1. Dinkar Kaw, M.D., Division of Nephrology
Diabetic Nephropathy
Dinkar Kaw, M.D.,
Division of Nephrology

2. Objectives Prevalence of diabetic kidney disease
Pathogenesis of diabetic nephropathy
Clinical course of diabetic nephropathy
Slowing the progression of nephropathy
Screening for early nephropathy

3. Causes of End Stage Renal Disease
USRDS 1993 Annual Data Report

4. Diabetic Nephropathy The most common cause of ESRD in USA.
Accounts for nearly 40% of ESRD in USA. This proportion of ESRD due to DN is less in Europe than in USA.
Incidence is increasing, accounted for 10% in 1973 but now around 40% of USRD populations.
However one needs to keep in mind all diabetic patients with ESRD do not have DN as underlying cause of ESRD.

5. Diabetic Nephropathy
Mortality of ESRD patients with Diabetes Mellitus is higher than in ESRD patients without Diabetes.
This higher mortality is due to increase in Cardiovascular, cerebro-vascular, peripheral vascular and infection related morbidity.
In USA the health care cost for diabetic ESRD patients has approached to $ 2 billion per year.

6. Patient Survival on Dialysis by Cause of Renal Failure
From UpToDate v 6.2; Data from USRDS 1995 Annual Report

7. Diabetic Nephropathy
DN occurs in 35-40% of patients with type I diabetes (IDDM) whereas it occurs only in 15-20% of patients with type II diabetes (NIDDM).
More frequent in Native Americans, Hispanics and possibly Asian Indians.
Definition or Criteria for diagnosis of DN
Presence of persistent proteinuria in sterile urine of diabetic patients with concomitant diabetic retinopathy and hypertension.

8. D.N.- Pathogenesis Familial - Genetic
Only 35-40% patients with IDDM develop DN.
There is an increased risk of DN in a patient with family member having DN.
Increased predisposition of Native Americans, Hispanic to DN.

9. D.N.- Pathogenesis Glycemic Control-in both expt & human
DN does not occur in euglycemic patients.
In early 80s some controversy but DCCT confirmed role of hyperglycemia in pathogenesis of DN.
Renal transplant with early DN showed structural recovery in euglycemic receipient. (Abouna)

10. Strict Glycemic Control Prevents Microalbuminuria in Type 1 Diabetes mellitus
From UpToDate v 6.2; Data from the DCCT Research Group, NEJM(1993) 329:977.

11. D.N.- Pathogenesis Glomerular Hyperfiltration Glomerular Hypertension
Glomerular Hypertrophy
GBM thickening
Mesangial Expansion

12. D.N.- Pathogenesis
Renal lesions mainly related to extracellular matrix accumulation
- Occurs in glomerular & tubular basement
membrane
- Principal cause of mesangial expansion
- Contributes to interstitium expansion

13. D.N.- Pathogenesis Extracellular matrix accumulation
- Imbalance between synthesis & degradation of
ECM components
- Linkage between glucose concentration & ECM
accumulation
- Transforming growth factor-Beta associated with
increased production of ECM molecules

14. D.N.- Pathogenesis Extracellular matrix accumulation
- TGF-B can down regulate synthesis of ECM
degrading enzymes & upregulate inhibitors of
these enzymes
- Angiotensin II can stimulate ECM synthesis
through TGF-B activity
- Hyperglycemia activates protein kinase C,
stimulating ECM production through cyclic AMP
Pathway

15. Diffuse and Nodular Glomerulosclerosis in Diabetic Nephropathy
From UpToDate
v 6.2
Courtesy
H. Rennke, M.D.

16. Diabetic Nephropathy

17. Advanced Diabetic Glomerulosclerosis
From: UpToDate
v 6.2
Courtesy
H. Rennke, M.D.

18. Diabetic Nephropathy

19. Diabetic Nephropathy Glomerular Basement Membrane Thickening
From: UpToDate
v 6.2
Courtesy
H. Rennke, M.D.

20. Natural Course of D.N. Stage 1: Renal hypertrophy - hyperfunction
Stage 2 : Presence of detectable glomerular lesion with normal albumin excretion rate & normal blood pressure
Stage 3 : Microalbuminuria
Stage 4 : Dipstick positive proteinuria
Stage 5 : End stage renal disease

