Diabetes Mellitus

1. DIABETIC
NEPHROPATHY
DR. RAVI PATEL

2. INTRODUCTION

3. • Global public health problem affects 300 million
people worldwide & expected to 552 million by 2030
• Global mortality is 5.1 million per year majority from
cardiovascular disease
(1 Death every 6 seconds)
• India has largest number of diabetics in the world.
25-40% of these develop End Stage Renal Disease.
• One of the most serious microvascular complication
of DM
• DN occur in T1DM, T2DM & other forms of Diabetes

4. DEFINITION

5. • Structural & Functional renal damage
manifested as clinically detected Albuminuria
in the presence of normal or abnormal GFR
• Triad:- Albuminuria
(>300mg/24h or >300mg/gm of creatinine)
HTN
Declining renal function (GFR)

6. RISK FACTORS

7. • Inadequate Glucose Control
• High blood pressure
• Dyslipidemia
• Genetic Factor
• Smoking
• Pregnancy
• Age
• Race

8. Natural History of Kidney
Disease In Diabetic
Nephropathy
5 STAGES

9. Time (yrs) 0 5 20 30
Onset of
Diabetes
Onset of
Proteinuria
End Stage
Renal
Disease
Hypertension
OVERT NEPHROPATHY
Rising S Cr,
Decreasing GFR
INCIPIENT NEPHROPATHY
Hyperfiltration,
microalbuminuria,
rising blood pressure
PRECLINICAL
NEPHROPATHY

11. Stage 1 (Early Diabetes)
• Hyperglycemia leads to increased kidney
filtration (Hyperfiltration)
• This is due to osmotic load and toxic effects of
high sugar levels on kidney cells
• Increased Glomerular Filtration Rate
(GFR >90ml/min) with enlarged kidneys

12. Stage 2 (Developing Diabetes)
• Clinically silent phase with continued hyperfiltration
and hypertrophy
• The GFR remains elevated or has returned to normal
(GFR 60-89ml/min) but glomerular damage has
progressed to significant microalbuminuria.
(30-300mg/24hr)
• Significant microalbuminuria will progress to end-
stage renal disease (ESRD).
• Therefore, all diabetes patients should be screened
for microalbuminuria on a routine basis.

13. Stage 3 (Overt Diabetes)
• Glomerular damage has progressed to clinical
albuminuria (>300mg/24h) with
GFR 30-59ml/min.
• Basement membrane thickening due to AGEP
(Advanced glycation end products)
• Urine is “Dipstick positive"
• Hypertension typically develops during this
stage

14. Stage 4 (Late-stage Diabetes)
• 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 this
stage.

15. Stage 5 (ESRD or CKD)
• GFR has fallen to <15 ml/min and renal
replacement therapy required (hemodialysis,
peritoneal dialysis, kidney transplantation)

16. Luis-Rodríguez D, Martínez-Castelao A, Górriz JL, Álvaro FD, Navarro-González JF. Pathophysiological role and
therapeutic implications of inflammation in diabetic nephropathy. World J Diabetes 2012; 3(1): 7-18

17. SCREENING METHODS

18. Algorithm
Urine dipstick for protein
(a) Type 1 : 5 years afterdiagnosis
or earlier in the presence of other
cardiovascular risk factos
(b) Type 2 : at the time of diagnosis
NEGATIVE POSITIVE
(urine protein >300mg/l)
on 2 separate occasions (exclude
other causes e.g. UTI, CCF etc.)
Overt nephropathy
Quantify excretion rate
e.g. 24-hr urine protein
POSITIVE
Screen for microalbuminuria
on early morning spot urine
Retest twice in 3 –6 months (exclude
other causes e.g. UTI, CCF etc.)
NEGATIVE
If 2 of 3 tests are positive, diagnosis
of microalbuminuria is established
3-6 monthly follow-up of
microalbuminuria
Optimise glycaemic control
Strict BP control
ACEI/ARB
Stop smoking
Lifestyle modification
Treat hyperlipidaemia
Avoid excessive protein
intake
Monitor renal function
Monitor for other diabetic
endorgan damage
Yearly test

19. Albumin Excretion
SPECIMEN COLLECTED
24hr collection
(mg/24h)
Timed collection
(μg/min)
First voided morning specimen
UrineAlbumin
concentration
(mg/l)
Urine ACR
Albumin:Creatinine
ratio* (mg/gm)
Normoalbuminuria <30 <20 <20 <30
Microalbuminuria 30-300 20-200 20-200 30-300
Overt proteinuria >300 >200 >200 >300

20. Microalbuminuria
• 1st sign of nephropathy
• 30-300mg/24hr Urine sample
• Powerful predictor of CVD and mortality
• Earlier 80% pts progress to clinical
albuminuria but due to multifactorial
intervention this has reduced to 20%.

