Presentation is loading. Please wait.

Presentation is loading. Please wait.

Diabetic Nephropathy in T2DM: Blood Pressure and Cholesterol Targets

Similar presentations


Presentation on theme: "Diabetic Nephropathy in T2DM: Blood Pressure and Cholesterol Targets"— Presentation transcript:

1 Diabetic Nephropathy in T2DM: Blood Pressure and Cholesterol Targets
Nemanja Stojanović Consultant Endocrinologist Queen’s Hospital, Romford

2 We will talk about Kidney in Diabetes
Drug related renal injury in T2DM Preventing DM Nephropathy Cholesterol/ BP/ Glucose Treatment Guidelines/ Conclusion

3 Nephropathy 35-50% with Type 1 after 20 years of disease
10- ? 20% Type 2 patients on diagnosis

4 Nephropathy: aetiology
HbA1c >7–8% Genetic factors Hypertension Inflammation Altered vascular permeability Hyperlipidaemia Excessive protein intake

5 Determinants of Glomerular Proteinuria
Mean transcapillary hydraulic-pressure difference Glomerular surface area Size selectivity of the glomerular filter Charge selectivity

6 Microalbuminuria Normoalbuminuria <30 mg/day
Microalbuminuria 30–300 mg/day Clinical or macroalbuminuria >300 mg/day- POINT OF NO RETURN ACR

7 Nephropathy: Patient Should Know…
Optimal glycaemic control will prevent it or delay it Annual urine test: only way to detect it Importance of BP monitoring Hypertension: predisposes and aggravates nephropathy

8 Microalbuminuria: Type 2 DM
10% have it at diagnosis 80% CVS mortality over 10 years Associated with insulin resistance sy 2 positive samples required for the diagnosis

9 STENO-2 Study 160 patients with T2DM and microalbuminuria
80 treated according to the national guidelines + 80 active treatment Active group reviewed 3 monthly Duration: 7.8 years NEJM 2003; 348:

10 STENO-2 Study Intensive glycaemic control A1c < 7.5 or 6.5%
Systolic Bp < 140 or 130 mmHg Diastolic BP < 85 or 80 mm Hg Cholesterol < 4.9 or 4.6 mmol/l Triglycerides < 1.7mol/l Most active treatment patients were on Aspirin NEJM 2003; 348:

11 STENO-2 Endpoints Composite death from CVS causes CVG PTCA
Nonfatal CVA Amputation Vascular surgery to correct ischaemia Microvascular NEJM 2003; 348:

12 STENO-2 After the end of the study Prospective follow up for 5.5 years
Both groups now treated to the national targets

13 Preventing Microalbuminuria and Progression of Diabetic Nephropathy: Antihypertensives

14 Preventing Microalbuminuria in T2DM: BENEDICT Study
1204 Hypertensive Subjects with T2DM No microalbuminuria Target BP 120/80 HbA1c ~ 5.8± 1.5% Duration of Diabetes< 25 years NEJM 351: ; 2004

15 Preventing Microalbuminuria in T2DM
Trandolapril Trandolapril + Verapamil Verapamil Placebo N= 301 300 303 Microalb-uminuria 6% 5.7% 11.9% 10% BP over baselinemmHg 151/87 150/87 152/87 NEJM 351: ; 2004

16 Irbesartan in T2DM Nephropathy
1715 pts- duration 2.6 years Irbesartan 300mg OD vs Amlodipine OD vs Placebo Proteinuria 900mg/day Cr ♀ umol/l ♂ umol/l Target BP 135/85 mmHg Primary composite outcome: ESRF, doubling of Cr & Death: any cause NEJM 2001; 345:

17 Irbesartan in T2DM Nephropathy
Amlodipine Placebo N 579 567 569 BP achieved 140/ 77 mmHg 141/ 77 mmHg 144/ 82 mmHg Renal Outcome Irbesartan group 23% better than Amlodipine and 20% than Placebo CVS mortality: no difference NEJM 2001; 345:

18 Losartan and Diabetic Nephropathy
Secondary outcomes Composite of morbidity and mortality from cardiovascular causes (p=NS) Proteinuria Losartan: 35% reduction Progression of renal disease Losartan: 18% reduction NEJM :

19 Irbesartan In patients with microalbuminuria
Renoprotective, prevents albuminuria in hypertensive patients with T2DM Higher dose was more effective A higher proportion of patients restored normoalbuminuria Irbesartan 300mg OD group than placebo 34% vs 21% Parving H et al. N Engl J Med 2001;345:

20 Telmisartan vs Enalapril
Patients with early diabetic nephropathy 250 subject over 5 years Similar decrements in GFR in both groups: ml/min/1.73m2 of body surface area Cr, AER no difference N Engl J Med 2004; 351:

21 Drugs: Frequent Offenders
Iodine based contrast Metformin & Contrast NSAIDS & COX-2 Inhibitors ACE ARBs Aminoglycoside antibiotics Amphotericin B Immunosuppressants

