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ObésitéQuelles conséquences sur la fonction rénale?  Dr Vincent Bourquin - service de néphrologie - http://nephrohug.com
“Let me have men about me           that are fat, Sleek-headed men, and             such as sleep o’nights:Yond Cassius   ...
“In recent years, there has been an alarmingrise in the prevalence of chronic kidney disease that has parralleled the incr...
Source: Hall et coll Am J Med Sci 2002
“Increasing evidence suggests that obesity isa potentially important contributor to        the development of CKD.”       ...
Source: http://bouzou.wordpress.com
Evolution surpoids en Suisse                                                  40                                 8.1     5...
Obésité en Suisse                                    8.1%                            29.2%                                ...
“...it appears that the peak level in the adult overweight and obese segment     of the Swiss population may be reached in...
“Bien que la prévalence des maladies rénales en  relation avec l’obésité ne soit pas clairement définie, plusieurs études r...
“Four patients with massive obesity and the nephrotic syndrome were studied. In  each case the proteinuria decreased durin...
“In the following years, several case reports describing glomerulosclerosis in veryobese patients have been published, but...
“The degree of                                         50     albuminuriashowed piecewise log-                            ...
Japon                                                                                150N of ESRD                         ...
Japon“We found that BMI was associated with an increased risk of the development ofend stage of renal disease in men in th...
Suède “Overweight (BMI > 25) at age 20 wasassociated with a significant three-fold excess risk for chronic renal failure.” ...
Framingham Heart Study  “After mean follow-up of 18.5 years, 244participants (9.4%) developed kidneydisease. Body mass ind...
Physician’Health Study   “After an average 14-year follow-up, 1’377participants (12.4%) had a GFR less than 60 mL/  min/1....
National Health and Nutrition Examination Survey (NHANES II)  “The study found that those with morbidobesity had more than...
Hypertension Detection and Follow-up Program (HDFP) “In HDFP participants without CKD at baseline, the incidence of CKD at...
Obesity-related glomerulopathy“ORG was defined morphologically as focal segmental glomerulosclerosis and glomerulomegaly or...
Obesity-related glomerulopathy      glomérulosclérose segmentaire et focale             PAS x100                          ...
Obesity-related glomerulopathy  discrète sclérose mésangiale focale et lésions “diabétoïdes”                    PAS x250  ...
Obesity-related glomerulopathy     épaississement focal de la membrane basale              ME x2’500                      ...
Obesity-related glomerulopathy                glomérulomégalie               PAS x300                         PAS x300    ...
Glomérulopathie liée à                                                      HSF idiopathique                              ...
“Obesity has not only been suggested  to cause renal disease but also to    accelerate its deterioration.”     Source: Pro...
“In a cohort of 162 incident patients withbiopsy-proven immunoglobulin A (IgA)  nephropathy, the presence of an elevated B...
“BMI showed a very strong association      with outcome after renal transplantation. BMI was also associated   with an inc...
“Higher body-mass index and elevated  blood pressure independly increase thelong-term risk of renal-cell cancer in        ...
“The positive association between obesity and kidneydisease is a relationship that is both   complex and not yet fully    ...
The interrelationship between adiposity and maladaptive             changes in the heart and kidney               Dysfunct...
Hyperuricemia                  Sympathetic activation                    RAAS activation                    Oxydative stre...
Forces hémodynamiques  “Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined  by measuring inulin an...
Forces physiquescompression rénale extrinsèque et intrinsèque      Source: Hall et coll. Am J Med Sci 2002
“Abnormal kidney function, caused by increased   renal tubular reabsorption, initiatesvolume expansion and increased blood...
↑Tubular NaCl                         ReabsorptionObésité augmente réabsorption tubulaire du sodium...            Source: ...
“Les cytokines sécrétés par le tissu adipeux   (adipokines), induisent une hyperactivitésympathique par le biais de la lep...
Substances vasoactives et profibrosantesAngiotensine: Rôle important dans le développement et la progression de la néphropa...
vasoconstriction artériole afférente               Source: ?
Effet sur artériole                                    NE + NE              control           Insulin  insulin-induced vas...
leptine “The obese Zucker (ZDF-fa/fa) rat, with       has hyperinsulinaemia and  hyperlipidemia develops progressiverenal ...
leptine      “Normal rats infused with leptin    developed proteinuria and focal glomerulosclerosis. Interactions betweent...
