Dr M SivalingamRenal Unit, Lister Hospital, Stevenage

Diabetes is the leading cause of ESRF

>40% new patients starting dialysis in USA

~30% of patients in Western Europe

Incident ESRD patients USRDS - 2009

USRDS - 2009

Months on DialysisMonths on Dialysis

909084847878727266666060545448484242363630302424181812126600

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1.01.0

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P = 0.02P = 0.02n = 59n = 59

Non-diabeticsNon-diabetics

DiabeticsDiabetics

n = 231n = 231

Prognosis on Renal Replacement Prognosis on Renal Replacement TherapyTherapy

Incidence decreasing in Type 1 Diabetics

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 DiabetesFinnish Diabetes Register >20000 pts

1. NICE Management of type 2 diabetes: NICE 20082. NICE Management of CKD: NICE 2008

NICE Type 2 Diabetes Guidance

NICE Management of type 2 diabetes: NICE 2008

First-pass urine specimenOnce annuallyUACRRequest 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

Stage Description GFR

1 Kidney damage, N or GFR ≥90

2 Kidney damage, mild GFR 60-89

3A

3B

Moderate GFR

Moderate GFR

45-59

30-44

4 Severe GFR 15-29

5 Kidney failure <15 (or dialysis)

Stages of CKD

Glycaemic control Blood pressure management MAU/proteinuria Lipid management Lifestyle management Antiplatelet therapy

NICE Type 2 Diabetes Guidance

CKD 2 CKD 2+ CKD 3 CKD 4

N 14202 1741 11278 777

Male 43.8 56.5 37.8 35.9

Age (yrs) 61.4 ±14.1 60.8 ±14.9 71.6 ±11.9 73.6±13.6

Death (%) 10.2 19.5 24.3 45.7

RRT (%) 0.07 1.1 1.3 19.9

Keith et al Arch Intern Med 2004;164:659-663

Death far more common than RRT at all stages

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

269 patients

~ 50% diabetic

1gm proteinuria

Median SCr 150

Burgess et al, JASN 20: 893–900, 2009

Withdrawn due to hyperkalaemia in about 4%

What about combination therapy?

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%)

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

599 patients

Aliskiren or placebo to Losartan

ACR decreased by 20%

Parving et al

Reduces proteinuria when used alone Additive effect of Spironolactone Blood pressure effect as well as ?anti

inflammatory effect

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

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

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 m2 in one year, or >10 ml/min/1.73 m2 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

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