Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 1
JAFAR AL-SAID. M.B.CHB. MD. FASN. FACP.CHAIR OF INTERNAL MEDICINE.NEPHROLOGY AND INTERNAL MEDICINE CONSULTANT.BAHRAIN SPECIALIST HOSPITAL.
Diabetic Nephropathy
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 2
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 3
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 4
• Introduction.• Epidemiology.• Pathogenesis. • Progression. • Diagnosis. • Management.
Scheme
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 5
Historical Points• 18th Century Proteinuria was recognized in DM.
• 1930 Kimmelstiel and Wilson described the typical nodular glomerular lesion in Dm with Proteinuria.
• 1950 Kidney disease was recognized as DM complication.
• Current Leading cause of ESRD in USA and western societies.
BatumanVecihi, Khardori Romesh, et. Al. Diabetic Nephropathy: Background, Pathophysiology, Etiology Medscape. Updated: Jul 31, 2015
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 6
20-40% of DM patient will develop Nephropathy.
In the presence of Minimal Albuminuria > 300mg/dl It will develop in:
• 80% of DM I.
• 20-40% of DM II.
Introduction
Suma Dronavalli, Irena Duka, George L. Bakris. The Pathogenesis of Diabetic Nephropathy Posted: 08/01/2008; Nat Clin Pract Endocrinol Metab CME © 2008. http://www.medscape.org/viewarticle/577156
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 7
Definition
A syndrome characterized in diabetics by 2 of the following:
• Persistent albuminuria > 300mg/day. On at least to occasions 3 -6m apart. • Progressive decline in GFR.• Elevated BP.
BatumanVecihi, Khardori Romesh, et. Al. Diabetic Nephropathy: Background, Pathophysiology, Etiology Medscape. Updated: Jul 31, 2015
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 8Hypertension Dyslipidemia Kidney Disease Blindness0%
10%
20%
30%
40%
50%
60%
70%
80% 71% 65%
44%
28%
Comorbid conditions
Distribution of NHANES participants with diabetes, self-reported cardiovascular disease, & single-sample markers of CKD, 2007-2012
Data Source: National Health and Nutrition Examination Survey (NHANES), 1988–1994, 1999-2004 & 2007–2012 participants aged 20 & older. Cardiovascular disease designation is based on self-report of any CVD. CKD is defined as eGFR <60 or ACR ≥30.
Prevalence of Diabetic with CKD. NHANES. Adults 2012.
USRDS 2015
9Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016
Prevalence of CKD by age & risk factor among NHANES participants, 1998-2012
National Health and Nutrition Examination Survey (NHANES), 1988–1994, 1999-2004 & 2007–2012 participants aged 20 & older.
Diabetes defined as either HbA1c >7%, self-reported, or currently taking glucose-lowering medications.
Hypertension defined as BP ≥130/≥80 for those with diabetes or CKD, otherwise BP ≥140/≥90, or taking medication for hypertension.
10Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016
Distribution of markers of CKD in
NHANES participants with
diabetes, hypertension, self-
reported cardiovascular disease,
& obesity, 2007–2012
National Health and Nutrition Examination Survey (NHANES), 2007–2012 participants aged 20 & older. Single-sample estimates of eGFR & ACR; eGFR calculated using the CKD-EPI equation.
11Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 12
Trends in annual number of ESRD incident cases (in thousands), by primary cause of ESRD, in the U.S. population, 1996-2013
ESRD Incidence by cause
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 13
ESRD prevalence by cause
Trends in annual number of prevalent ESRD cases (in thousands), by primary cause of ESRD, in the U.S. population, 1996-2013
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 14
Trends in adjusted* prevalence (per million) of ESRD,by primary cause of ESRD, in the U.S. population, 1996-2013
ESRD Prevalence per populationBy cause
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 15
Functional
Structural ESRD
Progression
Hemodynamic changes
Thickening of GBM. Mesangial expiation.Glom. hypertrophy
Irreversible Scarring
Hypertension. Decreased eGFR.
Proteinuria.
