CHRONIC KIDNEY DISEASE (CKD)
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Transcript of CHRONIC KIDNEY DISEASE (CKD)
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CHRONIC KIDNEY DISEASE (CKD)
ETIOLOGY
PATHOPHYSIOLOGY
CLINIC
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Background
• CKD is a worldwide public health problem
• There is a rising incidence and prevalence of kidney failure with poor outcomes and high costs
• Adverse outcomes of CKD can be prevented or delayed
• Earlier stages od CKD can be detected through lab testing
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CKD is often under-diagnosed and under-treated resulting in
lost opportunities for prevention
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CKD – former definition
• Irreversible, in most cases progresses slowly without visible symptoms until kidneys lose their ability of functioning
• Leads to changes in volume and quality of fluids in human body, also causes an impairment of other organs and systems
• It is diagnosed when persistently 3 months GFR value is < 90 ml/min
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CKD – new definition
1. Kidney damage for > 3 months with or without decreased GFR, as manifest by either:
• Pathological abnormalities, or
• Markers of kidney damage (composition of the blood, urine, imaging tests)
2. GFR < 90 ml/min/1,73 m2 for > 3 months with or without kidney damage
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CKD - etiology
•Primary glomerulonephritis 23,75 %•Diabetic nephropathy 19,8 %•Interstitial nephritis 15,4 % (bacterial and non-bacterial)•Hypertonic Nephropathy 10,2 %•ADPKD 8 %•Systemic disaese 2,64 %•Amyloidosis (secondary) 1,85 %•Urinary tract neoplasms 1,19 %•Myeloma mult. 0,59 %•Gout 0,56 %
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Diabetes:The Most Common Cause of ESRD
Primary Diagnosis for Patients Who Start Dialysis
Diabetes50.1%
Hypertension27%
Glomerulonephritis
13%
Other
10%
United States Renal Data System. Annual data report. 2000.
No. of patientsProjection95% CI
1984 1988 1992 1996 2000 2004 20080
100
200
300
400
500
600
700
r2=99.8%243,524
281,355520,240
No
. o
f d
ialy
sis
pat
ien
ts
(th
ou
san
ds)
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CKD czy ARF- how to differentiate?
• An interview- how long does it last?• Symptoms :
-nocturia, polyuria, polydypsia
-itching
-sexual problems / irregular periods
-bone pains, signs of secondary parathyroiditism• Tolerance of high urea and creatinine concentrations• Previously diagnosed renal impairment • Anaemia• Small kidneys in ultrasonography
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CKD – laboratory evaluation
• Urea / creatinine serum concentration
• Assessment of glomerular filtration – GFR -clearance methods -C-G formula -MDRD formula
Cystatine C
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CKD-evaluation
• creatininecreatinine
- derives from muscles (phosphocreatine)
- concentration dependent on body muscle mass i physical activity
- production varies in the daytime- lower at night
- excretion during glomerular filtration, it is not metabolized in kidney, 15% secretion in proximal tubule
- according to the loss of kidney functioning this secretion increases (if GFR 40-80 ml/min, it is > 50%); and excretion of creatinine in bowels enhances (> 6 mg%)
- tubular secretion is inhibited by Cimetidin, Trimetoprime, Amiloride
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CKD - evaluation
• ureaurea
-end product in metabolism of aminoacids
-concentration dependent on glomerular filtration and reabsorption in proximal tubule (due to sodium and water resorption) = 40% in excesive diuresis i 70% in heart failure and dehydration
- dependent on protein intake, high catabolism, heamorrage from digestive tract, drugs, low sodium level, bilirubin level, liver failure
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Stages of CKD
I stage – kidney damage with normal or high GFR GFR 90ml/min proteinuria
II stage - kidney damage with mild decrease of GFR GFR 89 i GFR > 60 ml/min
III stage – moderate decrease of GFR GFR 59 i GFR > 30 ml/min
IV stage – severe decrease of GFR GFR 29 i GFR 15 ml/min
V kidney failure GFR <15 ml/min dialysis
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0,6
2,6
4,6
6,6
8,6
10,6
12,6
14,6
16,6
120 110 100 90 80 70 60 50 40 30 20 10 0
-100%
-0%
TIME – months? years?
