nephrology obesity and kideny

1. Eman Elrefaie
Obesity Related
Glomerulopathy
(ORG)

2. Obesity Related Glomerulopathy
 Introduction
 Definition
 Pathogenesis
 Predisposing factors
 Clinical manifestations
 Pathology
 D.D
 Treatment

3. Introduction

5. Obesity and ESKD
Ann. Intern. Med., 2006, 144: 21–28

6. • Obesity-driven glomerular hyperfiltration contributes to
glomerulomegaly, which can lead to the development of
proteinuria, secondary focal and segmental
glomerulosclerosis (FSGS) and progressive CKD .
• Occurring in patients with a body mass index (BMI) ≥30
kg/m2 .
Definition

7.  Mechanism of renal injury in obesity :
Pathogensis

8.  Mechanism of renal injury in obesity :
Pathogensis

9.  Isolated proteinuria with or without renal dysfunction is
the most typical initial symptom in ORG patients.
 Subnephrotic proteinuria (< 3.5 g/day), and
approximately 30% of patients reached nephrotic-range
proteinuria.
 Some patients had high levels of proteinuria but no
significant decrease in plasma albumin.
 Hypertension (50–75%) and Dyslipidemia (70–80%)
 Edema, are rarely presented in ORG patients.
Clinical Manifestations

10.  Long-term ORG patients have clinical manifestations of a
slow but steady increase in urinary protein
 The proportion of these patients progressing to(ESRD)
ranges from 10 to 33%
Clinical manifestations

11.  Predisposing factors for renal injury in obesity :
Predisposing factors

12.  Volume and density :
Pathology

13.  The major microscopic pathological change in ORG :
 Glomerular hypertrophy identified as an increased
obesity related glomerular diameter.
 The glomerular volume of ORG patients was
approximately three times that of the normal individuals.
 The glomerular density was lower.
 Some patients have a change of FSGS
pathology

14.  Among the five subtypes of FSGS, perihilar
glomerulosclerosis is the predominant subtype (which is
attributed to a main load elevation in perihilar vessels in
the context of obesity type )

15. 

16. Diagnostic criteria for ORG :
Diagnostic
criteria for ORG

17. Differential diagnosis
Glomerular changes of hypertensive nephropathy :
• Global glomerulosclerosis
• Smaller volume than the normal ones
• The remaining nephrons are compensatory
hypertrophy.
The typical pathological changes of diabetic
nephropathy :
• Mesangial expansion and glomerular basement
membrane thickening
 Hypertensive
nephropathy
 Diabetic
nephropathy
 primary FSGS

18. Changes in kideny with obesity
 The differences between obesity related FSGS and primary
FSGS

19. Treatment
Weight
loss
RAAS
Blockade
Hypoglycemic
drugs
Treatment for
lipid
metabolism
Novel
treatment

20. Diet (overeating or quality of food)
 Fructose (Sucrose, HFCS)
 Peer, alchol
 Purine rich food (meat, seafood)
 Plant foods ( such as vegetables )
 Nuts(especially walnuts)
 Marine lipid (omega3)
Examples of nutrients that promot
insulin resistance and fat
accumulation irrespective of its
calories
Examples of nutrients that counter
insulin resistance and fat
accumulation irrespective of its
calories
Nephro. Dial. Trasnplant., (2015 )1656–1664

21. 5 months of hypocaloric diet :
weight loss of 4%
proteinuria reduction of 30%
weight losses of >6%
proteinuria reduction of >60%
weight losses of >10%
proteinuria reductions of >70%
Diet-induced weight loss

22. .
 Significant improvement of proteinuria
following surgery
 Geometric mean of ACR was 74 mg/g at
baseline and decreased to 17 mg/g at
three years.

23. Bariatric surgery
Curr Opin Pediatr., 2018, 30(2): 241–246
Bariatric surgery has emerged
treatment option for those with severe
obesity and significant kidney disease

24. RAAS blockade
 Reduction of proteinuria in 86% of individual with obesity .
 Moreover, a long-term follow-up study noted that the antiproteinuric
effects of RAAS blockers were attenuated over time, especially in those
without any weight loss or even with weight gain

25. Hypoglycemic drugs
Dipeptidyl peptidase-4 inhibitors and glucagon-like
peptide-1 receptor agonists :
 Inhibited ORG development in HFDinduced ORG mouse
models
 Increasing systemic insulin sensitivity
 Suppressing local inflammation and podocyte autophagy
 Reducing monocyte and M1 macrophage infiltration
and TNF-α and IL-6 productions .
Metformin may be potentially therapeutic for ORG :
 Due to its antifibrotic effects

26.  INT-777: the selective agonist of G protein-coupled bile acid
receptor TGR5, could decrease proteinuria, podocyte injury,
mesangial expansion, fibrosis, and macrophage infiltration in the
kidneys.
 Lipoxin A4: an important down-regulator of IL-12 production,
was proven to be effective in attenuating the renal inflammatory
response and injury in the ORG mouse model via suppressing
the activation of NF-κB and ERK/p38 mitogen-activated protein
kinase (MAPK) pathways. Thereby, it may also be potentially
therapeutic for ORG
Treatment for lipid metabolism

27. Novel treatment

28. SS-31: A mitochondria-targeting antioxidant podocytes, inhibits
the upregulation of mesangial expansion, glomerular sclerosis
macrophage , prevents mitochondria from lipotoxicity.
Zinc: Downregulates P38 MAPK-mediated inflammatory responses
and slows down the progression of ORG .
 Curcumin : Reduces the leptin toxicity on podocytes by
inhibiting the Wnt/β-catenin signaling pathway
 mTOR inhibitors: Effective to reduce fat accumulation in the
kidneys
Novel Treatments

29. THANK YOU