21. Natural History of IDDM
Clinical type 1 diabetes
Functional changes*
Structural changes†
Microalbuminuria
Proteinuria
Rising blood pressure
Proteinuria
Rising serum creatinine levels
Diabetic nephropathy can be divided into 4 phases: microalbuminuria (urinary albumin excretion mg/24 h), macroalbuminuria or proteinuria (>300 mg/24 h), the nephrotic syndrome, and chronic renal failure (Grundy et al, 1999). Microalbuminuria is the first clinical sign of diabetic damage to the kidney and is a harbinger of progressive kidney damage. Microalbuminuria also reflects a higher risk for cardiovascular disease. Once microalbuminuria is present, it progresses over 5-10 years to macroalbuminuria in 22%-50% of patients (Mogensen, 1984; Cooper et al, 1988; Haneda et al, 1992; Ravid et al, 1992; John et al, 1994; Lebovitz et al, 1994). Macroalbuminuria denotes significant diabetic nephropathy and will be followed by a decline in glomerular filtration rate (GFR). Once a patient with type 2 diabetes develops macroalbuminuria, further decline in renal function appears to be inevitable; GFR declines at a rate of 4-12 mL/min/year (Pugh et al, 1993; Gall et al, 1993; Hasslacher et al, 1993). Some patients develop the nephrotic syndrome, which usually heralds progressive renal insufficiency and end-stage renal disease.
In diabetic nephropathy studies, where the time of onset of type 2 diabetes is known, these patients follow a time course similar to that seen in patients with type 1 diabetes. However, the date of onset of type 2 diabetes is often unknown and usually precedes the clinical diagnosis by several years (Grundy et al, 1999). By the time patients are diagnosed with type 2 diabetes, many have already developed hypertension, signs of nephropathy (including microalbuminuria or even macroalbuminuria) and cardiovascular disease (Mogensen et al, 1992; The Hypertension in Diabetes Study Group, 1993a; American Diabetes Association, 1998). Whereas patients with type 1 diabetes are usually normotensive until overt renal disease develops, hypertension commonly occurs in patients with type 2 diabetes before the onset of overt diabetic nephropathy, and about 40% of newly diagnosed patients with type 2 diabetes are already hypertensive (The Hypertension in Diabetes Study Group, 1993a). Both the onset of microalbuminuria and the progression of renal disease after the onset of macroalbuminuria are accelerated by hypertension (Epstein and Sowers, 1992).
The majority of patients with type 2 diabetes who have macroalbuminuria also have hypertension (Grundy et al, 1999). In these patients, control of hypertension slows the decline in GFR. The main goal of any treatment for patients with type 2 diabetic nephropathy should be to prevent the natural progression from microalbuminuria to macroalbuminuria to end-stage renal disease. Effective antihypertensive treatment is the best inhibitor of diabetic nephropathy (Ravid et al, 1993). Since reducing albuminuria delays progression of diabetic nephropathy, this parameter can be used as a benchmark for measuring the efficacy of therapeutic interventions (Rossing et al, 1994).
Note that the high risk of cardiovascular mortality in patients with type 2 diabetes, even early in their disease, may not allow for the development of nephropathy (Ismail et al, 1999).
End-stage renal disease
CV events 2 5 10 20 30
Onset of diabetes
Years
* Kidney size ­, GFR ­.
† GBM thickening ­, mesangial expansion ­