Adiponectine“Adiponectin (ADPN), whose levels arereduced in obesity and insulin resistance, was      strongly implicated i...
Adiponectine    “ADPN-deficient mice exhibited   effacement and fusion of podocyte    foot process as well as increased alb...
Source: http://bouzou.wordpress.com
“Le traitement de choix des néphropathies  associées à l’obésité est la réduction du              poids corporel.”        ...
“There was significant correlation between    body weight loss and decrease in               proteinuria.”       17 obese p...
“In a small Japanese case series, 25 patientswith BMI > 25 who were hypertensive and  microalbuminuric with preserved rena...
Source: Kuiper J.J. Nephron 1996
“En présence d’une hyperfiltration, d’une    hyperactivité du SRAA, a fortiori d’une        microalbuminurie ou d’une proté...
“17-year-old girl with morbid obesity (BMI 56.8) and ORG presenting with nephrotic range proteinuria,  who failed to impro...
“Obese patients with renal failure cansafely undergo bariatric surgery and that   bariatric surgery may have a role in tre...
© Chappatte
“BMI may not be ideal due to its inability to   reliably distinguish visceral obesity from  subcutaneous fat nor is able t...
“More studies are required to identify a   more reliable measure of kidneyfunction in the obese, but until then the use  o...
“Reverse epidemiology is a term for themedical hypothesis wich holds that the influence   of obesity and high body weightin...
“Higher BMI (up to 45) and higher serum      creatinine concentration were    incrementally and independentlyassociated wi...
merci de votre attentionDr Vincent Bourquin - service de néphrologie - http://nephrohug.com
Obésité, quelles conséquences sur la fonction rénale?
Obésité, quelles conséquences sur la fonction rénale?
Obésité, quelles conséquences sur la fonction rénale?
Obésité, quelles conséquences sur la fonction rénale?
Obésité, quelles conséquences sur la fonction rénale?
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Obésité, quelles conséquences sur la fonction rénale?

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Obésité, quelles conséquences sur la fonction rénale?

  1. 1. ObésitéQuelles conséquences sur la fonction rénale? Dr Vincent Bourquin - service de néphrologie - http://nephrohug.com
  2. 2. “Let me have men about me that are fat, Sleek-headed men, and such as sleep o’nights:Yond Cassius has a lean and hungry look; He thinks too much: such men are dangerous.”Source: Julius Caesar, Act 1, Scene 2 William Shakespeare (1564-1616)
  3. 3. “In recent years, there has been an alarmingrise in the prevalence of chronic kidney disease that has parralleled the increase in the prevalence of obesity....” Source: Ting et coll. Nephron Clin Pract 2009
  4. 4. Source: Hall et coll Am J Med Sci 2002
  5. 5. “Increasing evidence suggests that obesity isa potentially important contributor to the development of CKD.” Source: Ting et coll. Nephron Clin Pract 2009
  6. 6. Source: http://bouzou.wordpress.com
  7. 7. Evolution surpoids en Suisse 40 8.1 5.4 30 20 24.9 29.2 10 1992 0 2007 BMI 25-30 BMI > 30 Source: http:bag.admin.ch
  8. 8. Obésité en Suisse 8.1% 29.2% 62.7%Population sans excès pondéral Excès pondéral (IMC > 25) Adipositié (IMC > 30) Source: http:bag.admin.ch
  9. 9. “...it appears that the peak level in the adult overweight and obese segment of the Swiss population may be reached in the near future, i.e. the nextfew years, or – under best circumstances – may have been passed already.” Source: http:bag.admin.ch
  10. 10. “Bien que la prévalence des maladies rénales en relation avec l’obésité ne soit pas clairement définie, plusieurs études récentes ont montréune corrélation significative entre l’IMC d’une part, et la survenue d’une protéinurie ou d’une insuffisance rénale d’autre part” Source: Mathieu et coll. Rev Med Suisse 2006
  11. 11. “Four patients with massive obesity and the nephrotic syndrome were studied. In each case the proteinuria decreased during dietary weight loss. A mesangial glomerulopathy was present in two patients.” Source: Weisinger et coll. Ann Intern Med 1974
