boala diabetica de rinichi

8/3/2019 Boala Diabetica de Rinichi

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Diabetic Nephropathy


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Definition

A microvascular complication of diabetes

marked by albuminuria and a deterioratingcourse from normal renal function to ESRD.


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Current Terminology

Kidney, not Renal (or Reno)

CKD, not CRF DKD (= diabetic nephropathy)

AKI, not ARF

Still ESRD (End Stage Renal Disease) Still RRT (Renal Replacement Therapy)


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Redefinirea DKD

BRC aparuta la un pacient cu DZ

Dg: -macroalbuminurie, indiferent eRFG

-eRFG


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ESRD Incidence Counts and Rates

by Primary Diagnosis (USRDS, 2006)

Better CKDManagement?


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Importance of Diabetic Kidney Disease

Kidney disease as diabetic complication:

30% of Type 1 Diabetes40% of Type 2 Diabetes

CKD amplifies CVD risk of diabetes


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Pathology

Leziuni specifice

Leziuni nespecifice, dar cu frecventa maimare si evolutie particulara:

- macroangiopatia renala (ATS)

- nefroangioscleroza

- infectii


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Pathology DZ 1

Expansion of mesangial matrix with diffuseand nodular glomerulosclerosis

(Kimmelstiel-Wilson nodules) (40-50%) Thickening of glomerular and tubular BM Arteriosclerosis and hyalinosis of afferent

and efferent arterioles Tubulointerstitial fibrosis Progresia relativ uniforma a leziunilor


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Pathology DZ 2

Heterogenitate crescuta a leziunilor

Leziuni glomerulare caracteristice 30-50%

Aspect pseudonormal in MO 30%

Leziuni caract. altor BRC (GNC) 20-30%

Leziuni tubulo-interstitiale si vascularedisproportionat de severe

Atrofia tubulara, scleroza interstitiala-R ESRD


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Glomerulus = filtering unit


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Pathogenesis

Exposure to the diabetic milieu Hyperglycemia

Induce mesangial expansion and injury Increased activity of growth factors Activation of cytokines Formation of ROS accumulation of advanced glycosylation endproducts in

tissues Accumulation of ECM components, such ascollagen


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Pathogenesis

Genetic predisposition to or protection fromdiabetic nephropathy

Differences in prevalence of microalbuminuria,ESRD in different patient populations

Only half of patients with poor glycemic

control will develop diabetic nephropathyFamily studies

Multiple genes may be involved


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Clasificarea Mogensen

Stade 1 : hyperfiltration glomrulaire Augmentation du taux de filtration glomrulaire de plus de 25%Stade 2 : lsions histologiques

paississement de la membrane basale glomrulaire, dpthyalin dans les artrioles glomrulaires et expansion msangiale

Stade 3 : nphropathie dbutante Microalbuminurie:

30 mg/j300 mg/jRAC* : 2 mg/mmol20 mg/mmol chez lhomme

2,8 mg/mmol28 mg/mmol chez la femme

Stade 4 : nphropathie patente Diminution du taux de filtration glomrulaire Protinurie permanente:

Albuminurie 300 mg/jRAC : 20 mg/mmol chez lhomme

28 mg/mmol chez la femmeStade 5 : insuffisance rnale terminale (eRFG


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Natural History


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Diabetic Kidney Disease Screening WHEN

Type 1: after 5 years, then annuallyType 2: at diagnosis, then annually

HOWAlbumin-to-Creatinine ratio in random urine

Microalbuminuria = 30-300 mg/g Macroproteinuria

Estimate GFR (eGFR) from serum creatinine usingformulas

Retinopathy: useful clue


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Formulas for Estimating GFR

CKD-EPI Cockcroft-Gault

MDRD (Modification of Diet in Renal Disease Study) GFR calculator (www.kidney.org)

GFR depends on: Serum creatinine

Age Gender Race
http://www.kidney.org/http://www.kidney.org/


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Dg diferential

Indicatii PBR chiar daca DZ:

Absenta retinopatiei Hematuria macroscopica Durata DZ 1 sub 10 ani la debutul proteinuriei Elemente clinice sau bc ale unei afectari multisistemice Degradarea rapida a functiei renale (>2-3ml/min/luna)

