kidney disease in hypertension and diabetes. diagnosis, treatment. ludmila brunerova ii. dpt of...
TRANSCRIPT
Kidney disease in hypertension and diabetes. Diagnosis, treatment.
Ludmila BrunerovaII. Dpt of Internal Medicine FNKV
and Mediscan Euromedic
Diabetic nephropathy Nephropathy in hypertension
Diabetic nephropathy - definition
nephropathy caused by diabetes (Kimmelstiel Wilson glomerulosclerosis as a microangiopathy disease)
nephropathy as a macroangiopathy disease in diabetes
urinary tract infection in diabetic patients
Kidney disease in diabetes
Diabetic nephropathy (DN)
Non-diabetic nephropathy glomerular primary glomerulonephritis secondary glomerulopahies non-glomerular renovascular disease
chronic TIN (tubulointerstitial nephritis) necrosis of papilla polycystic renal disease reflux nephropathy
Iatrogenic renal impairment (drugs, radiocontrast)
PathophysiologyHyperglycaemia
Glycation endproducts (AGE)
activation of signal transductionPKC, MAP kinase, NF-κB Reactive oxygen
radicals
Vasoactive systems
Hemodynamicchanges
Growth factorsCell cycle changes
Tubulointerstitial fibrosisProteinuria
GlomerulosclerosisRenal failure
Epidemiology
4-8% diabetic patients type 1 diabetes mellitus proteinuria: 25-45% type 1 diabetic patients microalbuminuria: 20-30% type 1 diabetic
patients maximal prevalence – after 15 years of
diabetes duration small risk of development of diabetic
nephropathy after 25 years of diabetes duration
type 2 diabetes mellitus: prevalence 25% after 15 years of
diabetes duration ( Pima Indians – 50%)
year incremental in incidence of microalbuminuria 15-25% in bad control of risk factors
Epidemiology of chronic renal failure in diabetic
patients good evidence since 1990 diabetic nephropathy
has been one of the three most common causes of renal failure
prevalence of diabetics in dialysis therapy 35%, mortality 29% (versus 20% in nondiabetic patients)
Phases of diabetic nephropathy
Phase 1: hyperfiltration-hypertrofic …. functional changes hyperfiltration ( GF o 20-40%) hyperperfusion renal hypertrophy asymptomatic
Phase 2: latent
…. normalization of functional changes, onset of morphologic changes
after 2-4 years of diabetes duration GF or normal, albuminuria not
present thickening of basal membrane mesangial thickening asymptomatic
Phase 3: incipient diabetic nephropathy
…. progression of morphologic changes, microalbuminuria, normal function
after 6-15 years of diabetes duration GF normal, typical morphologic changes microalbuminuria (30-300mg/24 hours) in 20% DM1, 80% progress to phase 4, marker of
nephropathy progression in 40% DM2, only 20-40% progress to phase 4,
marker of endothelium dysfunction (cardiovascular morbidity and mortality)
asymptomatic, or hypertension in DM2
Phase 4: manifest diabetic nephropathy
…. proteinuria, renal insufficiency after 10-20 years of diabetes duration proteinuria > 300mg/24 hours, 15-40%
incremental per year GF in 0,17 ml/s/year… renal
insufficiency hypertension, nephrotic syndrome,
progression of other diabetic complications, complications of renal insufficiency
Phase 5: chronic renal failure, need for RRT
> 20 years of diabetes duration > 7 years of proteinuria duration high mortality (cardiovascular
complications) complications of renal failure
Lab tests
diagnosis of DN = persistent albuminuria > 30mg/24 hours (2/3 measurements in 6 months), in presence of diabetes, after exclusion of other renal disease
urine ch+s examination of proteinuria examination of renal function Ultrasound of kidneys
Proteinuria physiological 15-25mg/24 hours mikroalbuminuria: 30-300mg/24
hours (20-200ug/min), Transient 30-100mg/24 hours resp. 20-
70ug/min persistent 100-300mg/24 hours resp 70-
200ug/min albuminuria: > 300mg/24 hours (resp.
200ug/min)~0,5g/day – >3,5g/24 hours – nephrotic proteinuria
Evaluation of renal function
S-crea GFR MDRD Cystatin C
S-crea (umol/l)
100
500
900
GFR (ml/s)0,2 1,0 2,0
Principles of diagnosis – I.