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 16
Microalbuminuria
Macroalbuminuria?
Steinke JM et al. (2005) The early natural history of nephropathy in type 1 diabetes: III. Predictors of 5-year urinary albumin excretion rate patterns in initially normoalbuminuric patients. Diabetes54:2164-2171
Progression
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 17
<30mgNormal
30-300mg
Moderate
>300mg
Sever
Albuminuria as continuum value
Microalbuminuria
KDIGO Reference 22
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 18
• Is a continuum.
• Varies according to:• Time.• Physical Activity.• Fever.• Blood pressure.• Labs variation. • Dietary Prot. intake.
•
Albuminuria
Tuttle K, Bakris G. et. al. Diabetic Kidney Disease: A Report From an ADA Consensus Conference. Diabetes Care 2014;37:2864–2883 | DOI: 10.2337/dc14-129
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 19
Hemodynamic
GeneticMetabolic
Factors Contributing to development of Diabetic Nephropathy
Nephropathy
Ziyadeh FN (2004) Mediators of diabetic renal disease: the case for TGF-â as the major mediator. J Am Soc Nephrol 15 (Suppl 1): S55-S57
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 20
Decreased ResistanceAfferent > Efferent
Increased intraglomerular pressure
.Mechanical strain.
.Albumin leak. Mesangial expansion..GBM thickness.Podocytes injury
Hemodynamic Pathway
• Prostanoid.• NO2.• VEGF.• RAAS.• Endothilin.• TGF-B1.
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 21
Glycosylation End
Products
PKC
Hyperglycemia Injury
Mesangial Matrix expansion.Cell apoptosis.Increased Podocyte Permeability
VEGFTGFB1
Over expression GLUT 1,4
Friedman EA (1999) Advanced glycation endproducts in diabetic nephropathy. Nephrol Dial Transplant 14 (Suppl 3): S1-S9.Porte D Jr and Schwartz (1996) MW Diabetes complications: why is glucose potentially toxic? Science 272: 699-700.Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414: 813-820.
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 22
Glycosylation End Products
Glucose
+Amino A.Proteins.
Advanced glycosylation end products
Microvascular Complications
Makita Z et al. (1991) Advanced glycosylation end products in patients with diabetic nephropathy.N Engl J Med 325: 836-842Singh AK et al. (1998) Effect of glycated proteins on the matrix of glomerular epithelial cells. J Am Soc Nephrol 9: 802-810
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 23
Protein Kinase C
Oxidative stressDiacyglycerol
Hyperglycemia
Activation
PKC TGF B1
Mesangial ExpansionGBM thickening
Yamagishi S et al. (2007) Molecular mechanisms of diabetic nephropathy and its therapeutic intervention. Curr Drug Targets 8: 952-959
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 24
TGF-B1
Hyperglycemia
Increase expression of TGF-
B1
Cellular Hypertrophy.Collagen Synthesis
Sharma K et al. (1999) Captopril-induced reduction of serum levels of transforming growth factor-â1 correlates with long-term renoprotection in insulindependent diabetic patients. Am J Kidney Dis. 34:818-823Sharma K and Ziyadeh FN (1995) Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator. Diabetes 44: 1139-1146
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 25
Pathogenesis of Diabetic Nephropathy
BatumanVecihi, Khardori Romesh, et. Al. Diabetic Nephropathy: Background, Pathophysiology, Etiology Medscape. Updated: Jul 31, 2015
MetabolicHemodynamic
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 26
• Diabetic Nephropathy is more common within first degree relatives.
Among Pima Indian developed Overt Proteinuria:• 14 % neither parents had Proteinuria. • 23% one parent had proteinuria.• 46% both parents had proteinuria.
Genetic susceptibility
Trevisan R and Viberti G (1995) Genetic factors in the development of diabetic nephropathy. J Lab Clin Med 126: 342-349.Pettitt DJ et al. (1990) Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 33: 438-443.
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 27
Susceptibility loci for Microvascular complication on Chromosomes: 3, 7, 9, 20.
