Diabetic control of ckd patient prof. megahed abo elmagd
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Diabetic control of ckd patient prof. megahed abo elmagd
- 1. Can We Really Stop DN Progression By M.M.ABUELMAGD
- 2. Primary diagnoses for patients who start dialysis Diabetes 50% Hypertension 27% Glomerulonephritis 13% Other 10% United States Renal Data System (USRDS) 2008 Annual Data Report
- 3. No DM No CKD DM but No CKD DM & CKD 0% 5% 10% 15% 20% 25% 30% 35% 10 Years All Cause Mortality Afkarian M et al., J Am Soc Nephrol. 2013 Feb;24(2):302-8
- 4. D.M. and the Kidney • Stages of Diabetic Nephropathy – Stage I – Hyperfiltration - increased blood flow through the kidney, early renal hypertrophy – Stage II - Glomerular lesions without clinically evident disease – Stage III - Incipient nephropathy with microalbuminuria - alb/cr ratio .03 - .3 or albumin 20-200 mcg/min on timed specimen
- 5. D.M. and the Kidney • Stages of Diabetic Nephropathy – Stage IV - Overt diabetic nephropathy with proteinuria >300 mg/24 hr, e GFR declining – Stage V – End stage renal disease (ESRD), creatinine clearance <15 ml/min,
- 6. Natural History of Renal Measures and Impairment in Diabetic Kidney Disease Albuminuria Overt proteinuria eGFR Albumin Courtesy of Mark E. Molitch, MD. eGFR(mL/min/1.73m2) 0 20 40 60 80 100 120 140 0 5 10 15 20 25 30 Duration of Diabetes (years) 0 100 200 300 400 500 600 UrinaryAlbumin(mg/24h)
- 7. CURRENT CHRONIC KIDNEY DISEASE (CKD) NOMENCLATURE USED BY KDIGO CKD
- 8. Blood pressure control and progression of diabetic nephropathy Bakris GL. Am J Kidney Dis 2000; 36: 646-61 -14 -12 -10 -8 -6 -4 -2 0 95 98 101 104 107 110 113 116 119 MBP (mmHg) ∆ GFR (ml/min/y) 130/85 140/90 HT untreated Target BP Goal: less than 130/80mm Hg
- 9. KDIGO Guidelines, December, 2012
- 10. B.P. Target KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3:136- 150. http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf Accessed February 26, 2013.
- 11. Impact of Glycemic control on rate of CKD progression HBA1c<7% 7-9% >9% -2 -1.8 -1.6 -1.4 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0 eGFR decline/year Lee CL, et al., Am J Nephrol 2013;38:19–26
- 12. Glycemic control and Incident CKD (GFR<60 ml/min) HBA1c6-7% 7-8% >8% 0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 3.0% 3.5% 4.0% Incident CKD Bash LD et al., Arch Intern Med. 2008 Dec 8;168(22):2440-7
- 15. Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
- 16. Pioglitazone AGARWAL R, et al., Kidney International, Vol. 68 (2005), pp. 285–292
- 17. DPP4 inhibitors UAE at 24 weeks -35% -30% -25% -20% -15% -10% -5% 0% Placebo Linagliptin P=0.036 Groop PH, et al., Diabetes Care 2013; 36: 3460-8.
- 18. DPP4 inhibitors 0.00% 2.00% 4.00% 6.00% 8.00% 10.00% 12.00% 14.00% 16.00% 18.00% P<0.05 Von Eynatten M, et al., Diabetogia. 2013; 56 (suppl 1): S364.
- 19. DPP4 inhibitors eGFR (ml/minute) -2.5 -2 -1.5 -1 -0.5 0 Placebo Linagliptin P<0.05 McGill JB, et al., Diab Vasc Dis Res 2014; 11: 34-40
- 20. The sodium-glucose cotransporter-2 (SGLT2) mechanism in the proximal tubule. Hiddo J.L. Heerspink et al. Circulation. 2016;134:752-772 Copyright © American Heart Association, Inc. All rights reserved.