Diagnosis clinical… (ADA, 2003) Progressing proteinuria in patients
with longeterm history of type 1 DM > 10 let
Microalbuminuria preceded With diabetic retinopathy Without microscopic hematuria With normal ultrasound finding
Diagnostic problems in type 2 DM Proteinuria can be present in time of
diagnosis Coincidence with retinopathy is less
frequent in type 2 DM Microscopic hematuria in progressed
stages of diabetic nephropathy Relatively frequent concomittance with
non diabetic nephropathy
Principles of diagnosis- II.
Dif dg
Typical clinical-laboratory finding for DN
Long history of diabetes Diabetic retinopathy present Mikroalbuminuria (longterm) proteinuria
nephrotic proteinuria renal insufficiency
Renal biopsy not indicated
Dif dg Typical finding in renovascular
disease Elderly, sclerotic With renal insufficiency (s-crea 130-
200umol/l) Small proteinuria (<1-2g/24 hours) Hypertension Ultrasound – asymetry, bilateral small
kidneys, reduced cortex Biopsy not indicated
Doppler, MRA, DSA
Dif dg
Atypic finding in patient with DM Rapid progression of proteinuria and renal
insufficiency Short history of diabetes, no retiopathy Glomerular erythrocyturia Discrepancy – ultrasonography vs clinical Chronic renal insufficiency without proteinuria
and/or retinopathy
Renal biopsy indicated to exclude glomerulonephritis
Dif dg
„inflammation“ sediment
With positive cultivation – urinary tract infection, asymptomatic bakteriuria
With sterile pyuria – TBC, necrosis of renal papilla
Metabolic control – diabetes,Lipids, obesity
Glycaemic control (IIT, event. gliquidon, low protein diet), weight reduction
smoking stop smoking
hypertension
albuminuria
Optimal BP control with target BP < 130/80mmHg Renoprotective: ACEi sartans
Urinary tract infection Early treatment
angiotenzinogen
angiotenzin I.
ACE
renin
chymase
bradykinin
NO, PG
vasodilatationvasoconctriction,atherosclerosisinflammation
AT1R AT2R
angiotenzin II.
Inacive peptides
AT1R
?
Cascade after ACEi
Cascade after sartans
Cascade after direct inhibition of renin
Case 1
Man, 42 years Type 1 diabetes for 23 years, CSII Diabetic retinopathy Microalbuminuria first evidenced 8
years ago Smoking, no other treatment Now coming for hypertension and
oedema of legs
Case 1
Lab: urea 18mmol/l, s-crea 198umol/l Na 145, K 5,9 Ca 2,1 P 1,9 albumin 22g/l, glycaemia 13mmol/l Cholesterol 6,4 mmol/l, LDL 4,4 HDL
0,9 Tg 1,7 Urine: protein +2, glucose +2 GF 0,75ml/s, proteinuria 8,6g/day
Case 1
What is patient´s problem? How would you treat the patients?
Case 2
Type 2 diabetic woman 44 years, obese Diabetes for 2 years, good control on
diet, no other diseases, no medication In preventive check found hypertension
190/100, urea 14mmol/l, s-crea 239umol/l
Urine: protein + 1, erythrocyte 85, glomerular origin, proteinuria 1,8g/day
Ultrasound: bilateral kidney 87mm, cortex 9mm
Case 2
Does the patient have diabetic nephropathy?
Why? What other examination would you
recommend? How would you treat the patient?
Conclusion I.
