diabetic nephropathy.ppt

7/27/2019 DIABETIC NEPHROPATHY.ppt

1/14

DIABETIC NEPHROPATHY

Luthfan Budi PurnomoDivision of Endocrinology

Internal Medicine DepartmentSchool of Medicne Gadjah Mada UniversityDr Sardjito Hospital Jogjakarta


2/14

INTRODUCTION

Prevalence of diabetes increases: 14.7% in urban areaand 7.2% in rural area (PERKENI, 2006)

Diabetes has become the number one cause of end-

stage renal disease (ESRD) Early diagnosis of diabetes and early intervention are

critical in preventing the normal progression to renalfailure


3/14

Definition of diabetic nephropathy

Diabetic nephropathy (DN) is defined by eithermacroalbuminria (a urinary albumin excretion ofgreater than 300 mg/day or urinary albumin:creatinine ratio/ACR >30 mg/mmol) or by abnormalrenal function and with existing diabetic retinopathy

Microalbuminuria (earliest sign of DN or incipientDN) is defined by a urinary albumin excretion of 30-300 mg/day or ACR >2,5 mg/mmol in men and >3,5 in

women

(DeFronzo, 2005; Augustine and Vidt, 2003)


4/14

Flowchart for diagnosis of diabetic nephropathy

Annual dipstickUrinalysis for protein

Positive Negative

Previously positiveon 2 occasions overprevious 12 months

Test for microalbuminria

YES NO

Positive

YES NO

Retinopathy +

YES

Clinical nephropathy

Retest over next12 months

Positive

YES NO

ACR >2,5 mg/mmolor >3,5 mg/mmol

YES NO

Confirm with2 samples if2/3 positive

Microalbuminuria

Retest over next6 months

Jones et. al., 2006


5/14

Prevalence of type 1 and type 2 diabetes in UnitedStates and progression of microalbuminuria anddiabeticnephropathy

Type 1 Type 2

Prevalence of disease

Prevalence of microalbuinuria

at 15 yearsPrevalence of macroalbuminuriaat 15 years

Progression to end-stage renaldisease 10 years after onset of

macroalbuminuria

0.85-1.7 million

21%

21%

50%

15,3-16,2 million

28%

14%

10%

(Augustine and Vidt, 2003)


6/14

Pathogenesis of diabetic nephropathy

METABOLIC

Vascular

METABOLIC HEMODYNAMIC

CytokinesTGF- VEGF

Glucose Flow/Pressure

PKC-IIVasoactive hormones

(A-II, Endothelin)

AGEs

Extra-cellular matrix

Cross-linking

Vascularpermeability

Extra-cellularmatrix

Extra-cellular matrixaccumulation

Proteinuria


7/14

Natural course of diabetic nephropathy

-3 0 3 Time (years) 15 20 25

-3 0 3 10 15 20 25

120 150 150 GFR (mL/mnt) 120 60 2.0 >10

15 10 10 Serum urea nitrogen (mg/dL) 15 >30 >100

Microalbuminuria

Prior toonset ofdiabetes

Onset ofdiabetes

Onset ofdiabeticglomerulosclerosis

Onsetof

proteiuria

Onsetofazotemia

ESRD

(DeFronzo, 2005)


8/14

Features that suggest non-diabetic kidneydisease

Rapid deterioration in renal function

Sudden development of nephrotic syndrome

Heavy hematuria/red cell casts

Absence of diabetic retinopathy

Short duration of type 1 diabetes

Clinical or laboratory evidence of non-diabeticsystemic disease

Blood pressure higher than expected for degree ofproteinuria

Jones et. al., 2004


9/14

Risk factors of diabetic nephropathy

Blood glucose level

Blood pressure

Male sex

Duration of diabetes

Total cholesterol level


10/14

Treatment of diabetic nephropathy

Blood glucose control

Blood pressure control

Protein restriction

Cholesterol lowering

(Steele, 2001)


11/14

The role of glycemic control

DCCT: A1c 7.2% vs 9.2% 39% risk reduction in thedevelopment of microalbuminuria and 54% riskreduction in the development of macroalbuminuria

UKPDS: A1c 7% vs 7.9% 0.76 relative risk (24%risk reduction) for the development of micro-albuminuria (Jones et. al., 2004; Augustine and Vidt,2003)

Good glycemic control (A1c


12/14

The role of blood pressure control Normotensive, normoalbuminuric T1D patients:

There is no evidence that antihypertensive treatment preventsor delays the onset of microalbuminuria (Jones et al., 2004)

T2D patients:Blood pressure control reduces the development ofmicroalbuminuria (Jones et al., 2004)

ACEIs reduce 75% UAER after 1 year treatment in T1Dpatients Irbesartan 300 mg in 2 years treatment reduces 32% the

development of clinical nephropathy (in T2D patients) Target of blood pressure 130/80 mmHg. Once renal function

starts to decline and proteinuria reaches 1 g/d T 125/75mmHg Each 10 mmHg reduction improves the relative decline in renal

function by 0.18 ml/min/mo (Steele, 2001)


13/14

Blood pressure goal and recommended agents

Goal bloodpressure Blood pressure agents ofchoice

T1DM

T2DM

DM with macroalb.

DM with CHF

DM with CAD


14/14

The role of protein restriction Protein restriction (0.8-1.0 g/kg body weight/d)

reduces the decline in glomerular filtration rate(relative risk of the decline in GFR: 0.56) (Steele,2001)

Dietary protein intake amounting to >20% of total

energy was linked to the presence ofmicroalbuminuria (Jones et al., 2004)

Protein and phosphate restricted diet reduced adecline of GFR of only 0,26 ml/min/mo (Evants and

Capell, 2000) RDA protein of 0.8 g/kg body weight/d or 10% of

total calories (Evants and Capell, 2000)

diabetic nephropathy.ppt

Documents