Diabetic Nephropathy susceptible gene areas on chromosomes:• 7q21.3• 10p15.3• 14q23.1• 18q22.3
Genetic susceptibility
Imperatore G et al. (1998) Sib-pair linkage analysis for susceptibility genes for microvascular complications among Pima Indians with type 2 diabetes. Pima Diabetes Genes Group. Diabetes 47: 821-830.
Vardarli I et al. (2002) Gene for susceptibility to diabetic nephropathy in type 2 diabetes maps to 18q223-23. Kidney Int 62: 2176-2183.
Iyengar SK et al. (2007) Genome-wide scans for diabetic nephropathy and albuminuria in multiethnic populations: the family investigation of nephropathy and diabetes (FIND). Diabetes 56: 1577-1585
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 28
Pathology
• ECM expansion.• Mesangial expansion.• Kimmelstiel-Wilson nodule.• Arteriolar Hyalinosis.• Glomerular sclerosis. • Thickening of GBM.• Thickening of TBM.
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 29
DMCVD
CKD
Which one started first ??
High CV risk patient
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 30
DM + CKDCoronary
Art. disease
CVD risk Assessment
=Tonelli M, Muntner P, Lloyd A, et al.; Alberta Kidney Disease Network. Risk of coronary events in people with chronic kidney diseasecompared with those with diabetes: a population level cohort study. Lancet 2012;380:807–814
AtherosclerosisAMI.Cardiac fibrosis.Art. Calcification.
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 31
• Absence of retinopathy.• Rapid decrease eGFR.• Rapidly increasing Proteinuria.• Refractory HTN.• Active urinary sediments.• > 30% reduction of GFR with RAAS. • Clinical picture for other systemic disease.
Increased possibility of causes other than DM leading to the kidney disease:
National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendationsfor Diabetes and Chronic Kidney Disease. Am J Kidney Dis 2007;49(Suppl. 2) S12–S154
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 32
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 33
Management of Diabetic Nephropathy
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 34
Multidisciplinary Approach
Internist
Nephrologist
Patient
Endocrinologist
Dietician
Social worker
Cardiologist
Nurse
Pharmacist
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 35
• Lifestyle.•BP. •DM. • Lipids. •Depression.•Compliance.
Managing Diabetic Nephropathy
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 36
Certain points to be considered:• Fluid intake. • Salt intake. 5 gm daily. (Na 2.3 gm).• Protein. Recommended 0.8gm/kg daily. • Hyperkalemia. • Acid/Base. • Malnutrition. • Anemia.• PTH, Vit. D, Ca & PO4.
Dietary Remarks in Diabetic Kidney Disease
Tuttle K., Bakris G. Diabetic Kidney Disease: A report from an ADA Consensus. Diabetes Care. Vol. 37, Oct 2014
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 37
Target BP in Diabetic patient
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 38
Target BP < 140/90mmHg in diabetic CKD. < 130/80mmHg with Alb./Creat. > 30mg/day
Diastolic < 60mmHg was associated with higher ESRD.
Diastolic < 65mmHg was associated with poor CV outcome.
Hypertension in Diabetic patients
• Wheeler DC, Becker GJ. Summary of KDIGO guideline. What do we really know about management of blood pressure in patients with chronic kidney disease? Kidney Int 2013;83: 377–383
• James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311: 507–520
Peralta CA, Norris KC, Li S, et al.; KEEP Investigators. Blood pressure components and end-stage renal disease in persons with chronic kidney disease: the Kidney Early Evaluation Program (KEEP). Arch Intern Med 2012;172:41–47
Kovesdy CP, Bleyer AJ, Molnar MZ, et al. Blood pressure and mortality in U.S. veterans with chronic kidney disease: a cohort study. Ann Intern Med 2013;159:233–24
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 39
• ACE inh. & ARB reduce the progression of kidney disease.
• This is specifically true in CKD III or higher with significant proteinuria.
• CONTRAINDICATED TO USE COMBINATION ACE inh. and ARB.