22. Natural History of NIDDM
Clinical type 2 diabetes
Functional changes*
Structural changes†
Rising blood pressure
Microalbuminuria
Proteinuria
Rising serum creatinine levels
Diabetic nephropathy can be divided into 4 phases: microalbuminuria (urinary albumin excretion mg/24 h), macroalbuminuria or proteinuria (>300 mg/24 h), the nephrotic syndrome, and chronic renal failure (Grundy et al, 1999). Microalbuminuria is the first clinical sign of diabetic damage to the kidney and is a harbinger of progressive kidney damage. Microalbuminuria also reflects a higher risk for cardiovascular disease. Once microalbuminuria is present, it progresses over 5-10 years to macroalbuminuria in 22%-50% of patients (Mogensen, 1984; Cooper et al, 1988; Haneda et al, 1992; Ravid et al, 1992; John et al, 1994; Lebovitz et al, 1994). Macroalbuminuria denotes significant diabetic nephropathy and will be followed by a decline in glomerular filtration rate (GFR). Once a patient with type 2 diabetes develops macroalbuminuria, further decline in renal function appears to be inevitable; GFR declines at a rate of 4-12 mL/min/year (Pugh et al, 1993; Gall et al, 1993; Hasslacher et al, 1993). Some patients develop the nephrotic syndrome, which usually heralds progressive renal insufficiency and end-stage renal disease.
In diabetic nephropathy studies, where the time of onset of type 2 diabetes is known, these patients follow a time course similar to that seen in patients with type 1 diabetes. However, the date of onset of type 2 diabetes is often unknown and usually precedes the clinical diagnosis by several years (Grundy et al, 1999). By the time patients are diagnosed with type 2 diabetes, many have already developed hypertension, signs of nephropathy (including microalbuminuria or even macroalbuminuria) and cardiovascular disease (Mogensen et al, 1992; The Hypertension in Diabetes Study Group, 1993a; American Diabetes Association, 1998). Whereas patients with type 1 diabetes are usually normotensive until overt renal disease develops, hypertension commonly occurs in patients with type 2 diabetes before the onset of overt diabetic nephropathy, and about 40% of newly diagnosed patients with type 2 diabetes are already hypertensive (The Hypertension in Diabetes Study Group, 1993a). Both the onset of microalbuminuria and the progression of renal disease after the onset of macroalbuminuria are accelerated by hypertension (Epstein and Sowers, 1992).
The majority of patients with type 2 diabetes who have macroalbuminuria also have hypertension (Grundy et al, 1999). In these patients, control of hypertension slows the decline in GFR. The main goal of any treatment for patients with type 2 diabetic nephropathy should be to prevent the natural progression from microalbuminuria to macroalbuminuria to end-stage renal disease. Effective antihypertensive treatment is the best inhibitor of diabetic nephropathy (Ravid et al, 1993). Since reducing albuminuria delays progression of diabetic nephropathy, this parameter can be used as a benchmark for measuring the efficacy of therapeutic interventions (Rossing et al, 1994).
Note that the high risk of cardiovascular mortality in patients with type 2 diabetes, even early in their disease, may not allow for the development of nephropathy (Ismail et al, 1999).
End-stage renal disease
Cardiovascular death
Onset of diabetes 2 5 10 20 30
Years
* Kidney size ­, GFR ­.
† GBM thickening ­, mesangial expansion ­

23. D.N.- Pathogenesis Hypertension - in both expt & human
Hypertension follows 8-10 years of hyperglycemia in IDDM patients but it is frequently present at the diagnosis of NIDDM.
Many experimental & human studies have shown HTN accelerating progressive renal injury in DN.

25. Effect of Angiotensin Blockade
Afferent arteriole
Efferent arteriole
¯ Glomerular pressure
¯ AER
(¯ GFR)
Glomerulus
Bowman’s Capsule
Proteinuria
Slide 21
Renal autoregulation
Angiotensin II
A II blockade:

26. Baseline creatinine >1.5 mg/dL
ACE-I Is More Renoprotective Than Conventional Therapy in Type 1 Diabetes
100 75 50 25
Baseline creatinine >1.5 mg/dL
% with doubling of baseline
creatinine
Placebo
n=202
P<.001
ACE-I Is More Renoprotective Than Conventional Therapy in Type 1 Diabetes
In this landmark trial by Lewis et al, the study design was a randomized, controlled trial in patients with type 1 diabetes who were treated with captopril (n=207) or placebo (n=202). Those assigned to captopril received 25 mg tid, and those assigned to the control group received placebo tid. Entry criteria included urinary protein excretion of >500 mg/day and serum creatinine <2.5 mg/dL. Blood-pressure goals were defined to achieve control during a median follow-up of three years. The recommended dietary protein intake was 1 g/kg of body weight per day. The primary end point was a doubling of the base-line serum creatinine concentration. As shown, the number of patients who experienced a doubling of baseline serum creatinine was reduced significantly (p<0.001) with captopril.
Reference:
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329(20):
Captopril
n=207 1 2 3 4
Years of follow-up
Lewis EJ, et al. N Engl J Med. 1993;329(20):

27. Brenner BM et al. N Engl J Med 345:861-869, 2001
RENAAL
Primary Composite End Point: Doubling of Serum Creatinine, ESRD or Death (Kaplan – Meier Curve)
Brenner BM et al. N Engl J Med 345: , 2001

