An updated overview of diabetic nephropathy - Jornadas... · An updated overview of diabetic nephropathy

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  • An updated overview of diabetic nephropathy

    Jess Egido MD, PhD Catedrtico de Medicina UAM

    Jefe del Servicio de Nefrologa e Hipertensin Director del Laboratorio de Patologa Renal y Vascular Fundacin

    Jimenez Daz. Madrid CIBERDEM

  • Tony Scully. S 2 | N AT U R E | VO L 4 8 5 | 1 7 M AY 2 0 1 2

    Diabetes Prevalence Exploding Globally Approximately 1/3 will Develop Nephropathy

    The estimated prevalence of T2DM by 2050 in de US is 1 in 3 adults

  • Diabetic nephropathy in type 1 diabetes: has the outlook improved since the 1980s?

    Marshall et al. Diabetologia (2012) 55:23012306

    Changing cumulative incidence of persistent proteinuria in type 1 diabetes by duration of diabetes

    Steno cohort, diagnosed before 1953 Pittsburgh cohort, diagnosed 19501980

    Intensively managed DCCT cohort, diagnosed 19781988

  • New terminology in renal diabetes field. Does it really matter?

    Former term New term

    Normoalbuminuria Microalbuminuria Macroalbuminuria severely increased albuminuria

    >300 mg/day or >300 mg/g

    moderately increased albuminuria 30 and 300 mg/day or between 30 and 300 mg/g

    Normal albuminuria

  • Berhane et al .Clin J Am Soc Nephrol 6: 24442451, 2011

    Quantitative albuminuria added to eGFR improves the risk for diabetes ESRD and death

    2420 type 2 diabetic Pima Indians followed 1982-2005 (mean 10.2 years). 287 individuals developed ESRD

    9.3 times than normo

  • Ten-year mortality in type 2 diabetes by kidney disease manifestation.

    Afkarian M et al, J Am Soc Nephrol 24: 302308, 2013

    15,064 participants in the NHANES III

  • Diagnosis of diabetic nephropathy

  • Clinical predictors of non-diabetic renal disease

    Lack of retinopathy Short duration of DM Hematuria (microscopic red blood cell [RBC]

    or dysmorphic RBC on urinanalysis) Less prominent proteinuria Lower glycosylated hemoglobin Other

  • He F et al Diabetologia (2013) 56:457466

    Proliferative diabetic retinopathy is a highly specific indicator for diabetic nephropathy.

  • CLASS I: Glomerular Basement Membrane Thickening ( mild or nonspecific LM changes) -GBM > 395 nm in females and > 430 nm in males

    >glomerular hyperfiltration

    Pathologic classification of diabetic nephropathy Renal pathology Society . JASN 2010

    CLASS IIa: Mild mesangial expansion in >25% of the observed mesangium . IIb: Severe mesangial expansion in >25% of the observed mesangium

    CLASS III: Nodular sclerosis (Kimmelstiel-Wilson lesions ), at least one convincing Kimmelstiel-Wilson lesions

    CLASS IV : Advanced diabetic glomeruloesclerosis ( Global glomerular sclerosis in > 50% of glomeruli)

    Interstitial and vascular lesions

  • The modern spectrum of renal biopsy findings in patients with diabetes

    Sharma SG et al. Clin J Am Soc Nephrol. 2013 Jul 25

    Among 2642 native kidney biopsies , 620 (23.5%) were from patients with diabetes (year 2011)

    Acute tubular necrosis, hypertensive nephrosclerosis and a myriad of glomerular lesions: focal segmental glomerulosclerosis, IgA nephropathy, and membranous nephropathy , among others

  • Diabetic nephropathy with superimposed IgA nephropathy

  • Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus

    Thakar Charuhas V. et al. Clin J Am Soc Nephrol 6: 25672572, 2011

    Frequency of reaching stage 4 CKD by patient groups.

    3679 diabetics followed 1999-2008; 1822 required at least one hospitalization ; 530 of 1822 patients experienced one AKI episode ;157>2 AKI

    Hazard ratio for reaching stage 4 CKD: AKI 3.56, proteinuria 3.54, hypertension 1.82

  • Normoalbuminuric chronic kidney disease (eGFR

  • 1. Strict control of blood glucose,blood pressure and lipids 2. Decreasing proteinuria beyond the RAS 3. Emergent therapies modulating intracelullar pathways

    Treatment approach in patients with diabetes kidney disease

    Nutritional management and physical activity are also key elements in patients with diabetes and CKD

  • Friedman et al. Clin J Am Soc Nephrol 8: 2013

    Short-term changes after a weight reduction intervention in advanced diabetic nephropathy

