Complications of diabetes –
diabetic nephropathy
Jan Svojanovský
II.interní klinika FN USA a LF MU
2
- chronic disease causing high mortality, invalidity
and morbidity all over the world
- whole world: cca 170 mil. (2000)  366 mil.
(2030)
- prevalence in Czech rep.: cca 8 %
 : DM type 1 7,2%
DM type 2 91,4 %
Diabetes mellitus
3
4
- complications:
A/ macroangiopathic (atherosclerosis)
– Ischemic heat disease
- Chronic lower
limb ischemia
- Cerebrovascular disease
Diabetes mellitus
5
- complications:
B/ microangiopathic
- retinopathy
(60%)
- nephropathy
(25-45%)
- neuropathy (50%)
Diabetes mellitus
Diabetic kidney disease - DKD
6
• clinical syndrom caused by specific morphologic
and functional changes of kidneys in patients with
diabetes mellitus typu 1 or 2
• major clinical sings: persistent proteinuria
hypertension
decreasing renal function
Epidemiology of DKD in CZ
 2015:
858 000. ptx with DM
(91.7% type 2)
 number of complications
248 000
7
Ročenka ÚZIS 2015
Epidemiology of DKD
 DM type 1
during 10 years onset of DKD in 4% ptx
25 years……..……………. 25% ptx
 DM type 2
during 5 years onset of DKD in 10% ptx
20 years……………..…………30% ptx
8
Morphologic characteristics
of DKD
 thickening of glomerular basal
membrane
 accumulation od mesangial
matrix → expansion of
mesangial space in glomerulus
 oppression of glumerular
capillaries → loss of filtration
surface - diabetic nodular
intercapillary
glomerulosclerosis
(syndrom Kimmelstiel-Wilson)
9
Pathophysiology of DKD
 As a result of interaction of both metabolic and
hemodynamic factors we can see structural
changes of kidney tissue
 metabolic factors:
persistent hyperglycaemia, oxidative stress,
glykosylation of proteins, polyol pathway of glukosa
metabolism…
 hemodynamic factors:
systemic and intraglomerular hypertension → lokal
produktion of cytokines and growth factors (PKC,
TGFβ…)
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2. metabolic factors
1. hemodynamic factors
5. abnormalities
of cell growth
and creation of
ECM
4. alteration of signal
functions
Structural changes
in kidney tissue
Pathophysiology of DKD
6. alteration of podocytes
3. oxidative stress
Diagnosis of chronic kidney
disease/diabetic kidney
disease
(CKD/DKD)
12
GFR categories (KDIGO 2012)
Definition of chronic kidney disease
- criteria (KDIGO 2012)
Metabolic and clinical complications of
CKD/DKD
 appearing early, even from CKD3 (GFR <
60ml/min)
 impairment of Ca-P-vitD metabolism –
secondary hyperparathyreoidism , renal bone
disease = CKD- MBD
 secondary anemia (and its consequences)
 metabolic acidosis (and its consequences)
 uremic symptoms: nauzea, vomiting, diarhoea,
pruritus
Therapeutic approaches at
CKD/DKD
 treatment of anemie – iron,
erytropoetin
 treatment of renal osteopathy (CKDMBD)
– vit.D, Ca supplement., P-binders
 treatment of hypertension
 diet restrictions
Diet restriction in CKD
 creatinin 150-250umol/l:
- 0.8g protein/kg/day
- energy intake 140-150kJ/kg/day
- phosphate intake 1-1,2g/day
- low sodium intake if hypertensis or oedema are present
- fluid intake according to diuresis
Diet restrictions in CKD
 creatinin 250-600umol/l:
- 0.6g of protein/kg body weight/day
- energy intake150-160kJ/kg/day
- phosphate intake 0,6-0,8g/day
- calcium intake 1,5g/day
- sodium intake 80-100mmol
- fluid intake according to duresis
- ketoanalogs of essential aminoacids to improve
anabolism (Ketosteril)
Non-diabetic nephropaties of diabetic
patients
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a/ glomerular – primary and secondary GN
b) non-glomerular
- renovascular disease (RVD) stenosis of a.renalis,
hypertensive nefrosclerosis
- tubulointersticial nephritis
- others
c) iatrogenic damage to kidney nephrotoxic
agents
 radiocontrast media
 drugs (non-steroidal antiinflamatory
drugs, antibiotics –aminoglykosids)
Renal biopsy
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Diabetic ptx – Czech registry of renal
biopsies 1999-2001
• Number of RB: 1946
• Number of diabetics 196 (10,1%)
• Dg according to RB:
- KSW 80 (40,8 %)
- other GN 95 (48,5 %)
(IgAN 17.5 %, membranous GN 11%,
nephrosclerosis 11%, vasculitic 9%)
- non-diagnostic RB21 (10,7 %)
30
Rychlík et al, NDT,2004
Therapeutic options to influence the
progression of diabetic kidney
disease
38
