Diabetic Nephropathy, pathophysiology and management, screening, treatment.

1. Diabetic Nephropathy:
Pathophysiology And
Management
By
Aiswarya Lekshmi
MSc Biomedical Science

2. Healthy kidney & Diabetes affected kidney
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3. Definition:-
Chronic condition characterized
by:
UAE
BP
GFR
No other renal/renal tract
disease
Presence of diabetic
retinopathy

4. Characteristics of Diabetic nephropathy
Chronic complications of diabetes
Kidney disease in diabetic patients
ECM
Albuminuria
No symptoms for 5-10
ESRD
ESRD
CVD

5. ©www.hdcn.com
Develops in 35 - 45% of Type 1 diabetic patients
 20 - 30% of Type 2 diabetic patients

6. Progression Of Diabetic NephropathyProgression of Type 2 Diabetes
(Wada & Makino, 2013)

7. (Mogenson’s classification)
 Stages of development of nephropathy in type 2 diabetes
 Stage 1: Hyperfiltration
 Stage 2 : The Silent Stage
 Stage 3: Incipient nephropathy /Microalbuminuria
 Stage 4 : Macroalbuminuria/Overt Nephropathy
 Stage 5: Uremia

8. Pathophysiology
Metabolic pathway
Haemodynamic pathway
Genetic
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9. Glucose-dependent processes involved in diabetic nephropathy
Glucose induced tissue injury via AGEs
Polyol pathway
Activation of protein kinase C

10. Interactions between the pathogenic pathways of diabetic nephropathy
(Wada & Makino, 2013)

11. Management of Diabetic Nephropathy
Screening
Treatment

12. Screening
Laboratory tests to order at the initial diagnosis of diabetes
Laboratory tests for diabetic nephropathy
Urinalysis (dipstick)
Microalbuminuria
Proteinuria
Creatinine (Serum/Plasma)
Creatinine clearance (urine)
Creatinine (12- or 24 h urine)
Cystatin C (serum or plasma)
Kidney ultrasound
Kidney Biopsy
Urinary proteome analysis

13. Albuminuria thresholds for 3 common tests of diabetic nephropathy
(Shumway & Gambert, 2002)
Category 24-h Urine
Collection
(mg/24
hours)
Albumin:creatini
ne ratio, spot
collection
(μg/mg)
Albuminuria,
timed
collection
(μg/min)
Normal <30 <30 <20
Microalbuminuria 30–300 30–300 20–200
Macroalbuminuria >300 >300 >200

14. Treatment strategies
 Glycaemic control
 Lifestyle modification
 Blood pressure control
 Cholesterol control
 Combination therapy
 Dialysis
 Transplantation

15. Suggested pathophysiological mechanisms
Mechanism Treatment
Metabolic
Hyperglycaemia Insulin*
Increased glucose-derived proteins (eg, AGE) Aminoguanidine↠AGE cross-
linkbreakers (eg, PTB‡)
Polyol Aldose reductase inhibitors†
Mechanical/hormonal
Elevated systemic blood pressure Antihypertensive drugs*
Increased intraglomerular pressure
ACE inhibition*, low protein diets*
Increased vasoactive hormones (eg,
angiotensin-II, endothelin)
ACE inhibition* angiotensin-II
antagonists† . ET receptor antagonists‡
Intermediate pathways
Growth factors eg, TGFb, IGF Antibodies‡
Protein kinase C dependent PKCβ inhibition‡
* Proven clinically
† Proven experimentally and now under investigation in human beings
‡ Under experimental investigation. TGF=transforming growth factor; IGF=insulin like growth factor; AGE=advanced glycated end
products; ACE=angiotensin converting enzyme; T=endothelin; PTB=phenacylthiazolium bromide; PKC=protein kinase C

16. Online Diabetes Self-management System
www.jmir.org
www.jmir.org

17. SUMMARY
• Tight control of blood glucose
• Tight control of blood pressure
• Therapies - single pathways inhibitors
• Future - New therapeutic approaches targeting
multiple pathways

18. References
Chen, L., Chuang, L.-M., Chang, C.-H., Wang, C.-S., Wang, I. C., Chung, Y., Peng, H.-Y., Chen, H.-C., Hsu, Y.-L., Lin, Y.-S.,
Chen, H.-J., Chang, T.-C., Jiang, Y.-D., Lee, H.-C., Tan, C.-T., Chang, H.-L. and Lai, F. (2013) 'Evaluating self-management
behaviors of diabetic patients in a telehealthcare program: longitudinal study over 18 months.' Journal Of Medical
Internet Research, 15(12) pp. e266-e266.
Cooper, M. E. (1998) 'Pathogenesis, prevention, and treatment of diabetic nephropathy.' Lancet, 352(9123) pp. 213-
219.
Ratner, R. E. (2001) 'Glycemic control in the prevention of diabetic complications.' Clinical Cornerstone, 4(2)
pp. 24-37.
Salem, J. K. and Hoogwerf, B. J. (1996) 'Diabetic nephropathy: strategies for preventing renal failure.'
Cleveland Clinic Journal Of Medicine, 63(6) pp. 331-338.
Shumway, J. T. and Gambert, S. R. (2002) 'Diabetic nephropathy-pathophysiology and management.' International
Urology And Nephrology, 34(2) pp. 257-264.
Vivian, E. M. and Rubinstein, G. B. (2002) 'Pharmacologic management of diabetic nephropathy.' Clinical
Therapeutics, 24(11) pp. 1741-1756.
Wada, J. and Makino, H. (2013) 'Inflammation and the pathogenesis of diabetic nephropathy.' Clinical Science
(London, England: 1979), 124(3) pp. 139-152.
Waanders, F., Visser, F. W. and Gans, R. O. B. (2013) 'Current concepts in the management of diabetic
nephropathy.' The Netherlands Journal Of Medicine, 71(9) pp. 448-458.