- 21. Physiologic mechanisms implicated in the cardiovascular and renal protection with SGLT2 inhibition. Hiddo J.L. Heerspink et al. Circulation. 2016;134:752-772 Copyright © American Heart Association, Inc. All rights reserved.
- 22. The relationship between urinary glucose excretion and eGFR. Hiddo J.L. Heerspink et al. Circulation. 2016;134:752-772 Copyright © American Heart Association, Inc. All rights reserved.
- 23. Effects of SGLT2 inhibitors on GFR. The effects of canagliflozin (100 mg daily, square s; 300 mg daily, circles) versus glimepiride (triangles) in patients with preserved renal function (A) (Reproduced from Cefalu et al17with permission of the publisher. Hiddo J.L. Heerspink et al. Circulation. 2016;134:752-772 Copyright © American Heart Association, Inc. All rights reserved.
- 24. ANP levels in subjects with type 1 diabetes mellitus before and after treatment with an SGLT2 inhibitor. Hiddo J.L. Heerspink et al. Circulation. 2016;134:752-772 Copyright © American Heart Association, Inc. All rights reserved.
- 25. The renal-cardio hypothesis for cardiovascular protection with SGLT2 inhibition: a nephrocentric perspective. Hiddo J.L. Heerspink et al. Circulation. 2016;134:752-772 Copyright © American Heart Association, Inc. All rights reserved.
- 26. Nephrol Dial Transplant (July 2016) 31: 1036–1043 SGLT2 Inhibitors: Renoprotection
- 27. Nephrol Dial Transplant (July 2016) 31: 1036–1043 SGLT2 Inhibitors: Renoprotection
- 28. N Engl J Med. 2016 Jun 14. [Epub ahead of print] SGLT2 Inhibitor: Retarding The Progression of CKD EMPA-REG OUTCOME trial
- 29. Diabetologia (2016) 59:1333–1339 SGLT2 Inhibitor: Cardiorenal Benefits
- 30. Diabetes Care Volume 39, July 2016 SGLT2 Inhibitor: Cardiorenal Benefits
- 31. Kidney International (2016) 89, 524–526 SGLT2 Inhibitors: Renoprotection:
- 32. Nutrition, Metabolism & Cardiovascular Diseases (2016) 26, 361-373 DPP-4 Inhibitors: Nephroprotection
- 33. Kidney International (2016) 89, 1049–1061 DPP-4 Inhibitors Vs ARBs
- 34. Laboratory Investigation (2015) 95, 1174–1185 DPP-4 Inhibitors: Nephroprotection
- 35. Figure 1 Cell Metabolism 2016 24, 15-30DOI: (10.1016/j.cmet.2016.06.009) Copyright © 2016 Elsevier Inc. Terms and Conditions
- 36. Figure 2 Cell Metabolism 2016 24, 15-30DOI: (10.1016/j.cmet.2016.06.009) Copyright © 2016 Elsevier Inc. Terms and Conditions
- 37. Figure 3 Cell Metabolism 2016 24, 15-30DOI: (10.1016/j.cmet.2016.06.009) Copyright © 2016 Elsevier Inc. Terms and Conditions
- 38. Figure 4 Cell Metabolism 2016 24, 15-30DOI: (10.1016/j.cmet.2016.06.009) Copyright © 2016 Elsevier Inc. Terms and Conditions
- 39. Microvascular event definitions Event type Event definition – one or more of the below Microvascular events Renal • New onset of persistent macroalbuminuria • Persistent doubling of serum creatinine • Need for continuous renal replacement therapy • Death due to renal disease Eye • Need for retinal photocoagulation or treatment with intravitreal agents • Vitreous hemorrhage • Diabetes-related blindness Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
- 40. Time to first microvascular event The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; HR: hazard ratio. Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
- 41. Time to first renal event Macroalbuminuria, doubling of serum creatinine, ESRD, renal death The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; ESRD: end-stage renal disease; HR: hazard ratio. Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
- 42. Time to first eye event Photocoagulation or treatment with intravitreal agents, vitreous hemorrhage or blindness The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; HR: hazard ratio. Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
- 43. Hazard ratio (95% CI) P value Primary composite endpoint* 0.87 (0.78-0.97) 0.01 Expanded composite endpoint† 0.88 (0.81-0.96) 0.005 Death from any cause 0.85 (0.74-0.97) 0.02 CV death 0.78 (0.66-0.93) 0.007 Fatal or nonfatal MI 0.86 (0.73-1.00) 0.046 Nephropathy 0.78 (0.67-0.92) 0.003 Clinical Outcomes with Liraglutide 43 LEADER (N=9340) *CV death, nonfatal MI (including silent MI), or nonfatal stroke; †CV death, nonfatal MI (including silent MI), nonfatal stroke, coronary revascularization, and hospitalization for unstable angina or HF. CI, confidence interval; CV, cardiovascular; MI, myocardial infarction. Marso SP, et al. N Engl J Med. 2016 Jun 13. [Epub ahead of print] 0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 Favors liraglutide
- 44. J Diabetes.2016 Jun 1 Metformin: Nephroprotection
- 46. Hovind P, etal., Diabetes Care. 2003 Mar;26(3):911-6.
