Diabetic Nephropathy Fariz

DIABETIC NEPHROPATHY
Ahmad Fariz Malvi Zamzam Zein

SMF ILMU PENYAKIT DALAM
RSUD WALED
DEFINITION AND EPIDEMIOLOGY
• Diabetic nephropathy : presence of proteinuria > 0.5
g/24 h.1
• Persistent microalbuminuria (30-299 mg/24 h) ~ the
earliest stage in T1DM, a marker for development of
nephropathy in T2DM, and a marker of increased CVD
risk.2
• It occurs in 20-40 % of pts with diabetes and is the single
leading cause of ESRD.2
1. Gross JL, et al. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care, 28:
176-88, 2005
2. American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care.
36(S1):S11-66, 2013
• T1DM :
– Incidence of microalbuminuria : 12.6 % over 7.3 years
(EURODIAB Prospective Complications Study Group) and ~
33 % in an 18-year follow-up study in Denmark
– Proteinuria occurs in 15-40 % (peak incidence 15-20 years
of diabetes)
• T2DM :
– Incidence of microalbuminuria : 2.0 % per year
– Prevalence is highly variable (5-20 %)
Gross JL, et al. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care, 28: 176-
88, 2005
• >> African Americans, Asians and native
Americans than Caucasians.
88, 2005
PATOPHYSIOLOGY
Kanwar YS, et al. Diabetic nephropathy: mechanisms of renal disease progression. Experimental
Biology and Medicine. 2008, 233:4-11
PATOPHYSIOLOGY
Kanwar YS, et al. Diabetic nephropathy: mechanisms of renal disease progression. Experimental
Biology and Medicine. 2008, 233:4-11
Ritz E, Wolf G. Chapter 29 : pathogenesis, clinical manifestations, and natural history of diabetic
nephropathy. In : Floege J,et al. Comprehensive clinical nephrology. 4th ed. Missouri. 2010
Nephron Changes in Diabetes and
After Administration of ACE-I or ARB
Nephron Changes in Diabetes
Pathological Changes Characteristics of
Diabetic Glomerulosclerosis
William ME, et al. Diabetic kidney disease: current challenges. In : Himmelfarb J, et al. Chronic
kidney disease, dialysis and transplantation. 3th ed. Philadelphia. 2010
Crosstalk between endothelial cells
and podocytes
Time Course of Development of
Diabetic Nephropathy
Longo DL, et al. Harrison’s Principles of Internal Medicine. 18th edition.

SCREENING
• Perform an annual test to assess urine
albumin excretion in T1DM patients with
diabetes duration of > 5 years and in all T2DM
patients starting at diagnosis.(B)
• Measure serum creatinine at least annually in
all adults with diabetes regardless of the
degree of urine albumin excretion. (E)
American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care.

36(S1):S11-66, 2013
DIAGNOSIS
• Measurement of urinary albumin
• Measurement of serum creatinine
concentration and estimation of GFR
• Measurement of blood pressure
• Ophthalmologic examination
Measurement of urinary albumin
• Microalbuminuria : excretion of 30-300 mg/24
h albumin in at least 2 of three consecutive
non ketotic sterile urine samples.
Measurement of urinary albumin
• Searching for microalbuminuria in the course
of diabetes  predicts a high renal and CV risk
 allows targeted intervention.
DIABETIC NEPHROPATHY STAGES
Stages Albuminuria cutoff Clinical characteristics
values
Microalbuminuria 20 – 199 μg/min Abnormal nocturnal decrease of blood
pressure and increased blood pressure level
30 – 299 mg/24 h Increased triglycerides, total and LDL
cholesterol, and saturated fatty acid
30 – 299 mg/g Increased frequency of metabolic syndrome
components, endthelial dysfunction,
association with diabetic retinopathy,
amputation and cardiovascular mortality
Macroalbuminuria > 200 μg/min Hypertension
> 300 mg/24 h Increased triglycerides and total/LDL
> 300 mg/g Asymptomatic myocardial ischemia,
progressive GFR decline.
88, 2005
Measurement of blood pressure
• A nighttime increase in BP is indepedently
associated with a 20-fold higher mortality and
higher risk of renal failure.
• Occasional measurement of ambulatory BP 
useful to assess the efficacy of AH treatment.
STAGES OF CKD
Stage Description GFR (mL/min/1.73

m2 BSA)
1 Kidney damage with normal or increased > 90
GFR
2 Kidney damage with mildly decreased GFR 60 – 89
3 Moderately decreased GFR 30 – 59
4 Severely decreased GFR 15 – 29
5 Kidney failure < 15 or dialysis