  12. 12. “In the following years, several case reports describing glomerulosclerosis in veryobese patients have been published, but this entity was considered as rare and rather bizarre.” Source: Prof G. Wolf Contribution to Nephrology 2006
  13. 13. “The degree of 50 albuminuriashowed piecewise log- Albumin mg/L 10 linear relationship 5 with body mass index (P = 0.0001)” 15 20 25 30 35 40 45 50 Body mass index (kg/m2)5670 people older than 40 years Source: Metcalf et coll. Clin Chem 1992
  14. 14. Japon 150N of ESRD 112.5 75 37.5 < 21.0 21.0-23.1 23.2-25.4 0 25.5- BMI, kg/m2 Total Men Women Source: Iseki et coll. Kidney Int 2004
  15. 15. Japon“We found that BMI was associated with an increased risk of the development ofend stage of renal disease in men in the general population in Okinawa.”100’753 screenees, during follow-up 404 screenees developed ESRD Source: Iseki et coll. Kidney Int 2004
  16. 16. Suède “Overweight (BMI > 25) at age 20 wasassociated with a significant three-fold excess risk for chronic renal failure.” 926 case patients and 998 control subjects Source: Ejerblad et coll. J Am Soc Nephrol 2006
  17. 17. Framingham Heart Study “After mean follow-up of 18.5 years, 244participants (9.4%) developed kidneydisease. Body mass index with odds ratio 1.23 (95% CI 1.08-1.41).” 2’585 participants with baseline and follow-up examination Source: Ejerblad et coll. J Am Soc Nephrol 2006
  18. 18. Physician’Health Study “After an average 14-year follow-up, 1’377participants (12.4%) had a GFR less than 60 mL/ min/1.73 m2. Higher baseline BMI wasassociated consistently with increased risk for CKD (OR 1.45)” 11’104 initially healthy men provided a blood sample after 14 years Source: Iseki et coll. Kidney Int 2004
  19. 19. National Health and Nutrition Examination Survey (NHANES II) “The study found that those with morbidobesity had more than double the riskof CKD (OR 2.3) compared to normal weight individuals, independent of age, sex, race, smoking and physical activity.” 9’082 adults with an average follow-up of 13.2 years. Source: Stengel et coll. Epidemiology 2003
  20. 20. Hypertension Detection and Follow-up Program (HDFP) “In HDFP participants without CKD at baseline, the incidence of CKD at year 5 was 28% in the ideal-body-mass-index group, 31% inthe overweight group (OR 1.21) and 34% in the obese group (OR 1.40).” 5’897 hypertensive adults Source: Kramer et coll. Am J Kidney Dis 2005
  21. 21. Obesity-related glomerulopathy“ORG was defined morphologically as focal segmental glomerulosclerosis and glomerulomegaly or glomerulomegaly alone.” 6’818 native renal biopsies Source: Kambham et coll. Kidney Int 2001
  22. 22. Obesity-related glomerulopathy glomérulosclérose segmentaire et focale PAS x100 PAS x250 Source: Kambham et coll. Kidney Int 2001
  23. 23. Obesity-related glomerulopathy discrète sclérose mésangiale focale et lésions “diabétoïdes” PAS x250 PAS x300 Source: Kambham et coll. Kidney Int 2001
  24. 24. Obesity-related glomerulopathy épaississement focal de la membrane basale ME x2’500 ME x2’500 Source: Kambham et coll. Kidney Int 2001
  25. 25. Obesity-related glomerulopathy glomérulomégalie PAS x300 PAS x300 Source: Kambham et coll. Kidney Int 2001
  26. 26. Glomérulopathie liée à HSF idiopathique l’obésité Protéinurie d’ordre néphrotique 48 % 66 % Syndrome néphrotique 5.6 % 54 % Oedèmes 35 % 68 % Albumine sérique g/l 39 29cholestérol sérique mg/dl 229 335 Sclérose focale 10 % 39 % Glomérulomégalie 100 % 10 % Fusion podocytaire 40 % 75 % ORG is distinct from idiopathic FSGS Source: Kambham et coll. Kidney Int 2001
  27. 27. “Obesity has not only been suggested to cause renal disease but also to accelerate its deterioration.” Source: Prof G. Wolf Contribution to Nephrology 2006
