DIABETIC NEPHROPATHY

DIABETIC NEPHROPATHY

 Diabetic nephropathy is a clinical syndrome characterized by the

following:
• Persistent albuminuria (>300 mg/d or >200 μg/min) that is
confirmed on at least 2 occasions 3-6 months apart
• Progressive decline in the GFR
• Elevated arterial blood pressure
• In the 1930s, Kimmelstiel and Wilson described the classic
lesions of nodular glomerulosclerosis in diabetes associated
with proteinuria and hypertension.
DIABETIC KIDNEY

 The kidney may be damaged by diabetes in three main ways

- Glomerular damage
- Ischaemia resulting from hypertrophy of afferent and
efferent arterioles
- Ascending infection
PATHOPHYSIOLOGY

 Poor glycemic control damage the kidneys

 When the kidneys are damaged by diabetes afferent arterioles

become vasodilated to a greater extent than efferent arterioles

 This increases the intra-glomerular pressure which damage the

glomerular capillaries

 This process eventually leads to glomerular sclerosis resulting in

leakage of large molecules such as proteins in to urine
STAGES OF DIABETIC NEPHROPATHY
 Diabetic Nephropathy progresses through five predictable
stages which are as follows:-

Stage 1 (very early diabetes )

• Above-normal GFR.(>90 ml/min ) with enlarged kidneys
• Hyperglycemia leads to hyper-filtration due to osmotic
load and to toxic effects of high sugar on kidney cells
STAGES OF DIABETIC NEPHROPATHY contd….

Stage 2 (developing)

Silent phase with

• Continued hyperfiltration and hypertrophy
• The GFR remains elevated or has returned to normal
(GFR 60-89ml/min)
• Glomerular damage has progressed to significant
microalbuminuria
STAGES OF DIABETIC NEPHROPATHY contd….

Stage 3 (overt, or dipstick-positive)

• Glomerular damage has progressed to clinical albuminuria

more than 300 mg /day
• GFR 30-59ml/min .
• Basement membrane thickening
• Hypertension typically develops during stage
STAGES OF DIABETIC NEPHROPATHY contd….

Stage 4 (late-stage)

• Glomerular damage continues, with increasing amounts of

protein albumin in the urine.
• The kidneys’ filtering ability has begun to decline steadily, and
blood urea nitrogen (BUN) and creatinine (Cr) has begun to
increase.
• The glomerular filtration rate (GFR) decreases further more
with ( GFR 15-29ml/min ).
• Almost all patients have hypertension at stage 4
STAGES OF DIABETIC NEPHROPATHY contd….

Stage 5 (ESRD)

• GFR has fallen to <15 ml/min and renal replacement

therapy (i.e., haemodialysis, peritoneal dialysis, kidney
transplantation) is needed.
eGFR = estimated glomerular filtration rate
* Kidney damage defined as abnormalities on pathologic, urine, blood, or
imaging tests.
RISK FACTORS OF DIABETIC NEPHROPATHY
 Genetic Factors
 Inadequate Glucose Control
 High blood pressure
 Hyperlipidemia
 Smoking
 Long Standing Diabetes
 Pregnancy
 Poor nutrition during pregnancy
 Overweight
 Unhealthy diet
 Physical inactivity
 Ethnicity
EARLY DETECTION OF DIABETIC NEPHROPATHY
 Recently, attention has been called to atypical presentations
of diabetic nephropathy with dissociation of proteinuria from
reduced kidney function.

 Also noted is that microalbuminuria is not always predictive of

diabetic nephropathy.
MICROALBUMINURIA
 In the past, persistent microalbuminuria was the most studied
biomarker in diabetic nephropathy.

 Both the presence and the incremental changes in

microalbuminuria had been shown to correlate with the
development and progression of chronic kidney disease in
diabetic patients.