Basic therapeutic approaches in
treatment of diabetic patient with
nephropathy in 2018
• blockade of renin-angiotensin system (RAS)
• proper compensation of arterial hypertension
(blood pressure below 130/80)
• metabolic compensation
- normoglycemia
- normolipidemia
• other regime measures (protein restriction…)
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Mechanism of ACEI on
intraglomerular hemodynamics
Effekt of RASblockade
• antihypertensive
• antiproteinuric
• renoprotective
Blokátory RAS – klinické použití
IR
ACEi ACEi
ARB
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New antidiabetic drugs and
impact on DKD
47
Kim Y. et al, KJIM 2017;32, 11-25
• GLP-1 agonists
- sitagliptin,
- vildagliptin
- saxagliptin
• DPP4 inhibitors
- exenatid
- liraglutid
Effekt: ↓ albuminuria
↓ production of TGFβ
(↓ inflamation and fibrosis)
New antidiabetic drugs and
impact on DKD
 SGLT2 inhbitors (gliflozins)
- dapagliflozin
- empagliflozin
- canagliflozin
Effekt:
↓ albuminuria
↓ hyperfiltration
↓ glomerular
hypertension
48Kim Y. et al, KJIM 2017;32, 11-25
Renal replacement therapies (RRT)
 hemoelimination techniques: hemodialysis
hemodiafiltration
 peritoneal dialysis: continuous ambulatory PD
automatic PD (cycler-assisted)
 kidney transplant: cadaveric (deceased) donor
living donor
RRT - comparison
excretor.
Function
metabol./
endocr.
availability
1. HEMOELIMINATION
1.1. hemodialysis
1.2. hemofiltration
1.3. hemodiafiltration
+ – immediate
2. PERITONEAL DIALYSIS
2.1. CAPD
2.2. APD – cycler assisted
+ – weeks
3. KIDNEY TRANSPLANT + +
months-
years
RRT – algorithm
Hemodialysis Peritoneal dialysis
Cadaveric donor kidney
transplant
Chronic
renal failure
Living donor kidney
transplant
Principle of hemodialysis
Vascular accesses for HD
Osnova přednášky
 diabetické onemocnění ledvin (DKD) - úvod
 epidemiologie, morfologie a patofyziologie DKD
 diagnostika DKD
 nediabetické nefropatie u diabetiků
 základní principy léčby DKD
 nové možnosti léčby DKD
 závěr
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Peritoneal dialysis
 blood is purified by repeated exchanges
(influx/outflux) of peritoneal solution by
catheter, which is placed into abdomen
cavity
 peritoneum acts like semi-permeable
membrane
 efficiency is equal to HD
Advantages of PD
 continuous way of blood purification
 gradual removal of fluid, no fluctuations of blood
pressure and thus longer conservation of residual
diuresis
 usually no restriction in fluid intake (according to
residual diuresis)
 no blood losses a no need for systemic
anticoagulation
 treatment at home
Disadvantages of PD
 gradual fibrosis of peritoneal membrane – loss of
dialysis ability
 permanent risk of infection – acute peritonitis
 esthetic point of view – peritonel catheter in
abdomen
 bathing restrictions (shower and salty water OK,
bath tub NO)
 composition of peritoneal fluid is not metabolic
inert (content of glukosa)
 need for permanent life partner
Kidney transplant
 advantages: replace of both metabolic and
endocrine functions of kidney, return to“normal
life“, 2x longer survival time versus HD/PD, cost
effectiveness
 disadvantages: limited availability – necessity to
find suitable couple donor x recipient, necessity to
use maintenance imunosupressive drug (higher risk
of infections and tumours)
Kontraindikace TL
 Nesouhlas s TL
 Maligní a aktivní zánětlivá onemocnění
 Drogová závislost včetně alkoholizmu
 Nespolupracující nemocný
 AIDS/HIV pozitivita ??
 Periferní gangréna
 Pokročilé onemocn.nerenálního původu
 Vícečetné stenózy tepen DK neřešitelné
 BMI > 35
Methods of kidney transplantation
 living donorTx (in CZ 13%, in Western
Europe and USA up to 50%)
 cadaveric donorTx (in CZ 87% of Tx)
 donors: people with brain death (after
craniotrauma, spontaneous brain hemorrhage) or
non-hearbeating donors
 in CZ system of „presumed consent“
Placement of kidney graft
Results of kidney Tx
 10-years survival
 recipients: 70-80 %
 grafts: 50-70 %
 both is by 15-20 % better in living donorTx
 Most common cause of graft failure are death of
recipient with functioning graft and chronic
rejection
 Most common cause of death of recipient are
cardiovascular complicantions (>40%), infections a
malignancy
Thanks for attention
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