RAAS in CKD with DM
Fried LF, Emanuele N, Zhang JH, et al.; VA NEPHRON-D Investigators. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 2013;369:1892–1903
Parving H-H, Brenner BM, McMurray JJV, et al.; ALTITUDE Investigators. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012;367:2204–2213
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 40
Department of Public Health and Clinical Medicine, Medicine, Umeå University, SE-901 87Umeå, Sweden Correspondence to: M Brunström [email protected] Additional material is published online only. To view please visit the journal online. Cite this as: BMJ 2016;352:i717http://dx.doi.org/10.1136/bmj.i717. Accepted: 12 January 2016
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 41
Aim: Assess the CV mortality and morbidity in DM with different BP targets.
Design: Meta-analysis. (Central, Medline, Ebase, Biosis.)
Eligibility:• RCT > 100 with DM. • Treated for > 12 months.• Comparing two agents.• Two target BP.• One versus two drugs.
Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses
BMJ 2016;352:i717 | doi: 10.1136/bmj.i717
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 42
Results:49 Trials.N = 73 738 participant.
Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic
review and meta-analyses
Base Line BP mmHg
all cause mortality RR (95%CI)
CV mortalityRR (95%CI)
MIRR (95%CI)
StrokeRR (95%CI)
ESRDRR (95%CI)
>150 0.89 (0.8-0.99) 0.75 (0.36-0.87)
0.74 (0.63-0.87)
0.77 (0.65-0.91)
0.82 (0.71-0.94)
140-150
0.87 (0.78-0.98) 0.84 (0.76- 0.93)
<140 1.05 (0.95-1.16) 1.15 (1- 1.32)BMJ 2016;352:i717 | doi: 10.1136/bmj.i717
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 43
Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses
Results from meta-analyses stratified according tobaseline systolic blood pressure (SB P), reported for eachoutcome separately
BMJ 2016;352:i717 | doi: 10.1136/bmj.i717
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 44
Aim: Control of BP among CKD and DM and Medication.
Hypertension Management and Cardiovascular risk Factors Among Chronic Kidney Disease Patients with Diabetes
Jafar Al-Said, M.B. CHb. MD. FASN, FACP. Soni Murdeshwar. Bahrain Specialist Hospital ESH Annual meeting 2014
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 45
Hypertension Management and Cardiovascular risk Factors Among Chronic Kidney Disease Patients with Diabetes
Jafar Al-Said, M.B. CHb. MD. FASN, FACP. Soni Murdeshwar. Bahrain Specialist Hospital ESH Annual meeting 2014
Matching:
CV risk profile:
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 46
Hypertension Management and Cardiovascular risk Factors Among Chronic Kidney Disease Patients with Diabetes
Jafar Al-Said, M.B. CHb. MD. FASN, FACP. Soni Murdeshwar. Bahrain Specialist Hospital ESH Annual meeting 2014
BP changes over follow up:
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 47
Number of AnitHTN. Medications:
Hypertension Management and Cardiovascular risk Factors Among Chronic Kidney Disease Patients with Diabetes
Jafar Al-Said, M.B. CHb. MD. FASN, FACP. Soni Murdeshwar. Bahrain Specialist Hospital ESH Annual meeting 2014
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 48
Hypertension Management and Cardiovascular risk Factors Among Chronic Kidney Disease Patients with Diabetes
Jafar Al-Said, M.B. CHb. MD. FASN, FACP. Soni Murdeshwar. Bahrain Specialist Hospital ESH Annual meeting 2014
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 49
Control of Sugar in Diabetic Nephropathy
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 50
Increased incidence with eGFR < 60ml/min
Causes:• Prolonged action of Insulin.• Prolonged action of oral hypoglycemic agents. • Chronic Malnutrition.• Acute Calorie deprivation.• Alcohol intake.• Deficient Gluconeogenic precursor.
