Post on 06-Apr-2018
8/3/2019 Boala Diabetica de Rinichi
1/46
Diabetic Nephropathy
8/3/2019 Boala Diabetica de Rinichi
2/46
Definition
A microvascular complication of diabetes
marked by albuminuria and a deterioratingcourse from normal renal function to ESRD.
8/3/2019 Boala Diabetica de Rinichi
3/46
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)
8/3/2019 Boala Diabetica de Rinichi
4/46
Redefinirea DKD
BRC aparuta la un pacient cu DZ
Dg: -macroalbuminurie, indiferent eRFG
-eRFG
8/3/2019 Boala Diabetica de Rinichi
5/46
ESRD Incidence Counts and Rates
by Primary Diagnosis (USRDS, 2006)
Better CKDManagement?
8/3/2019 Boala Diabetica de Rinichi
6/46
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
8/3/2019 Boala Diabetica de Rinichi
7/46
8/3/2019 Boala Diabetica de Rinichi
8/46
8/3/2019 Boala Diabetica de Rinichi
9/46
Pathology
Leziuni specifice
Leziuni nespecifice, dar cu frecventa maimare si evolutie particulara:
- macroangiopatia renala (ATS)
- nefroangioscleroza
- infectii
8/3/2019 Boala Diabetica de Rinichi
10/46
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
8/3/2019 Boala Diabetica de Rinichi
11/46
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
8/3/2019 Boala Diabetica de Rinichi
12/46
Glomerulus = filtering unit
8/3/2019 Boala Diabetica de Rinichi
13/46
8/3/2019 Boala Diabetica de Rinichi
14/46
8/3/2019 Boala Diabetica de Rinichi
15/46
8/3/2019 Boala Diabetica de Rinichi
16/46
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
8/3/2019 Boala Diabetica de Rinichi
17/46
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
8/3/2019 Boala Diabetica de Rinichi
18/46
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
8/3/2019 Boala Diabetica de Rinichi
19/46
Natural History
8/3/2019 Boala Diabetica de Rinichi
20/46
8/3/2019 Boala Diabetica de Rinichi
21/46
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
8/3/2019 Boala Diabetica de Rinichi
22/46
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/8/3/2019 Boala Diabetica de Rinichi
23/46
8/3/2019 Boala Diabetica de Rinichi
24/46
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
8/3/2019 Boala Diabetica de Rinichi
25/46
Interventions to Slow CKD Progression
Strong evidenceBlood pressure control
ACEI / ARBGlucose control in DM
Weaker evidence
Protein restrictionLowering LDL cholesterol
8/3/2019 Boala Diabetica de Rinichi
26/46
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
8/3/2019 Boala Diabetica de Rinichi
27/46
Hypertension control:
Linia I: IEC, BRA, diuretice tiazidice
Linia II: BCC, BB, alfa-blocante
8/3/2019 Boala Diabetica de Rinichi
28/46
8/3/2019 Boala Diabetica de Rinichi
29/46
8/3/2019 Boala Diabetica de Rinichi
30/46
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
8/3/2019 Boala Diabetica de Rinichi
31/46
8/3/2019 Boala Diabetica de Rinichi
32/46
8/3/2019 Boala Diabetica de Rinichi
33/46
8/3/2019 Boala Diabetica de Rinichi
34/46
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.
8/3/2019 Boala Diabetica de Rinichi
35/46
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
8/3/2019 Boala Diabetica de Rinichi
36/46
8/3/2019 Boala Diabetica de Rinichi
37/46
8/3/2019 Boala Diabetica de Rinichi
38/46
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
8/3/2019 Boala Diabetica de Rinichi
39/46
Target dietary protein intake : 0.8 g/kg / day
8/3/2019 Boala Diabetica de Rinichi
40/46
Lowering LDL cholesterol:
- Target LDL-C in diabetes and CKD stages 1-4
should be < 100 mg/dL;
8/3/2019 Boala Diabetica de Rinichi
41/46
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
8/3/2019 Boala Diabetica de Rinichi
42/46
AKI Superimposed on CKD
Dehydration
BP too low
Obstruction Contrast dye
DrugsNephrotoxic or allergic or hemodynamic
NSAID (including Cox-2 inhibitors)
ACEI / ARB
8/3/2019 Boala Diabetica de Rinichi
43/46
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%
8/3/2019 Boala Diabetica de Rinichi
44/46
8/3/2019 Boala Diabetica de Rinichi
45/46
Supravietuirea in HD DP Tx
la 1 an 75% 75% >90%
la 3 ani 50% 85; 68%la 10ani
8/3/2019 Boala Diabetica de Rinichi
46/46
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 .