21. Clinical Albuminuria
• Sensitive marker of CKD & CVD
• 1st indicator of DN
• >300mg/24hr Urine sample
• Increase transglomerular pressure gradient
Loss of negative charged in GBM
Increase GBM pore size
• Majority pts progress to ESRD

22. Increases AER Decreases AER
 Strenuous exercise
 Poorly controlled DM
 Heart failure
 UTI
 Acute febrile illness
 Uncontrolled HTN
 Haematuria
 Menstruation
 Pregnancy
 NSAIDs
 ACE inhibitors
 ARBs
Factors affecting urinary albumin excretion

23. Other Markers
• Cystatin C
• Transferrin
• Type IV collagen
• Ceruloplasmin
• Fibronectin
• NGAL(Neutrophil gelatinase associated lipocalin)
• KIM
• Liver fatty acid binding protein
• B-microglobulin
• A-1 macroglobulin

24. MANAGEMENT

25. • Glycemic control
• Blood pressure control
• Blood lipid modifiers
• Dietary protein & salt restriction
• Smoking cessation
• Management of anemia
• Fluid management
• Cardiovascular disease screening
• No Nephrotoxics (NSAIDS, Contrast,Aminoglycosides)
• Drug dose adjustment
• Options of renal replacement
• Treat infections properly
• Vaccination
• Early referral to Nephrologist

27. Diabetes Mellitus
• Drugs contraindicated: Metformin
• Preferably not used: Glibenclamide
• Can be used: Glimiperide, Glipizide,
Repaglinide, Pioglitazone,
• Preferable: Insulin, SGLT 2 inhibitors, DPP4
inhibitors, GLP1 analogues
Target : HbA1c <7 %, FBS: <100 mg/dl, PPBS<140 mg/dl

28. Hypertension
Systemic BP reduction Intra-glomerular BP reduction
Anti-proteinuric effect
Blood pressure control
Beta blockers
Alpha -blockers
Vasodilators
ARB
ACEi
Preservation of other target organs Preservation of kidneys
Target BP <130/80 mmHg

29. Recommendations
• Nonpregnant patient with micro- or macroalbuminuria either ACE inhibitors
or ARBs should be used (A)
• In patients with type 1 diabetes, hypertension, and any degree of
albuminuria, ACE inhibitors have been shown to delay progression of
nephropathy (A)
• In patients with type 2 diabetes, hypertension, and
microalbuminuria, Both ACE inhibitors and ARBs have been
shown to delay progression to macroalbuminuria (A)
• Reduction of protein intake may improve measures of renal function (urine
albumin excretion rate, GFR)
• When ACE inhibitors, ARBs, or Diuretics are used, monitor serum creatinine,
potassium levels for development of acute kidney disease, hyperkalemia.

30. Anemia
• May occur when GFR < 50 % & almost always
present when GFR < 30 %
• Correct deficiencies
Iron, Folic acid, Vit B12, Pyridoxine
• Erythropoietin 75 - 150 IU/kg SC
– With Iron supplements
– Expensive therapy Rs. 8 - 10, 000 / month
– Hb % maintained at 11 – 12
– > 13 in pts with CAD

31. Vaccination
• Hepatitis B
• Pneumococcal vaccine
• Influenza vaccine

32. Fluid management
Many diabetics have nephrotic state and severe
edema and need salt & fluid restriction
600 - 800 ml / day
equal to UOP
• Severe edema
• Mild to moderate
• No edema UOP + insensible
losses

33. Renal Replacement Therapy
• Hemodialysis
• Peritoneal dialysis
• Renal transplantation

34. Peritoneal dialysis
Advantages
• Slow, gentle
• Round the clock clearance
• Greater salt, fluid and
dietary freedom
• Mobility
• No need for vascular
access
Disadvantages
• Metabolic problems and some
mechanical problems
• Peritonitis