Hypoglycemic incidence in CKD
Tuttle K, Bakris G. et. al. Diabetic Kidney Disease: A Report From an ADA Consensus Conference. Diabetes Care 2014;37:2864–2883 | DOI: 10.2337/dc14-1296
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 51
Decreased precision in CKD due to:• Shorter RBC life span.• Acid/Base.• Anemia. • Using Erythrocyte stimulating factors.
HbA1C in CKD
Vos FE, Schollum JB, Coulter CV, Doyle TCA, Duffull SB, Walker RJ. Red blood cell survival in long-term dialysis patients. Am J Kidney Dis 2011;58:591–598.
Nakao T, Matsumoto H, Okada T, et al. Influence of erythropoietin treatment on hemoglobin A1c levels in patients with chronic renal failure on hemodialysis. Intern Med 1998;37:826–830
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 52
Optimal survival with HbA1C for ESRD 7-8%.
U curve of HbA1C.
Shurraw S, Hemmelgarn B, Lin M, et al.; Alberta Kidney Disease Network. Association between glycemic control and adverse outcomes in people with diabetes mellitus and chronic kidney disease: a population-based cohort study. Arch Intern Med 2011;171:1920–1927
Kalantar-Zadeh K. A critical evaluation of glycated protein parameters in advanced nephropathy:a matter of life or death: A1C remains the gold standard outcome predictor indiabetic dialysis patients. Diabetes Care 2012;35:1625–1628.
Ramirez SPB, McCullough KP, Thumma JR, et al. Hemoglobin A(1c) levels and mortality in the diabetic hemodialysis population: findings from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Diabetes Care 2012;35: 2527–2532
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 53
• HbA1C.• Fructosamine. • 1,5 anhydroglucitol.• Glycated Albumin.
Glycemic markers
Kim WJ, Park C-Y, Lee K-B, et al. Serum 1,5-anhydroglucitol concentrations are a reliable index of glycemic control in type 2 diabetes with mild or moderate renal dysfunction. Diabetes Care 2012;35:281–286.
Inaba M, Okuno S, Kumeda Y, et al.; Osaka CKD Expert Research Group. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietininjection. J Am Soc Nephrol 2007;18:896–903
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 54
Metformin Dose adjustment according to eGFR
Tuttle K., Bakris G. et.al Diabetic Kidney Disease: A report from an ADA Consensus. Diabetes Care. 2014;37:2864–2883 | DOI: 10.2337/dc14-1296
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 55
Dose adjustment for Oral Hypoglycemic agents
Tuttle K, Bakris G. et. al. Diabetic Kidney Disease: A Report From an ADA Consensus Conference. Diabetes Care 2014;37:2864–2883 DOI: 10.2337/dc14-1296
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 56
• CKD I – IV SAME AS GENERAL POPULATION. <100mg/dl for LDL / 30-40% reduction from baseline.• ESRD. benefit is not confirmed with lipid
lowering.
• Statins recommended for all diabetic CKD not on dialysis.
Hyperlipidemia in CKD
Palmer SC, Craig JC, Navaneethan SD, Tonelli M, Pellegrini F, Strippoli GFM. Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 2012;157:263–275.
Haynes R, Lewis D, Emberson J, et al. Effects of lowering LDL cholesterol on progression of kidney disease. J Am Soc Nephrol. 8 May 2014
Wanner C, Tonelli M, Cass A, et al. KDIGOclinical practice guideline for lipid management in CKD: summary of recommendation statementsand clinical approach to the patient. Kidney Int2014;85:130321309Reference 34
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 57
Incidence 15-25%.Causes:• Steroid.• Calcineurin inh. (Tacrolimus).• Increased Appetite. • Wt. Gain.
Outcome:Increased CV risk.Reduce graft survival.
New Onset Post Transplant Diabetes
Sarno G, Mehta RJ, Guardado-Mendoza R,Jimenez-Ceja LM, De Rosa P, Muscogiuri G. New-onset diabetes mellitus: predictive factors and impact on the outcome of patients undergoing liver transplantation. Curr Diabetes Rev 2013;9:78–85.
Chakkera HA, Mandarino LJ. Calcineurin inhibition and new-onset diabetes mellitus aftertransplantation. Transplantation 2013;95:647–652.