 Furthermore, microalbuminuria was also shown to be a risk factor

for the development of macrovascular complications in diabetic
patients
CHALLENGES OF MICROALBUMINURIA
 high variability,
 low sensitivity and specificity in predicting kidney disease
progression in diabetic nephropathy.
 spontaneous remission of MA could occur in more than half
of diabetic patients.
 Furthermore, 20% of type 2 diabetic patients had their
GFR decline to ≤60 mL/ min/1.73 m2 before or even
without passing the stage of microalbuminuria.
 Progression diabetic nephropathy is not necessarily parallel
with progression of urinary albumin excretion
CHALLENGES OF MICROALBUMINURIA contd….
 Only a minority of patients with MA progress to proteinuria

 one third of patients with MA, progressive renal function

decline starts already at the onset of MA, not proteinuria.

 As a prognostic biomarker for progression of diabetic

nephropathy, microalbuminuria fails in terms of sensitivity and
specificity
DIAGNOSIS
 In old diabetic patients, urine for protein should be checked at
least once a year
 Albumin-creatinine ratio of urine samples should be tested
Normal value
-in men <2.5 mg/mmol
-in women <3.5 mg/mmol
 When protein in urine is detected, other possible causes
should be excluded and repeat test should be done after 3-6
months
TREATMENT

 Optimize glucose control to reduce risk or slow progression of

diabetic kidney disease.
 Optimize blood pressure control to reduce risk or slow
progression of diabetic kidney disease.
 For people with non-dialysis dependent diabetic kidney
disease, dietary protein intake should be ~0.8 g/kg body weight
per day.
 For patients on dialysis, higher levels of dietary protein intake
should be considered.
TREATMENT contd….
 In non-pregnant patients with diabetes and hypertension, either
an ACE inhibitor or ARB is recommended for those with
modestly elevated urinary albumin excretion (30–299 mg/g
creatinine) and is strongly recommended for patients w/ urinary
albumin excretion ≥300 mg/g creatinine and/or eGFR <60.

 When ACE inhibitors, ARBs, or diuretics are used, consider

monitoring serum creatinine & potassium levels for increased
creatinine or changes in potassium.
TREATMENT contd….
 Continued monitoring of UACR in patients with albuminuria on
an ACE inhibitor or ARB is reasonable to assess treatment
response & progression of diabetic kidney disease

 An ACE inhibitor or ARB isn’t recommended for primary

prevention of diabetic kidney disease in patients with diabetes
with normal BP, normal UACR (<30 mg/g creatinine) & normal
eGFR.

 When eGFR is <60, evaluate and manage potential

complications of CKD.
TREATMENT contd….
 If patients have eGFR <30, refer for evaluation for renal
replacement treatment.

 Promptly refer to a physician experienced in the care of DKD

for:
-Uncertainty about the etiology of disease
-Difficult management issues
-Rapidly progressing kidney disease
MANAGEMENT OF CKD IN DIABETES
eGFR Recommended
All patients Yearly measurement of creatinine, urinary albumin
excretion, potassium
45-60 Referral to a nephrologist if possibility for non-diabetic
kidney disease exists
Consider dose adjustment of medications
Monitor eGFR every 6 months
Monitor electrolytes, bicarbonate, hemoglobin, calcium,
phosphorus, parathyroid hormone at least yearly
Assure vitamin D sufficiency
Consider bone density testing
Referral for dietary counselling
MANAGEMENT OF CKD IN DIABETES contd…

eGFR Recommended
30-44 Monitor eGFR every 3 months
Monitor electrolytes, bicarbonate, calcium, phosphorus,
parathyroid hormone, hemoglobin, albumin
weight every 3–6 months
Consider need for dose adjustment of medications

<30 Referral to a nephrologist

PREVENTION OF DIABETIC NEPHROPATHY
 Good evidence suggests that early treatment delays or
prevents the onset of diabetic nephropathy.

 Regular outpatient follow-up is key in managing diabetic

nephropathy successfully.