28. RENAAL Brenner BM et al. N Engl J Med 345:861-869, 2001
Losartan could delay ESRD by years.
Brenner BM et al. N Engl J Med 345: , 2001

29. Irbesartan in patients with type 2 diabetes & microalbuminuria study
590 NIDDM patients with HTN and microalbuminuria with nearly normal GFR.
Randomly assigned to placebo, 150 mg or 300 mg of irbesartan for 2 years.
Primary outcome was time to the onset of diabetic nephropathy (urinary albumin excretion rate >200 mcg/min and at least 30% greater albuminuria)
14.9% patients on placebo group, 9.7% of irbesartan 150mg group and 5.2% of irbesartan 300 mg group reached the primary point.
(Parving et al, NEJM, 2001)

30. ARBs in NIDDM,HTN & microalbuminuria-Parving 2001

31. Lewis et al NEJM 2001

32. ACE-I + Verapamil: Additive Reduction of Proteinuria in Type 2 Diabetes at 1 Year
Trandolapril
(5.5 mg/d)
Verapamil
(315 mg/d)
Trandolapril (2.9 mg/d)
+ Verapamil (219 mg/d)
n=12
n=11
n=14
-27%
-33%
Percent reduction
ACE-I + Verapamil: Additive Reduction of Proteinuria in Type 2 Diabetes at 1 Year
The degree of proteinuria in patients with diabetes correlates strongly with both an increase in progression of nephropathy as well as cardiovascular events. Moreover, post hoc analyses of recent clinical trials support the concept that reductions of blood pressure and proteinuria correlate with a slowed progression of nephropathy. Both angiotensin converting enzyme (ACE) inhibitors and the non-dihydropyridine calcium antagonists (non-DHPCAs) reduce arterial pressure and proteinuria in those with diabetic nephropathy. The present randomized, open label, parallel group designed study tests the hypothesis that, at similar levels of blood pressure, the combination of an ACE inhibitor, trandolapril (T), with the non-DHPCA, verapamil (V), produces a greater reduction in proteinuria over either agent alone at one year. Thirty-seven participants, mean age /- 5.8 years, with nephropathy (baseline creatinine 1.4 +/- 0.3 mg/dl and proteinuria of /- 284 mg/dl) secondary to type 2 diabetes completed the study. Doses of drug were titrated in each group over 8 weeks to achieve a goal blood pressure of < 140/90 mmHg. All participants were counseled to ingest a sodium diet of < 120 mEq/day. Proteinuria reduction from baseline was significantly greater in the T+V group compared to either T alone (-33 +/- 8%, T vs -62 +/- 10%, T+V; P < 0.001) or V alone (-27 +/- 8%, V vs /- 10%, T+V; P < 0.001). No significant differences in either glomerular filtration rate, arterial pressure, fasting blood glucose or urinary sodium excretion were noted at one year. The mean daily dose of the individual components of T+V (2.9 +/- 0.8 mg, T/219 +/ mg V) was significantly lower than the dose of either T alone 5.5 +/- 1.1 mg/day (P < 0.01) or V alone / mg, given in two divided doses (P < 0.01). These data support the concept that the combination of an ACE inhibitor with a non-DHPCA reduce proteinuria to a greater extent than either agent alone. This added anti-proteinuric effect occurs at lower doses of each drug, and is independent of further reductions in arterial pressure. These findings could have ramifications for slowing renal disease progression in patients with nephropathy from type 2 diabetes.
Reference:
Bakris GL, Weir MR, DeQuattro V, McMahon FG. Effects of an ACE inhibitor/calcium antagonist combination on proteinuria in diabetic nephropathy. Kidney Int. 1998; 54(4):
-62% *
*p <0.001 combination vs either monotherapy
Bakris GL, et al. Kidney Int. 1998;54:
Reprinted by permission, Blackwell Science, Inc.