22 Lipids ± Diabetes

23 At least One Complication
Hypertension Retinopathy/ Maculopathy/ Previous laser Smoking Micro or macroalbuminuria LDL < 4.14 mmol/l Triglycerides< 6.78mmol/l The Lancet 2004; 364:

24 CARDS 1% 6% 30% 63% The Lancet 2004; 364:

25 Primary Endpoints Acute coronary heart disease event (incl. MI, silent MI, unstable angina, death, CPR) Coronary revascularisation procedures Stroke The Lancet 2004; 364:

26 Primary Endpoints: Results
No difference between the sexes or risk factor subgroups Acute coronary heart disease event % Coronary revascularisation procedures % Stroke % The Lancet 2004; 364:

27 CARDS 743 patients 26% reduction in major cardiovascular events
LDL < 2.6mmol subgroup 743 patients 26% reduction in major cardiovascular events The Lancet 2004; 364:

28 REVERSAL Trial Endovascular USS
Pravastatin 40mg vs Atorvastatin 80mg OD Baseline LDL: 3.89mmol/l End of Study LDL: Pravastatin 2.85mmol/l Atorvastatin 2.05mmol/l After 18/12 atheroma progressed in pravastatin group but not in Atorvastatin group JAMA. 2004; 291:

29 Drugs on Offer Simvastatin Atorvastatin Pravastatin Rosuvastatin
Ezetamibe Niacin Fibrates Omacor Diet

30 Equivalent Doses Atorvastatin+ Simvastatin Pravastatin Rosuvastatin
LDL Reduction % Atorvastatin+ 10 39 Simvastatin 20-40 35-41 Pravastatin 40 34 Rosuvastatin 5-10 39-45 Fluvastatin 40-80 25-35 Ezetamibe 16-18 (12-21c) + max dose decreases the LDL by additional 20%

31 Metabolism Atorvastatin Simvastatin Pravastatin Rosuvastatin
cytochrome P 450 3A4 Simvastatin Pravastatin 70% faeces, 20 % urine; 7 different sets of enzymes Rosuvastatin 90% unchanged in faeces Fluvastatin 2C9 isozyme systems (75%) Ezetamibe 70 % faeces unchanged; conjugation with glucuronide

32 Effect of reduction of LDL by 1mmol/l by any means on coronary death and non-fatal MI: meta-analysis of 58 trials Law MR BMJ 2003, 326:

33 Ahead of the Press

34 ADVANCE 11140 patients: 5 years
Intensive glycaemic control (A1c 6.5%) vs Conventional (A1c 7.3%) Intensive group: gliclazide MR 30 to 120 mg daily and other hypoglycamic agents including insulin N Engl J Med 2008; /NEJMoa

35 ADVANCE Primary Endpoints
Composite of macro and microvascular events considered jointly and separately Macro: CVD death, non fatal CVA & MI Micro:new or worsening nephropathy ; doubling of the serum creatinine; the need for dialysis; death due to renal causes; worsening of retinopathy N Engl J Med 2008; /NEJMoa

36 ADVANCE Intensive Rx Conventional Rx n 5571 5569 6.5% 7.3%
Study End A1c 6.5% 7.3% Gliclazide MR 90% (30-120mg OD) NA Insulin 40.5% 24.1% Weight > 0.7kg Prim outcome 18.1% 20% N Engl J Med 2008; /NEJMoa

37 ADVANCE Conclusion The main contributor to the 10% relative reduction in the primary outcome found with intensive control as compared with standard control was a 21% relative reduction in the risk of new or worsening nephropathy More modest but significant reduction in microalbuminura N Engl J Med 2008; /NEJMoa

38 ACCORD Trial 10,251 patients Intensive glycaemic control and CVS outcomes Primary outcomes : CVD death, Non fatal CVA & MI Intensive Treatment: HbA1c< 6% Conventional Treatment HbA1c 7-7.9 Death rates begin to separate after 1 year….. N Engl J Med 2008; /NEJMoa

39 ACCORD Intensive (%) Conventional(%) 5128 5123 538 (10.5) 179 (3.5)
Hypoglycaemia 538 (10.5) 179 (3.5) Weight gain> 10kg 1399 (27.8) 713 (14.1) CVD Death 135 (2.6) 94 (1.8) Non fatal MI 186 (3.6) 235 (4.6) Non fatal CVA 67 (1.3) 61 (1.2) Any Death 257 (5) 203 (4) N Engl J Med 2008; /NEJMoa

40 NICE BP < 130/80 ACE/ ARB Cholesterol<4mmol/l LDL< 2mmol/l
Aspirin

41 Instead of Conclusion If I had T2DM and microalbuminuria:
BP 129 (114)/ 79 mmHg LDL < 2mmol/l ACE or ARB Aspirin

42


Download ppt "Diabetic Nephropathy in T2DM: Blood Pressure and Cholesterol Targets"

Similar presentations


Ads by Google