  28. 28. “In a cohort of 162 incident patients withbiopsy-proven immunoglobulin A (IgA) nephropathy, the presence of an elevated BMI at RBI was significantly associated with the severity of pathological renal lesions.” Maladie de Berger Source: Bonnet et coll. Am J Kidney Dis 2000
  29. 29. “BMI showed a very strong association with outcome after renal transplantation. BMI was also associated with an increased risk for delayed graft function...” 51’927 primary, adult renal transplant registred in the USRDS Source: Meier-Kriesche et coll. Transplantation 2002
  30. 30. “Higher body-mass index and elevated blood pressure independly increase thelong-term risk of renal-cell cancer in men.” 363’992 Swedish men Source: Bergström et coll. Br J Cancer 2001
  31. 31. “The positive association between obesity and kidneydisease is a relationship that is both complex and not yet fully understood.” Source: Ting et coll. Nephron Clin Pract 2009
  32. 32. The interrelationship between adiposity and maladaptive changes in the heart and kidney Dysfunctional adipose tissue •Macrophage infiltration •Low-grade inflammation ↑ Aldosterone •Increased IL-1, IL-6, TNF-α ↑ Angiotensin II •Elevated leptin NADP oxydase Source: Kuiper J.J. Nephron 1996 ROS production
  33. 33. Hyperuricemia Sympathetic activation RAAS activation Oxydative stress Inflammation Microalbuminuria Hyperfiltration progressing to: Endothelial dysfunction •Na-retention ↑ ROS NO ➠ ↑NOO- •Glomerular sclerosis ↓Bioavailable NO •Tubulointerstitial fibrosis ↑PAI-1/TPA •Proteinuria (impaired fibrinolysis •Decreased GFR vasoconstriction) ↓Delivery of glucose and insuline to tissuesHyperfiltration-related maladaptive mechanisms Source: Sowers et coll. Cardiorenal Med 2011
  34. 34. Forces hémodynamiques “Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined by measuring inulin and PAH clearance. In theobese group, GFR exceeded the control value by61% and RPF by 32%. Consequently, filtration fraction (FF) was increased.” (GFR)/(RPF) = (FF) Source: Chagnac et coll. J Am Soc Nephrol 2003
  35. 35. Forces physiquescompression rénale extrinsèque et intrinsèque Source: Hall et coll. Am J Med Sci 2002
  36. 36. “Abnormal kidney function, caused by increased renal tubular reabsorption, initiatesvolume expansion and increased blood pressureduring excess weight gain, and the hypertension and metabolic abnormalities associated with obesity, in turn, contribute to chronic renal disease.” Source: Hall JE Hypertension 2003
  37. 37. ↑Tubular NaCl ReabsorptionObésité augmente réabsorption tubulaire du sodium... Source: Hall JE Hypertension 2003
  38. 38. “Les cytokines sécrétés par le tissu adipeux (adipokines), induisent une hyperactivitésympathique par le biais de la leptine, et un étatinflammatoire de bas grade qui contribue au développement de lésions de scléroseglomérulaire, d’autant qu’il existe une résistance à l’adiponectine.” Source: Prof M. Laville Nephro Ther 2011
  39. 39. Substances vasoactives et profibrosantesAngiotensine: Rôle important dans le développement et la progression de la néphropathie. Effet sur l’hypertensionintraglomérulaire et la perméabilité sélective de la membrane basale glomérulaire.Insuline: Stimule la synthèse facteurs de croissance, tels que IGF-1 et 2, promoteurs probable d’hypertrophieglomérulaire.Vasodilatation artériole afférente, augmentation hypertension intraglomérulaire.Rénine: Augmentation, ainsi que l’aldostérone.Leptine: Action pro-inflammatoires et profibrotique. Rôle dans la survenue de l’hypertension chez sujet obèse.Stimulation du système sympathique.Transforming growth factor-β (TGF-β): AugmentationTumor necrosis factor-α (TNF-α): AugmentationPlasminogen activator inhibitor-1 (PAI-1): AugmentationInterleukine-6: AugmentationRésistine: Augmentation. Insulinrésistance, inflammation.Adiponectine: Diminution sous l’influence de la fétuine avec insulinorésistance, inflammation, dysfonctionendothéliale, stimulation SRAA et finalement HTA. Régulation perméabilité glomérulaire. Source: Mathieu et coll. Rev Med Suisse 2006
  40. 40. vasoconstriction artériole afférente Source: ?