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 58
Management outcome of Chronic Kidney Disease in our Nephrology
OPD
JAFAR AL-SAID, TEERATH KUMAR, SONI MERDASHWAR BAHRAIN SPECIALIST HOSPITAL
• HTN and CV highlight Dec. 2012• ESH annual Meeting 2013
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 59
Aim of the Study
• What are the CV risk factors in CKD patients followed in our clinic?
• What is the rate of progression of their kidney function?
• What are the factors related to the final kidney function?
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 60
Methodology
Retrospective Observational. CKD patient followed in Nephrology OPD over 8.5 years (102month) from Oct. 2003 till April 2012.
Exclusion:1. Patient with only one visit. 2. No lab workup.3. Primary Glomerulonephritis. 4. Transplant.5. Pregnant.
Inclusion:1. Adult > 14 years.2. Had CKD.3. Followed in OPD.
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 61
Results• N = 245 patients.
• Mean follow up: 23.6 month (SE 1.6).
• Mean Age: 58.7 years (SE 0.9).
• Mean BMI: 30.9kg/m2 (SE 0.7)(SD10.5)
• Males: 60.8%
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 62
Cardiovascular risk factorsTotal CKD population, n = 245
HTN Hyperlipi. DM Hyperuric. IHD PVD Stroke0%
10%20%30%40%50%60%70%80%90%
100%91%
72%
60%
43%
20%9%
6%
Type of CV disease
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 63
Demographics of into DM and Non DM
DM Non DM P N 147 98
Age 61.8(0.9) 54(1.8) <0.0001Male
gender55% 69% 0.047
BMI 31.6(0.6) 30(1.4) 0.2
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 64
Dividing the total population into DM and Non DM
DM Non DM p
Mean of first eGFR (SE)
42.8 (1.8) 49.4(2.1) 0.02
Mean of Last eGFR (SE)
41(2.1) 51.2(3) 0.005
p 0.58 0.22
Difference in eGFR -0.9(1.7) -2.4(2) 0.5
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 65
Variables Correlation Coefficient
p
Systolic1 -0.2 0.012Hb1 0.36 0.001Alb1 0.25 0.03Follow up duration
0.23 0.008
Systolic2 -0.19 0.03Hb2 0.4 0.001Alb2 0.27 0.025PO4 2 -0.4 0.004Beta blocker -0.19 0.025Ca-block -0.22 0.012Vasodilator -0.23 0.007NTG -0.26 0.002
Correlation of the last eGFR with demographic factors, CV risk factors and the medications used in DM
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 66
S.Cr and eGFR changes over follow up in HTN and DM subgroups
Non HTN & Non DM (SE)
Non HTN & DM (SE)
HTN & Non DM (SE)
HTN & DM (SE)
P
First Cr 1.4 (0.1) 1.8 (0.34)
1.8 (0.1) 1.9 (0.08) <0.001
Last Cr 1.3 (0.09)
1.8 (0.5) 1.9 (0.14) 2.3 (0.16) 0.5
p 0.07 0.75 0.35 0.05First
eGFR 58.7 (4.2) 52.8 (10.7) 47.8 (2.7) 42.2 (1.8) 0.3
Last eGFR
59.2 (4.6) 61.7 (13.5) 49.9 (3.7) 39.6 (2.1) 0.1
P 0.18 0.13 0.3 0.8
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 67HTN DM0%
10%20%30%40%50%60%70%80%90%
100% 87%
55%
ESRD with HD at Bahrain specialist Hospital N = 118 patients
Jafar Al-Said. GCC Diabetes Conference Bahrain March 2016 68
• Diabetic Nephropathy occur in 20-40% of patients with Dm.• Its manifestation require Genetic, Hemodynamic and Metabolic factors.• Growth factors and cytokines play major role in its development. • Proteinuria, decreased GFR and HTN are its main clinical features. • ESRD could develop in 40-80%.• Management require tight control of BP, sugar and lipids.
Conclusion