR=0.70 (95% Cl, 0.60-0.82
0.90
7
0.85
6 Eplerenone
0.80
5
0.75
4
0.70 Spironolactone
3
0.65
2
0.60
1
0.55 Placebo
0
0 3 6 9 12 15 18 21 24 27 30 33 36 0.50
0.45
Months since Randomization 0.00
0 3 6 9 12 15 18 21 24 27 30 33 36
Months
Can Dual Blockade of the RAAS Improve
Renal Outcomes in Diabetic Nephropathy?
Ang I

ACE Non-ACE
Pathways
Ang II
ACEi
ARB
+
AT1 Receptor

Aldosterone
+ Renal Injury MRA
and Proteinuria

Progressive Diabetic Nephropathy

 Study Design and
Objectives
 Study Design: Randomized double-blind placebo controlled
trial
 Study Population: Diabetics with macroalbuminuria despite
maximally dosed ACE inhibitor
 Intervention: Lisinopril 80 mg/d + losartan 100 mg/d or +
Aldactone 25 mg/d or + placebo
 Primary Outcome: Change in albuminuria
 Secondary Outcomes: Safety especially serum creatinine and
hyperkalemia
 Follow up: 52 weeks
 Study Hypothesis
Blockade of the renin-angiotensin system beyond ACE
inhibition decreases proteinuria and slows progression of
renal disease in diabetics with overt nephropathy by
suppressing aldosterone synthesis or blocking the
aldosterone receptor.
 Combined Inhibition of the RAAS Pathway: ACEi + ARB
vs ACEi + MRA in Diabetic Nephropathy

Diabetics with SBP > 130 mmHg

Scr < 3, female, < 4, male
Lisinopril 80 mg/d +
Urine albumin/Cr ratio > 300
Losartan 100 mg p.o qd
on ACE inhibitor + CT

Lisinopril 80 mg/d Lisinopril 80 mg/d + Placebo Maintain SBP 120-129 mmHg

With conventional D/C Study
antihypertensives Drug
Control to SBP < 130 Lisinopril 80 mg/d +
then Randomize Aldactone 25 mg p.o. qd

Run-in
Period

-4 -2 0 24-26
48- 52 56 ABPM, aldosterone
Kidney Function
ABPM, aldosterone
Kidney Function
ABPM, aldosterone
Kidney Function
Lipids, Inflammation Lipids, Inflammation Lipids, Inflammation

BP blood pressure, potassium and serum creatinine measurement

Time, weeks
RF renal function-GFR, RPF, 24 hour urine sodium, creatinine,potassium, protein and urea
 Diabetic Nephropathy:
Important Message
 Role for spironolactone or eplerenone in
diabetics with nephropathy not established
 Small, short-term studies suggest adding on
is efficacious for lowering proteinuria
 Not clear if combinations are safe in larger
population
 No long-term trials with cardiovascular or
renal endpoints
Beyond RAAS
Blockade
Hypothesis: Anemia is an Important
CV Risk Factor in Chronic Kidney
Disease
Chronic Kidney Anemia
Disease

Cardiovascular
disease
 Baseline Hemoglobin Predicts ESRD in
Type 2 Diabetics with Nephropathy:
RENAAL Trial (N=1513)
60
End-stage renal disease, %

50 Hb < 11.3*
Adjusted P
Hb g/dl
40 HR* value
Hb 11.4-12.5*
30 < 11.3 1.99 0.001
20 11.3-12.5 1.61 0.02
Hb 12.5-13.8*
10 12.5-13.8 1.85 0.002

0
Hb > 13.8 > 13.8 1.00 -
1 2 3 4 * Age, gender, GFR, Race, Proteinuria,
CV disease, A1c, lipids, BP, Ca, P, albumin
Time, years

Mohanram et al. Kid. Int. Sept 2004

 Is Anemia Causing
Cardiovascular And Renal
Disease In Diabetics, Or is it
Just A Marker?
 Trial to Reduce Cardiovascular Events
with Aranesp (Darbepoietin) Therapy
 Patient Population: 4000 Type 2 diabetics with Chronic
Kidney Disease (estimated GFR 20-60) and Hb < 11 g/dl
 Study Design: Randomized, double-blind, placebo-
controlled, multicenter international trial
 Intervention: Aranesp (darbepoetin alfa) to increase Hb to
11-13 g/dl
 Primary Outcome: time to all-cause mortality and
cardiovascular morbidity, including: myocardial infarction,
acute myocardial ischemia, congestive heart failure and
stroke
 Follow-up: 4 years

Funded by Amgen
 Diabetic Nephropathy: Some Novel
Therapies
Under Investigation
 Pirfenidone –antifibrotic agent

 Aliskerin anti-renin agent

 Robuxistaurin- Protein Kinase C Beta-1

antagonist
 Advanced Glycation Endproduct
antagonists
 Others
 How Should I Manage
My Patient With Diabetic
Nephropathy Today?
 Diabetic Nephropathy Management
Parameter Target
 Lower BP………………………
< 130/80 mmHg
 Block RAAS……………………

 Improve glycemia …………….

 Lower LDL cholesterol………..

 Anemia management ………... ACEi or ARB to max tolerated

 Endothelial protection………… A1c < 6.5% (Insulin/TZD)
 Smoking…………………

< 100 (70) mg/dl statin + other

Hb 11-12 g/dl (Epo + iron)

Aspirin daily
Cessation
 Diabetic Nephropathy: What
about proteinuria?
 Lower BP to goal with max dose ACEi or ARB

 Consider Adding: ACEi to ARB, mineralocorticoid

receptor antagonist to ACEi or ARB

 Calcium Channel Blockers

 Non-dihydropyridine

 Dihydropyridine
LOCKING THE STABLE DOOR
…after the horse has bolted

Thank You