36(S1):S11-66, 2013
Ophtalmologic examination
• Patients with microalbumnuria and diabetic
retinopathy  fastest GFR decline.
• Albuminuria and diabetic retinopathy  risk
factors of renal prognosis in T2DM.
Moriya T, et al. Diabetic Retinopathy and microalbuminuria can predict macroalbuminuria and renal
function decline in Japanese Type 2 diabetic patients. Diabetes Care.
MANAGEMENT
• Prevention
• Treatment
PREVENTION
• Intensive blood glucose control : target HbA1c
level < 7%1
• Intensive blood pressure control : target blood
pressure 130/80 mmHg1
• Renin-angiotensin system blockade : not
recommended2
1. Gross JL, et al. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care, 28:
176-88, 2005
2. National Kidney Foundation> KDOQI clinical practice guideline for diabetes and ckd: 2012
update. Am J Kidney Dis. 2012;60(5):850-86
TREATMENT
• Diet intervention
• Intensive blood glucose control
• Intensive blood pressure treatment and renin-
angiotensin system blockade
• Dyslipidemia
Gross JL, et al. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes
Care, 28: 176-88, 2005
DIET INTERVENTION
• Reduction of protein intake may improve
measures of renal function (urine albumin
excretion rate, GFR) :
– to 0.8 – 1.0 g/kg/day in DM and the earlier stages
of CKD
– to 0.8 g/kg/day in the later stages of CKD. (C)

36(S1):S11-66, 2013
INTENSIVE BLOOD GLUCOSE CONTROL
• Glycemic control : target HbA1c ~ 7.0 % (1A) or
above in patient with comorbidities or limited life
expectancy and risk of hypoglycemia (2C).
1. American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care.

36(S1):S11-66, 2013
2. National Kidney Foundation> KDOQI clinical practice guideline for diabetes and ckd: 2012
Trence D, et al. Chapter 31 : Management of the diabetic patient with chronic kidney disease. In :
Floege J,et al. Comprehensive clinical nephrology. 4th ed. Missouri. 2010
INTENSIVE BLOOD PRESSURE
CONTROL AND ALBUMINURIA
• Not using an ACE-I or ARB for the primary prevention
of DKD in normotensive normoalbuminuric patients
with diabetes. (IA)
• Using an ACE-I or ARB in normotensive patients with
diabetes and albuminuria levels > 30 mg/g who are
at high risk of DKD or its progression. (2C)
National Kidney Foundation. KDOQI clinical practice guideline for diabetes and ckd: 2012 update.
Am J Kidney Dis. 2012;60(5):850-86
INTENSIVE BLOOD PRESSURE
CONTROL AND ALBUMINURIA
• Hypertensive people with diabetes and CKD stage 1-
4 should be treated with an ACE-I or ARB, usually in
combination with a diuretic. (A)
• Target blood pressure < 130/80 mmHg. (B)
National Kidney Foundation. KDOQI clinical practice guideline for diabetes and ckd. Am J Kidney
Dis. 2007;49(2):S1-S179
William ME, et al. Diabetic kidney disease: current challenges. In : Himmelfarb J, et al. Chronic
kidney disease, dialysis and transplantation. 3th ed. Philadelphia. 2010
DYSLIPIDEMIA
• Using LDL-C lowering medicines to reduce risk
of major atherosclerotic events.(1B)1
• Not initiating statin therapy in patients with
diabetes who are treated by dialysis.(1B)1
• Target LDL-C :
– CKD stage 1-4 : < 100 mg/dL
– < 70 mg/dL is a therapeutic option.(B)2
1. National Kidney Foundation. KDOQI clinical practice guideline for diabetes and ckd: 2012
2. National Kidney Foundation. KDOQI clinical practice guideline for diabetes and ckd. Am J Kidney
Dis. 2007;49(2):S1-S179
RENAL REPLACEMENT THERAPY
• Higher threshold is usually used in diabetics
(serum creatinine > 6 mg/dL or eGFR < 15
mL/menit) to start of dialysis.
Trence D, et al. Chapter 31 : Management of the diabetic patient with chronic kidney
disease. In : Floege J,et al. Comprehensive clinical nephrology. 4th ed. Missouri. 2010
Trence D, et al. Chapter 31 : Management of the diabetic patient with chronic kidney
disease. In : Floege J,et al. Comprehensive clinical nephrology. 4th ed. Missouri. 2010
THANK YOU

Diabetic Nephropathy Fariz

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DIABETIC NEPHROPATHY

Ahmad Fariz Malvi Zamzam Zein

Longo DL, et al. Harrison’s Principles of Internal Medicine. 18th edition.

American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care.

Stage Description GFR (mL/min/1.73

American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care.

American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care.

1. American Diabetes Association. Standards of medical care in diabetes-2013. Diabetes Care.

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