1. Dr M Sivalingam Renal Unit, Lister Hospital, Stevenage

2.  Diabetes is the leading cause of ESRF  >40% new patients starting dialysis in USA  ~30% of patients in Western Europe

3. Incident ESRD patients USRDS - 2009

5. Months on Dialysis 908478726660544842363024181260 Cumulative Survival 1.0.9.8.7.6.5.4.3.2.1 0.0 P = 0.02 n = 59 Non-diabetics Diabetics n = 231 Prognosis on Renal Replacement Therapy

6.  Incidence decreasing in Type 1 Diabetics

7. Copyright restrictions may apply. Finne, P. et al. JAMA 2005;294:1782-1787. Incidence Rate of End-stage Renal Disease According to Time Period of Diagnosis of Type 1 Diabetes Finnish Diabetes Register >20000 pts

8. 1.NICE Management of type 2 diabetes: NICE 2008 2.NICE Management of CKD: NICE 2008

9. NICE Type 2 Diabetes Guidance NICE Management of type 2 diabetes: NICE 2008 First-pass urine specimen Once annually UACR Request specimen if UTI prevents analysis Measure serum creatinine (SeCr) and calculate eGFR (MDRD) annually at the time of ACR estimation Repeat the test if abnormal ACR Result of MAU confirmed if further abnormal specimen

10. StageDescriptionGFR 1 Kidney damage, N or  GFR ≥90 2 Kidney damage, mild  GFR 60-89 3A 3B Moderate  GFR 45-59 30-44 4 Severe  GFR 15-29 5Kidney failure<15 (or dialysis) Stages of CKD

11.  Glycaemic control  Blood pressure management  MAU/proteinuria  Lipid management  Lifestyle management  Antiplatelet therapy NICE Type 2 Diabetes Guidance

12. CKD 2CKD 2+CKD 3CKD 4 N14202174111278777 Male43.856.537.835.9 Age (yrs)61.4 ±14.160.8 ±14.971.6 ±11.973.6±13.6 Death (%)10.219.524.345.7 RRT (%)0.071.1 1.319.9 Keith et al Arch Intern Med 2004;164:659-663 Death far more common than RRT at all stages

13.  ACE or ARB in normal doses  Supra-maximal doses of ARB  Combination therapy  Direct Renin Inhibitors  Aldosterone antagonists

14.  269 patients  ~ 50% diabetic  1gm proteinuria  Median SCr 150 Burgess et al, JASN 20: 893–900, 2009 Withdrawn due to hyperkalaemia in about 4%

15.  What about combination therapy?

17.  Patients at low risk of progressive CKD  Mean eGFR 73.6 mls / min  Mean ACR 0.81 mg/mmol  No of patients needing chronic dialysis very low in all arms  Primary renal outcome driven by death (80%)

18.  Type 2 Diabetes with Nephropathy  Olmesartan or Placebo with standard therapy  577 patients, 72% received ACE  Follow up 3 years  Doubling of SCr, ESRD or death  Preliminary results - WCN

20. 599 patients Aliskiren or placebo to Losartan ACR decreased by 20% Parving et al

21.  Reduces proteinuria when used alone  Additive effect of Spironolactone  Blood pressure effect as well as ?anti inflammatory effect

22. 59 patients with DM Already on ACE or ARB Randomised to Spiro or placebo 5 – high K ACR decreased by 40% van den Meiracker et al

23.  Diabetics receiving 80 mg/d lisinopril, and had a urine albumin-creatinine ratio (ACR) of 300 to placebo, losartan100 mg/d, or Spironolactone 25 mg/d for 48 wks  Greatest antiproteinuric effect with Spironolactone  Similar degrees of BP lowering in all groups  Significant incidence of asymptomatic hyperkalaemia (6.0) in about 50% Mehdi et al, JASN 2009

24. 1. Progressive stage 4 and 5 CKD (with or without diabetes) 2. Heavy proteinuria (ACR ≥70 mg/mmol, approximately equivalent to PCR ≥100 mg/mmol, or urinary protein excretion ≥1g/24 hours) unless known to be due to diabetes and already appropriately treated 3. Proteinuria (ACR ≥30 mg/mmol, approximately equivalent to PCR ≥50 mg/mmol, or urinary protein excretion ≥0.5 g/24 hours) together with haematuria 4. Rapidly declining eGFR (>5 ml/min/1.73 m 2 in one year, or >10 ml/min/1.73 m 2 within 5 years) 5. Hypertension that remains poorly controlled despite the use of at least 4 antihypertensive drugs at therapeutic doses people with, or suspected of having rare or genetic causes of CKD 6. Suspected renal artery stenosis If in doubt, please refer or write to us rather than Choose and Book

25. Thank you