Diabetic nephropathy – microvascular complication connected to poor glycaemic control
… leading cause for need of dialysis Prevention and therapy –
nephroprotective strategies: BP control (ACEi, sartans), glycaemic control, lipid control
Kidney disease in hypertension
kidney and regulation of blood pressure
exretion of salt and water (volume of extracelullar fluid)
endocrine function – secretion of vasoconstrictors (RAS) and vasodilatators (Pg, calicrein, kinins)
perception of osmolarity and volume (pressure)
Kidneys hypertension
role of kidneys in primary hypertension (unability to excrete salt load)
kidney disease as cause of secondary hypertension (renoparenchymal, renovascular)
hypertension causes renal damage hypertension is the leading factor of
progression of kidney disease
kidney disease
GF
natrium excretion
ECF
hypertension
intrarenal ischaemia
RAAS SAS
damage of medulla
Pg, kinins
Hypertension-induced renal dysfunction
hypertension nephropathy – longterm hypertension causes kidney damage
ischaemic nephropathy - atherosclerotic changes in macrovessels (altogether with diabetes, hyperlipidaemia).. renovascular hypertension
vascular nephropathy (nephrosclerosis) – affection of smaller renal vessel causes kidney dysfunction
renovascular kidney disease – vascular nephrosclerosis + ischemic nephropathy
Epidemiology of hypertension-induced
nehropathy (HIN) 3rd after ischaemic heart disease
and stroke RR of kidney dysfunction – 12,5x
Pathology of HIN
benign nephrosclerosis stenosis of renal arteries malign nephrosclerosis
Benign nephrosclerosis
in autopsy: 16-18% men and 15-27% women
clinical follow up: 15% of patients with hypertension
pathology: thickening of arterial wall, hyalinosis, infiltration of interstitium, interstitial atrophy and fibrosis
…smaller kidneys
systemic hypertension
vasoconstriction of afferent artery
hypoperfusion
GF
impairment of renal vessel autoregulation
dilatation of afferent artery
hyperperfusion, hyperfiltration
proteins to mesangiumand Bowman´s capsula
RAS
tubulointerstitial fibrosis and dysfunction
renal failure
Clinical symptoms and lab test
asymptomatic nycturia (tubuluinsterstitial changes
in concetration) early lab findings: microalbuminuria
(5-40%), small proteinuria (<1h/day), hyperurikemia, normal renal function
late lab findings: renal dysfunction, S-crea, chronic renal failure (3%)
Diagnosis and dif dg
longterm history of hypertension exclusion of other renal diasease hypertonic eye changes small proteinuria dif dg: ischaemic nephropathy
(bilateral renal arterial stenosis), cholesterol microembolization
Treatment
blood pressure control – 130/80 (125/75)
diet, salt intake ACE inhibitors, sartans, verapamil
+ other antihypertensive drugs intensive treatment of other risk
factors (lipids, glycemia)
Malign nephrosclerosis
rare <1% of patients with hypertension
(severe) pathogenesis – failure of renal
vessel autoregulation pathology – proliferation
endarteritis, fibrinoid necrosis of afferent arteries and capilaries – necrotic glomerulonephritis
Clinical findings and lab tests
extreme hypertension
headache, encephalopathy, coma
neuroretinopathy left heart failure
proteinuria (nephrotic)
erythrocyturia cylinder progressing renal
insufficiency
Therapy
therapy of emergent hypertension ICU i.v. antihypertensives (nitrates,
urapidil, labetalol…) hemodialysis mortality – 30%
Stenosis of renal artery/ies
Hypertension or CKD due to hemodynamicaly significant (>75%) renal arterial stenosis (RAS)… 3%
Renovascular diseases – renal arterial stenosis with/without hypertension
Ischaemic nephropathy – renal dysfunction due to renal ischaemia (bilateral RAS)
Atherosclerosis (high age, 80%) Fibromuscular dysplasia (younger
women, 25%) Embole, aneurysm, dissection,
malformation Arteritis Extramural pressure (tumors, fibrosis,
uretheral obstruction, cysts…) …. RAAS activation
Renal arterial stenosis - causes
sudden onset, worsening + retinopathy + negative family history + smoking + vascular history (IHD, PAD) + renal function impairment after
ACEi + abdominal murmur
Renovascular hypertension- clinical
Lab: hypokalemia, PRA, aldosterone (secondary hyperaldosteronism), proteinuria, S-crea
Ultrasound: renal asymetry (10-15mm), cave bilateral stenosis, IR
Dynamic renal scintigraphy with enalaprilate
MRA DSA
Renal arterial stenosis - diagnosis
Aims: hypertension control preservation of renal function PTA: fibromuscular dysplasia and
hypertension/renal dysfunction, others? Surgery (aortorenal bypass): aneurysm,
restenosis Pharmacological: slow titration of
ACEi/AT1 (Cave k.i. bilateral stenosis), diuretics, other antihypertensives
Renal arterial stenosis - therapy
Ischaemic nephropathy
GF due to hemodynamic significant obstruction of blood flow in both renal arteries or in renal artery of solitary kidney or renal failure due to total kidney aperfusion