- 47. RESULTS:The 12-year cumulative risk of microalbuminuria was 18.9 % ( P < 0.0001) for current smokers and 15.1 % (P = 0.087) for ex-smokers, compared with 10.0 % for nonsmokers. The corresponding risks of macroalbuminuria were 14.4 % ( P < 0.0001), 6.1 % ( P = 0.082) and 4.7 % respectively. The 12-year cumulative risk of ESRD was 10.3 % (P < 0.0001) for current smokers and 10.0 % (P < 0.0001) for ex-smokers, compared with 5.6 % for nonsmokers. CONCLUSIONS: Current smoking is a risk factor for the progression of diabetic nephropathy and the risk increases with the increasing dose of smoking. Ex-smokers seem to carry a similar risk of progression of diabetic nephropathy as nonsmokers.
- 48. RESULTS:The 12-year cumulative risk of microalbuminuria was 18.9 % ( P < 0.0001) for current smokers and 15.1 % (P = 0.087) for ex- smokers, compared with 10.0 % for nonsmokers. The corresponding risks of macroalbuminuria were 14.4 % ( P < 0.0001), 6.1 % ( P = 0.082) and 4.7 % respectively. The 12-year cumulative risk of ESRD was 10.3 % (P < 0.0001) for current smokers and 10.0 % (P < 0.0001) for ex-smokers, compared with 5.6 % for nonsmokers. CONCLUSIONS: Current smoking is a risk factor for the progression of diabetic nephropathy and the risk increases with the increasing dose of smoking. Ex-smokers seem to carry a similar risk of progression of diabetic nephropathy as nonsmokers.
- 49. From logistic regression analysis, smoking (p=0.0012) emerged as the most important factor associated with progression of nephropathy, followed by packyears (p=0.011), HbA1c mean value at follow-up (p=0.024), and total cholesterol (p=0.038).
- 50. Antihyperglycemic Therapy in Adults with T2DM Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
- 51. Antihyperglycemic Therapy in Adults with T2DM Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
- 53. Conclusion • In D.N. – Blood pressure control is a mandate – RAS blockers are the group of choice – Blood sugar control may have +ve impact on CKD progression – Pioglitasone has antiproteinuric effect – DPP4 inhibitors (linagliptin) have antiproteinuric & renoprotective actions
- 54. Thank You
Notes de l'éditeur
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- &lt;number&gt; This slide illustrates the time course of the relationship between diabetic nephropathy and the development of CKD. In patients with diabetes, a gradual elevation of urinary albumin excretion occurs first. Urinary albumin 30 mg/24 h, or 30 mg/g of Cr, is designated microalbuminuria. Over time, albumin excretion gradually increases to and exceeds 300 mg/24 h. At this point, the patient is considered to have albuminuria After the development of albuminuria, eGFR gradually decreases over time. The time interval between the development of albuminuria and the development of CKD Stage 5 in most patients ranges between 10 to 20 years. This time interval provides opportunity for intervention to slow the rate of CKD progression.
- KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3:136-150. http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf Accessed February 26, 2013. CKD is defined as abnormalities of kidney structure or function, present for43 months, with implications for health &lt;number&gt;
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- Ultimately, more intensive insulin regimens may be required (see Figure 3.) Dashed arrow line on the left-hand side of the figure denotes the option of a more rapid progression from a 2-drug combination directly to multiple daily insulin doses, in those patients with severe hyperglycaemia (e.g. HbA1c ≥10.0-12.0%). Consider beginning with insulin if patient presents with severe hyperglycemia (≥300-350 mg/dl [≥16.7-19.4 mmol/l]; HbA1c ≥10.0-12.0%) with or without catabolic features (weight loss, ketosis, etc). &lt;number&gt;
- The sodium-glucose cotransporter-2 (SGLT2) mechanism in the proximal tubule. Modified from Bakris et al4 with permission of the publisher. Copyright © 2009, Elsevier.
- Physiologic mechanisms implicated in the cardiovascular and renal protection with SGLT2 inhibition. HbA1c indicates hemoglobin A1c; and SGLT2, sodium-glucose cotransporter-2.
- The relationship between urinary glucose excretion and eGFR. With worsening renal function impairment (eGFR), the change in urinary glucose excretion over 24 hours (UGE0-24h) diminishes. eGFR indicates estimated glomerular filtration rate; and UGE, urinary glucose excretion. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM334550.pdf70
- Effects of SGLT2 inhibitors on GFR. The effects of canagliflozin (100 mg daily, square s; 300 mg daily, circles) versus glimepiride (triangles) in patients with preserved renal function (A) (Reproduced from Cefalu et al17with permission of the publisher. Copyright © 2013, Elsevier); dapagliflozin (DAPA; 5 mg daily, squares; 10 mg daily, triangles) versus placebo (PBO) in patients with CKD (B) (Reproduced from Kohan et al15 with permission of the publisher. Copyright © 2014, Elsevier); and empagliflozin versus placebo in patients with enrolled in EMPA-REG OUTCOME (C) (Reproduced from Wanner et al73 with permission of the publisher. Copyright © 2016, Massachusetts Medical Society). CKD indicates chronic kidney disease; and eGFR, estimated glomerular filtration rate.
- ANP levels in subjects with type 1 diabetes mellitus before and after treatment with an SGLT2 inhibitor. Baseline levels of atrial natriuretic peptide levels (ANP, pg/mL) in 40 patients with type 1 diabetes mellitus and ether normofiltration (T1D-N: GFR&lt;135 mL·min–1·1.73 m–2) or hyperfiltration (T1D-H: GFR≥135 mL·min–1·1.73 m–2) at baseline (A); effects of empagliflozin 25 mg daily treatment for 8 weeks on ANP levels (B); effects of empagliflozin treatment 25 mg daily for 8 weeks on ANP levels in normofilterers (C) and in hyperfilterers (D). GFR indicates glomerular filtration rate; Pre-SGLT2i-Eu, pre dose (baseline) SGLT2i euglycemia; Pre-SGLT2i-Hyper, pre dose (baseline) SGLT2i hyperglycemia; Post-SGLT2i-Eu, post dose SGLT2i euglycemia; Post-SGLT2i-Hyper, post dose SGLT2i hyperglycemia; SGLT2, sodium-glucose cotransporter-2; T1D-N, T1D with normofiltration; and T1D-H, T1D with hyperfiltration. In this study we quantified ANP by using Sigma-Aldrich’s Atrial Natriuretic Peptide EIA kit. The EIA assay was performed by Eve Technologies Corp according to Sigma-Aldrich protocol. The assay sensitivity for ANP begins at 1.02 pg/mL.
- The renal-cardio hypothesis for cardiovascular protection with SGLT2 inhibition: a nephrocentric perspective. LV indicates left ventricular; and SGLT2, sodium-glucose cotransporter-2.
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- &lt;number&gt; Mechanisms Linking GLP-1 to Modulation of Inflammation GLP-1 secretion from EECs is alternatively stimulated or inhibited by pro-inflammatory stimuli. GLP-1 in turn may control inflammation locally in the intestine through engagement of GLP-1 receptors on intestinal intraepithelial lymphocytes (IELs). GLP-1 may also reduce inflammation in different peripheral organs indirectly through weight loss or improved glucose control, or by targeting GLP-1Rs expressed on populations of circulating immune cells. Alternatively, GLP-1R activation may directly reduce inflammation in organs and cell types expressing the GLP-1R. The dashed line linking GLP-1 to anti-inflammatory actions in distinct organs reflects current uncertainty as to whether these actions are possibly direct or largely indirect.