33. D.N.-Management ACEI or AII RB- in both expt & human
Reduce glomerular hypertension
Reduce proteinuria independent of hemodynamic effects
Reduce glomerular hypertrophy
well tolerated apart from hyperkalemia & worsening of anemia in severe CRF
Cautious use in presence of severe renovascular disease

34. DN: ADA Position Statement
Screening:
Perform an annual test for the presence of microalbuminuria in
type 1 diabetic patients who have had diabetes > 5 years and
all type 2 diabetics patients starting at diagnosis.
Treatment:
In the treatment of albuminuria/nephropathy both ACE inhibitors and ARBs can be used:
In hypertensive and nonhypertensive type 1 diabetic patients with microalbuminuria or clinical albuminuria, ACE inhibitors are the initial agents of choice
In hypertensive type 2 diabetic patients with microalbuminuria or clinical albuminuria, ARBs are the initial agents of choice.
If one class is not tolerated, the other should be substituted
American Diabetes Association: Position Statement Diabetes Care 25:S85-S89, 2002

35. Better blood pressure control reduces…
UK Prospective Diabetes Study (UKPDS) Major Results: Powerful Risk Reductions
Better blood pressure control reduces…
Strokes by > one third
Serious deterioration of vision by > one third
Death related to diabetes by one third
Better glucose control reduces…
Early kidney damage by one third
Major diabetic eye disease by one fourth
UK Prospective Diabetes Study (UKPDS) Major Results: Powerful Risk Reductions
The United Kingdom Prospective Diabetes Study (UKPDS) included an evaluation of baseline risk factors for macrovascular and microvascular complications in patients with type 2 diabetes mellitus. A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are: increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycemia, and smoking. The control of elevated blood pressure and elevated glucose can reduce, by up to a third, the risk for complications from diabetes. The specific end-organ benefits of blood pressure control and glucose control are shown on this slide.
References:
Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ 1998;316(7134):
Turner RC, et al. BMJ. 1998;317:

36. UKPDS: Relationship Between BP Control And Diabetes-Related Deaths
17% decrease per 10 mmHg decrement in BP
p<0.0001 . 5 1 2 3 4 6 7
Hazard ratio
UKPDS: Relationship Between BP Control And Diabetes-Related Deaths
In patients with type 2 diabetes, the risk of diabetic complications is strongly associated with raised blood pressure. UKPDS determined the relationship over time between systolic blood pressure and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. This was a prospective observational study in 23 hospital-based clinics in England, Scotland, and Northern Ireland. There were 4801 white, Asian Indian, and Afro-Caribbean UKPDS patients included in analyses of incidence and 3642 were included in analyses of relative risk. The primary predefined aggregate clinical outcome was any complications or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes were myocardial infarction, stroke, lower extremity amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photocoagulation). Risk reduction associated with a 10 mmHg decrease in updated mean systolic blood pressure adjusted for specific confounders. The incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mmHg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 17% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure <120 mmHg.
Reference:
Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, Wright AD, Turner RC, Holman RR. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000; 321(7258):  
Mean systolic blood pressure (mmHg)
Adler AI, et al. BMJ. 2000;321:
Reprinted by permission, BMJ Publishing Group.

37. Diabetes: Tight Glucose vs Tight BP Control and CV Outcomes in UKPDS
Stroke
Any Diabetic
Endpoint DM
Deaths
Microvascular
Complications 5%
10%
-10
12%
-20
24%
% Reduction In Relative Risk *
-30
32%
32%
Diabetes: Tight Glucose vs Tight BP Control and CV Outcomes in UKPDS
A comparison of tight glucose control, HbA1c=7% (achieved was 8.2%) vs tight blood pressure control <150/85 mmHg (achieved 144/82 mmHg) revealed that blood pressure reduction contributed to a greater extent to the relative reduction of cardiovascular events.
References:
Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):
Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160): *
37%
*P <0.05 compared to tight glucose control *
-40
44%
Tight Glucose Control
(Goal <6.0 mmol/l or 108 mg/dL)
Tight BP Control
(Average 144/82 mmHg) *
-50
Bakris GL, et al. Am J Kidney Dis. 2000;36(3):
Reprinted by permission, Harcourt Inc.