Instalarea brusca a unui SN Azotemie (eRFG30% a eRFG in prima luna dupa introducerea IEC


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Interventions to Slow CKD Progression

Strong evidenceBlood pressure control

ACEI / ARBGlucose control in DM

Weaker evidence

Protein restrictionLowering LDL cholesterol


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Hypertension control:

Lower the BP, slower the decline in GFR inpatients with diabetic nephropathy

JNC VI recommended BP < 130/85 mmHg in

patients with renal insufficiencyPatients with CKD and > 1g proteinuria, BP

goal should be < 125-130/75-80 mmHg


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Hypertension control:

Linia I: IEC, BRA, diuretice tiazidice

Linia II: BCC, BB, alfa-blocante


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Glycemic control DCCT

1441 patients with type I DM randomly assigned to intensivetherapy vs. conventional therapy

Intensive therapy reduced microalbuminuria by 39% Reduced albuminuria by 54%

Tinta HbA1c < 7% (ADA), < 6.5% (IDF)

RepaglinidaInsulina


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Il est primordial de traiter la protinurie de faonvigoureuse pour rduire la pression intraglomrulaire etainsi freiner la dtrioration de la fonction rnale.

Lobjectif vis est une diminution de 60 % de la

protinurie initiale ou latteinte dun rapport

albumine/cratinine urinaire infrieur 30 mg/mmol.


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ACE inhibitors: Type I diabetes with nephropathy:

Lewis et al. NEJM, 1993. captopril vs. placebo50% RR of combined end points of death, dialysis and

transplantation in ACEI group independent of BP

Angiotensin-receptor blockers: RENAAL study(2001)

1513 pts with type II DM and nephropathy. Losartan vs.placebo. Losartan reduced the rate of doubling of cr by 16%but no effect on the rate of death.

IDNT(2001) 1715 type II DM pts with nephropathy. Irbesartan vs.

amlodipine vs. placebo. Irbesartan has 20% lower risk ofreaching endpoints compared to placebo and 23% lowerincidence than that in the amlodipine group


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Conclusions:

ACE inhibitors or ARB have a strong antiproteinuric effectapart from their antihypertensive actions

Increasing the dose of the ACEI or ARB beyond theoptimum antihypertensive doses further reducesproteinuria

Antiproteinuric effect is enhanced by a low Na diet ordiuretic

ACE inhibitors, ARBs, and nondihydropyridine calciumchannel blockers have a greater antiproteinuric effect thanother antihypertensive classes in hypertensive patients withDKD


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Target dietary protein intake : 0.8 g/kg / day


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Lowering LDL cholesterol:

- Target LDL-C in diabetes and CKD stages 1-4

should be < 100 mg/dL;


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Treatment - conclusions

Early screening Tight glycemic control

HTA management Use ACEI as first line, if not tolerated, use

ARB. Use the maximum dose as tolerated

If still hypertensive or proteinuric, considerusing combination ACEI and ARB, orACEI and diuretics


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AKI Superimposed on CKD

Dehydration

BP too low

Obstruction Contrast dye

DrugsNephrotoxic or allergic or hemodynamic

NSAID (including Cox-2 inhibitors)

ACEI / ARB


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Lvolution de la nphropathie est

habituellement associe au dclin progressif

du taux de filtration glomrulaire.

Deces prin - ESRD 59-66% (DZ 1 + DKD)

- BCV 15-25%


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Supravietuirea in HD DP Tx

la 1 an 75% 75% >90%

la 3 ani 50% 85; 68%la 10ani


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Posttransplant evolution

Diabetic glomerulosclerosis recurs in renal allografts from2 to 10 years after transplantation. The earliest and mostfrequent change is arteriolar hyalinosis. Less than 10% ofkidneys develop overt nodular sclerosis.

In patients with type 1 DM, simultaneous pancreatictransplantation can protect against recurrent diabeticnephropathy.

In patients with type 1 DM, pancreas transplantation canreverse the pathologic lesions of diabetic nephropathy,although reversal requires more than 5 years ofnormoglycemia .

boala diabetica de rinichi

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