  41. 41. Effet sur artériole NE + NE control Insulin insulin-induced vasodilatationSource: Juncos et coll. J Clin Invest 1993
  42. 42. leptine “The obese Zucker (ZDF-fa/fa) rat, with has hyperinsulinaemia and hyperlipidemia develops progressiverenal failure associated with an accentuated podocyte injury and glomerulosclerosis.” rat Zucker porteur d’une mutation du gène de la leptine Source: Hoshi and coll. Lab Invest 2002
  43. 43. leptine “Normal rats infused with leptin developed proteinuria and focal glomerulosclerosis. Interactions betweenthe activated RAAS and leptin appear toplay an important role in oxidative stress within endothelial cells and contribute to the pathogenesis of atherosclerosis.” Source: Correia et coll. Curr Opin Nephrol Hypertension 2004
  44. 44. Adiponectine“Adiponectin (ADPN), whose levels arereduced in obesity and insulin resistance, was strongly implicated in the pathogenesis of kidney injury in obesity.” Source: Sharma et coll. J Clin Invest 2008
  45. 45. Adiponectine “ADPN-deficient mice exhibited effacement and fusion of podocyte foot process as well as increased albuminuria. Administration of ADPN led toattenuation in podocyte damage together with a reduction in albuminuria.” Source: Sharma et coll. J Clin Invest 2008
  46. 46. Source: http://bouzou.wordpress.com
  47. 47. “Le traitement de choix des néphropathies associées à l’obésité est la réduction du poids corporel.” Source: Mathieu et coll. Rev Med Suisse 2006
  48. 48. “There was significant correlation between body weight loss and decrease in proteinuria.” 17 obese patients with proteinuria > 1g/day Source: Praga et coll. Nephron 1995
  49. 49. “In a small Japanese case series, 25 patientswith BMI > 25 who were hypertensive and microalbuminuric with preserved renal function were place in a low-caloric diet (25 kcal/kg) with significant improvment inmicroalbumuria and blood pressure over 1-year follow-up in the 12 patients who achieved a weight reduction of at least 5%.” Source: Ohashi et coll. Nippon Jinzo Gakkai Shi 2001
  50. 50. Source: Kuiper J.J. Nephron 1996
  51. 51. “En présence d’une hyperfiltration, d’une hyperactivité du SRAA, a fortiori d’une microalbuminurie ou d’une protéinurie,l’administration d’inhibiteur de l’enzyme de conversion est logique. Cependant, leur effet sur la protéinurie peut n’être que transitoire en l’absence de perte de poids stable, ce qui limite leur action néphroprotectrice.” Source: Praga et coll. Nephrol Dial Transplant 2001
  52. 52. “17-year-old girl with morbid obesity (BMI 56.8) and ORG presenting with nephrotic range proteinuria, who failed to improve following treatment with diet, exercise and ACEi/ARB therapy. Laparoscopic gastric bypass surgery was performed, and within 2 weeks following thesurgery, the patient had lost 5.7 kg body weight andshowed a remarkable decrease in protein excretion to one tenth of pre-surgery levels.” Source: Fowler et coll. Pediatr Nephrol 2009
  53. 53. “Obese patients with renal failure cansafely undergo bariatric surgery and that bariatric surgery may have a role in treating chronic kidney disease in select morbidly obese patients..” Source: Tafti et coll. Obes Surg 2009
  54. 54. © Chappatte
  55. 55. “BMI may not be ideal due to its inability to reliably distinguish visceral obesity from subcutaneous fat nor is able to differentiate a high body weight due to muscle mass from fat (or oedema).” Source: Ting et coll. Nephron Clin Pract 2009
  56. 56. “More studies are required to identify a more reliable measure of kidneyfunction in the obese, but until then the use of non-corrected GFR in combination with calibrated serum creatinine has been recommended in these individuals.” Source: Ting et coll. Nephron Clin Pract 2009
  57. 57. “Reverse epidemiology is a term for themedical hypothesis wich holds that the influence of obesity and high body weightindexes may be protective and associated with greater survival in obese patient in haemodialysis.” Source: R Stolic Med Hypotheses 2010
  58. 58. “Higher BMI (up to 45) and higher serum creatinine concentration were incrementally and independentlyassociated with greater survival, even after extensive multivariate adjustment for availablesurrogates of nutritional status and inflammation. ” 5-year cohort of 121’762 patients receiving HD 3x/week Source: Kalantar-Zadeh et coll. Mayo Clin Proc 2010
  59. 59. merci de votre attentionDr Vincent Bourquin - service de néphrologie - http://nephrohug.com

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