atherosclerotic renovascular disease atheroembolic kidney disease
Epidemiology
15-16% progress to ESRD (3rd after diabetic nephropathy and chronic glomerulonephritis)
mortality in dialysis (average survival 27 months)
Atherosclerotic renovascular disease
(ARD) bilateral renal arterial stenosis –
25-30% patients with renovascular disease
more frequent in diabetics after Tx – 3-10%
Forms of ARD
Acute renal failure or Rapidly progressing renal insufficiency
sudden occlusion of stenotic renal arteries with thrombosis, or embolization
trias: nephralgia + hypertension + hematuria (+ leucocytosis, subfebrile)
poststenotic perfusion after ACEi or sartans
in 2 weeks after treatment, ARF in 6-10% patients with significant stenosis
chronic renal insufficiency and failure
chronic kidney ischaemia due to hypoperfusion in significant renal arterial atherosclerotic stenosis
asymptomatic…. left heart failure (RAS) loss of renal function - GF
4ml/min/year collateral circulation
Forms of ARD
Diagnosis and dif dg
progression of renal insufficiency of unknown origin in elderly hypertonic patiens with atherosclerotic history (stroke, MI…)
rapid and significant impairment of renal function after antihypertensives (not only ACEi, sartans)
dif dg: acute tubular necrosis, other nehropathies connected with hypertension
Hypertension-induced nephropathy
Ischaemic nephropathy
age 40-60 > 60
race Afroamerican Caucasian
cause
hypertension atherosclerosis
mech perfusion change in HT
hypoperfusion
goal lowering of BP stenosis correction
surviv
relatively good poor
Examination
ultrasound + doppler dynamic scintigraphy (+
enelaprilate) MRA of renal arteries CTA of renal arteries DSA of renal arteries
Therapy
revascularization - reperfusion! bypass PTA conservative treatment – in k.i. of
invasive BP control, intervention of risk
factors ASA
Prognosis and prevention
good prognosis in mild renal insufficiency (s-crea< 130 umol/l)
stabilization of renal function in s-crea 130-265 umol/l
poor outcomes in severe renal dysfunction (s-crea>265 umol/l) – 50% progress to ESRD
effect of revascularization on hypertension – mostly poor, preventive in pulmonary oedema
prevention – general prevention of atherosclerosis
Atheroembolic kidney disease
embolization of parts (cholesterol) of atheromatic plaque to peripheral circulation (arteries 150-250 um) – induction of inflammation
spontaneous (aneurysm of aorta, anticoagulation therapy)
after intervention (DSA, PTA) 0,6-6%
Acute cholesterol microembolization suddan lumbal pain, subfebrile hypertension, oliguria proteinuria, hematuria + abdominal (vomitus, ileus, GIT bleeding,
spleen infarction) + nervous (paresthesia, paresis, amaurosis,
TIA) + skin (cyanosis, livedo, ulceration of
peripheral parts of limbs)
Atheroembolic kidney disease
Acute cholesterol microembolization
diagnosis – difficult coincidence with intervention impairment of renal function eosinophilic leucocyturia biopsy (microembolization) dif dg: other causes of ARI therapy: nephroprotection (hydration,
blood pressure control), poor outcome
Chronic cholesterol microembolization successive embolization from exulcerated
atherosclerotic plaques in elderly sclerotic patients
successive development and progression of renal dysfunction
lab: nonsignificant (proteinuria in FSGS) ultrasound: aneurysm of abdominal aorta
Atheroembolic kidney disease
Case III.
76 year-old woman History of hypertension (for 40years),
type 2 diabetes on diet, MI (2x), stroke 1x Multicombination antihypertensive
therapy, statins BP 150/95mm Hg S-crea 140umol/l, urea 17mmol/l Urine: protein +1, no erythrocytes,
proteinuria 0,9g/day Ultrasound: bilateral kidney 80mm,
cortex 7mm
Case III.
What nephropathy does the patient have?
What else could she have? What examination would you
recommend? How would you treat the patient?
Case IV.
Woman 40 years Sudden unset of severe hypertension –
190/100, normal urea and creatinin, normal urine
Therapy with perindopril in dose 10mg started, Ca blocker (amlodipin 10mg) and BB (metoprolol 100mg) added
After 2 months – BP 110/60, urea 16mmol/l, creatinin 349umol/l
Ultrasonography: asymetry of kidneys (R 85mm, L 108mm)
Case IV.
What type of hypertension did the patient obviously had?
What was wrong in the diagnostic process?
What was wrong in the therapy? What examination would you
recommend? What treatment?
Conclusion II.
Relation between hypertension and renal function reciprocal
Untreated hypertension leads to renal damage
Kidney diseases lead to hypertension Prevention and therapy – blood pressure
control to target Inhibitors of RAS, revascularization if
possible
Conclusion
Diabetes is the leading cause for dialysis treatment in developed countries
Reciprocal relationship between hypertension and renal disease
Untreated hypertension causes renal damage… and failure