- &lt;number&gt; Direct and Indirect Actions of GLP-1 in the Heart and Blood Vessels The GLP-1R is expressed predominantly in the atrium of the heart. The localization of GLP-1R expression in blood vessels is less well understood. Some blood vessels express the GLP-1R within vascular smooth muscle, whereas potential GLP-1R expression in endothelial cell populations is less completely defined. The actions of GLP-1 on heart and blood vessels are shown, and may be direct or indirect, depending on the species and specific experimental paradigm examined.
- &lt;number&gt; GLP-1 Modifies CV Risk through Direct and Indirect Actions in Multiple Organs The targets for GLP-1 that may impact the risk of developing CV disease, and the consequences of GLP-1 action in specific tissues and cell types with CV implications, are shown.
- &lt;number&gt; The CV Safety of GLP-1R Agonists Based on results from the LEADER trial, sustained GLP-1R agonism in subjects with T2D at high risk for CV events produced a reduction in MACE events and CV mortality, balanced by gastrointestinal side effects, and lingering uncertainty about any possible associated increased risk of cancer. The CV benefit of GLP-1R agonists in obese non-diabetic subjects has not been established.
- Source: EAC Charter v.9.0/LEADER RM deck &lt;number&gt;
- Reference: LEADER RM deck Source: EOT 14.2.94/ID14202000_e_km_microvascular_fas.cgm HR: EOT 14.2.92/ID14201980 &lt;number&gt;
- Reference: LEADER RM deck Source: EOT 14.2.97/ID14202030_e_km_nephropathy_fas.cgm HR: EOT 14.2.97/ID14202010 &lt;number&gt;
- Reference: LEADER RM deck Source: EOT 14.2.119/ID14202280_e_km_retinopathy_fas.cgm HR: EOT 14.2.116/ID14202260 &lt;number&gt;
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- Here is an overview of the ADA’s new treatment algorithm for type 2 diabetes, moving from monotherapy, to dual therapy, to triple therapy, and then to combination injectable therapy. Lifestyle management is emphasized throughout the progression of care, and individualization based on efficacy, hypoglycemia risk, weight, side effects, and costs is recommended. It is important to note that the ADA’s full Standards of Care provides tables on the properties of these agents, as well as the costs associated with them. Please visit professional-dot-diabetes-org-slash-S-O-C for more information. Let’s take a closer look at the algorithm. [SLIDE]
- Starting with dual therapy, the algorithm has been updated this year to incorporate consideration of ASCVD at the point of dual therapy given results of recently published cardiovascular outcome trials. As noted in the algorithm, in patients who do not have atherosclerotic cardiovascular disease (ASCVD), consider a combination of metformin and any one of the preferred six treatment options: sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist, or basal insulin; the choice of which agent to add is based on drug specific effects and patient factors, as highlighted in Table 8.1 which will be highlighted in the next slide. For patients with ASCVD, add a second agent with evidence of cardiovascular risk reduction after consideration of drug-specific and patient factors. If A1C target is still not achieved after 3 months of dual therapy, proceed to a three-drug combination. Again, if A1C target is not achieved after ~3 months of triple therapy, proceed to combination injectable therapy. At each step, lifestyle management should be reinforced and medication-taking behavior assessed. [SLIDE]
- As mentioned in the previous slide, Table 8.1 was added this year to highlight patient-specific factors to consider when selecting antihyperglycemic treatments for adults with T2DM.This is difficult to read, but I just wanted to highlight the overall structure of the table and describe its contents. Considerations noted in the table include: efficacy, hypoglycemia risk, effects on weight, cardiovascular effects, treatment cost, route of administration, renal effects, and additional drug-specific considerations, such as notable black box warnings and unique drug side effects. [SLIDE] &lt;number&gt;