    36% reduction in albuminuria Significant reduction in serum creatinine

    Six obese individuals with advanced diabetic nephropathy (estimated GFR ,40 ml/min per 1.73 m2, urine albumin excretion >30 mg/d) . 12% reduction in weight (12 weeks)

  • Summary of recommendations for glycemic , blood pressure, and lipid control for most adults with diabetes. ADA 2012

    ADA .Diabetes Care; Jan 2012; 35. S11

  • Glycated Hemoglobin and the Risk of Kidney Disease in Adults

    11,357 participants followed for 14 years (ARIC Study)

    Stepwise logistic regression analysis model of DKD progression (n = 270)

    Nephrol Dial Transplant (2012) 27: 18471854

    A study of the natural history of diabetic kidney disease (DKD)

    Selvin et al.Diabetes 60:298305, 2011

  • Intensive vs conventional glucose therapy on Albuminuria in patients with diabetes and CKD. A KDOQI review

    Patients with type 1 or 2 diabetes; from 2003 to 2010; 5 studies (n =27,159)

    A Systematic Review for a KDOQI Clinical Practice Guideline Am J Kidney Dis. 2012. 60:747-769

  • Hyperglycemia control on renal function in patients with diabetes and CKD.

    A KDOQI review

    A Systematic Review for a KDOQI Clinical Practice Guideline

    A strict blood glucose control was associated with a 2.5-fold increase in severe hypoglycemia

  • The long-term risk of RENAL FAILURE was significantly lower on intensive vs conventional therapy

    The DCCT/EDIC Research Group*

    N Engl J Med. 2011 December 22; 365: 23662376

    1,441 patients with type I diabetes

    UKPDS 80 4309 patients T2DM, 17 years follow up reduction in cardiovascular lesions Post hoc ADVANCE trial ; 11,140 participants, intensive vs conventional , 5 years follow up

    Perkovic V et al. Kidney International (2013) 83, 51752

  • Am J Kidney Dis. 2012;60:850-886

  • microalbuminuria

    Vejakama P et al . Diabetologia 2012. 55:566578

    Reno-protective effects of reninangiotensin system blockade in type 2 diabetic patients: a systematic review and network meta-analysis

    ACEI/ARB vs

  • Vejakama P et al . Diabetologia 2012. 55:566578

    Reno-protective effects of reninangiotensin system blockade in type 2 diabetic patients: a systematic review and network meta-analysis

    Doubling of serum creatinine ACEI/ARB vs

    The same was seen on ESRD (End -Stage Renal Disease)

  • Decreasing residual proteinuria in Diabetes Kidney Disease

    Pentoxifylline :mean reduction 15% Omega -3 :mean reduction 18% Glycosaminoglycans (Sulodexide) :SunMACRO trial ,no effect Thiazolidinediones : mean reduction 24%; increase CV events

    Mineralcorticoid receptor antagonists :mean reduction 30-40% Endothelin antagonists :mean reduction 40% (Atrasentan Trial; SONAR) VDR activators (Paricalcitol): mean albuminuria reduction 28%

    The treatment with either ACEi or AT1R reduces proteinuria by 35%

  • The addition of Aldosterone antagonists to RAS blockers reduces proteinuria in diabetic and non diabetic CKD patients

    Navaneethan SD et al. Clin J Am Soc Nephrol 2009:4; 542-551

    A meta-analysis of 7 trials, 372 patients

    Increase risk of hyperkalemia. Need of long-term renal outcomes and


    % of patients with proteinuria reduction >50% of baseline values during follow up

    Morales E , Nephrol Dial Transplant 2013 ;28:405-12

    30 40 50 60 70 80 90


    1 6 12 24 36 48 Last visit



    All patients Diabetics eGFR

  • 2013

  • Diabetic retinopathy

    Atherosclerotic lesions

    Diabetic Nephropathy

    JAK/STAT pathway inhibitors in diabetic nephropathy

    With or without hyperlipidemic

    Diabetic mice

    Local administration of jak/stat inhibitors compounds

  • e-PREDICE Early Prevention of Diabetes Complications in Europe FP7-HEALTH-2011

    To assess the long-term effects of different therapeutic regimens, both

    pharmacological and lifestyle interventions, for the early prevention of

    diabetic complications in 3,000 people with intermediate hyperglycaemia

    and screen-detected diabetes.

    The biobank is located at IISFJD

  • Millions of high-risk people can avoid developing type 2

    diabetes by losing 7% of their body weight

  • Renal and Vascular Research Lab.

    Fundacin Jimnez Daz . Autnoma University. Madrid.