38. Blood pressure goal: 130/80 mmHg
National Kidney Foundation Recommendations on Treatment of HTN and Diabetes
Blood pressure goal: 130/80 mmHg
Target blood pressure: 125/75 for patients with >1 gram/day proteinuria
Blood pressure lowering medications should reduce both blood pressure + proteinuria
Therapies that reduce both blood pressure and proteinuria have been known to reduce renal disease progression and incidence of ischemic heart disease
National Kidney Foundation Recommendations on Treatment of HTN and Diabetes
The blood pressure treatment goal for diabetics with hypertension proposed by the National Kidney Foundation Hypertension and Diabetes Executive Committee consensus report is 130/80 mmHg. If the patient has proteinuria > 1gm/day, goal blood pressure should be reduced further to 125/75 mmHg. The goal of treatment is not only to reduce blood pressure to goal, but to reduce or eliminate proteinuria to the extent possible. Certain medications, such as the ACE inhibitors and the angiotensin receptor blockers, appear to be more effective in achieving this combined end point than other anti-hypertensive agents. A reduction in both blood pressure and proteinuria has been associated with a reduction in the incidence of ischemic heart disease or in its progression in diabetic patients with pre-treatment cardiac ischemic conditions or impaired renal function.
Reference:
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):
Bakris GL, et al. Am J Kidney Dis. 2000;36(3):

39. Cholesterol Lowering Therapy and Diabetic Nephropathy
Randomized single-blinded study
34 NIDDM patients
Lovastatin or Placebo
Followed for 2 years
GFR
ml/min
Months
Lam, etal. Diabetologia (1995) 38:

40. Management of ESRD due to DN
Early planning of Vascular Access
Both HD & PD could be appropriate modalities.
Early initiation of Dialysis at GFR mls/min.
Renal Transplantation
CHD very common even in absence of symptoms.
Coronary Angiogram in diabetics under 40 years age.
Combined Renal & Pancreatic Transplantation for IDDM.

41. Comparison of Patient Survival on Hemodialysis
and CAPD by Cause of Renal Failure
From UpToDate v 6.2; Data from Nelson, et al JASN(1992)3:1147.

42. Simultaneous Pancreas-Kidney Transplantation
Patient and Graft Survival
From:
UpToDate
v 6.2

43. Screening for microalbuminuria in diabetes

44. Hypercholesterolemia LDL < 100 mg/dL Hyperglycemia
Treatment Objectives to Prevent Macrovascular Disease in Diabetic Patients
Hypertension
BP < 130/80 mmHg
Hypercholesterolemia
LDL < 100 mg/dL
Hyperglycemia
Hgb A1C < 7.0 %
Treatment Objectives to Prevent Macrovascular Disease in Diabetic Patients
The results of clinical trials in diabetic patients at increased cardiovascular and renal risk suggest that aggressive control of hypertension may be the most cost-effective in reducing risk, followed, in rank order, by aggressive management of dyslipidemia and then by tight blood glucose control. The recommended goals for reduction of blood pressure (BP) are to values <130/80 mmHg, for reduction of LDL cholesterol to <100 mg/dL, and for reduction of hemoglobin A1c to <7.0%.
Reference:
American Diabetes Association Clinical Practice Recommendations Diabetes Care. 2001;24(suppl1):S1-S133.
American Diabetes Association Clinical Practice Recommendations. Diabetes Care. 2001;24(suppl1):S1-S133.

45. Management of HTN and Chronic Renal Disease (CRD) in Diabetics
Reduce BP to <130/80 mmHg
Use multiple antihypertensive drugs (ACEI, ARB, diuretic, CCB, beta-blocker)
Maximal reduction of proteinuria
Treat hyperlipidemia (LDL <100 mg/dL)
Control Hgb A1C to <7%
Low salt diet (<2 gm NaCl/day)
Stop cigarette smoking
Management of HTN and Chronic Renal Disease (CRD) in Diabetics
The management of hypertension and chronic renal disease in diabetics should be even more aggressive than in the non-diabetic. The goal of anti-hypertensive therapy should be blood pressure values <130/80 mmHg, except in those diabetics who have > 1gm/day of proteinuria. In the latter patients, the goal blood pressure should be <125/75 mmHg. Multiple anti-hypertensive drugs will usually be required to achieve these blood pressure goals. Drugs or drug combinations that are most effective in reducing or abolishing proteinuria should be used, and the doses modified based on frequent determination of urine protein, until the desired effect is achieved. Effective risk factor management of diabetics also includes control of hyperlipidemia and hyperglycemia. Modest dietary protein restriction is recommended for the hypertensive diabetic whose creatinine clearance is already diminished. Sodium restriction is indicated in patients with CRD and impaired ability to excrete sodium. Smoking cessation is key to successful cardiovascular risk reduction.

46. Thanks for your attention