GFR
Pcr
II s. mild
III s. moderate
IV s. severe
KF
I stage
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Pathogenesis
Number of nephrons decreases – a rise in concetration of waste from protein
and purine metabolism, phosphate retention, acidosis, uremia toxins.
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Pathogenesis
Glomerular injury and injury of tubules always coexist in advanced stages of disease giving a reduce in filtration and an impairment of reabsorption – we have a lot of metabolic disturbances (impairment of excretory and regualtory function of kidney).
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Pathogenesis - CKD
Impaired endocrine function: erythropoietin 1,25- dihydroksy D3 prostaglandins natriuretic factor kinins
Impaired metabolic function: diminishion of gluconeogenesis prolonged T 0,5 for insulin
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Hormonal disturbances
Secondary parathyreoiditism Hiperinsulinaemia Lack of erythropoietin Lack of active vitamin D3 Hiperprolactinaemia Excess of endorfines Enhanced secretion of somatothropine, calcitonine, gastrine, glukagon Hipogonadism Hiperleptynaemia
RAA system (renin-angiotensin-aldosterone) ADH, natriuretic factors (BNP, ANP)
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0,6
2,6
4,6
6,6
8,6
10,6
12,6
14,6
16,6
120 110 100 90 80 70 60 50 40 30 20 10 0
-100%
-0%
Time- months? Years?
GFR
Pcr
kidney injury
Impaired urine concentration
Hypertension
Dyslipidaemia
mild CKD
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II stage GFR 60 – 89 ml/min
Often subclinical (may remain asymptomatic)!
Prevalence of symptoms of primary kidney disease
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Stage II GFR 60 – 89 ml/min
Impaired urine concentrationIsostenuriaPolyuria and nocturia
DehydrationFluid intake restriction, fever, vomitus,diarrhoea
Fluid accumulationhyponatremia
Heart failure
Decrease in glomerular filtration
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Stage IIGFR 60 – 89 ml/min
Arterial hypertension
• possible in each kidney disease
• frequency of occuring HA increases with progressive loss of glomerular filtration – stage II - 30 – 50% patients, stage V - 90% patients
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Stage IIGFR 60 – 89 ml/min
Factors contributing to hypertension in kidney diseases
• the type of renal disease• GFR value• sex• age• obesity• metabolic abnormalities of carbohydrates and lipids• excessive supplementation of sodium chloride
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Stage II GFR 60 – 89 ml/min
Factors which take place in pathogenesis of HA in patientswith impaired renal function
• salt and water retention• inadequate activation of renin – angiotensin system• activation of symphatetic system• lack of vasodilatating factors• small activity of NO synthetase (ADMA)• circulating inhibitors of Na, K-ATPase • increase of calcium conc. in cells • increase of ET excretion• hyperleptinaemia
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Arterial Hypertension
Renal impairment
Progression of kidney failure depends on:
• increase of HT (specifically systolic and pulse pressure)• lack of decrase of blood pressure at night (nondippers)
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DYSLIPIDAEMIA
TG; CH(LDL) HDL
CKD, HDCH (LDL); TG
HDL
Prot., Per.D, KTx
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0,6
2,6
4,6
6,6
8,6
10,6
12,6
14,6
16,6
120 110 100 90 80 70 60 50 40 30 20 10 0
-100%
-0%
Time-months? years?
GFR
Pcr
Renal impairment
Arterial hypertension
Dyslipidaemia
II stage mild III stage moderate
Anaemia
Abnormalities in Ca – Pi balance
Impaired urine concentration
Nutrition disturbances
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III stageGFR 30 – 59 ml/min
Anaemia
• appears, when glomerular filtration comes to 25 – 30 ml/min• 85 – 87% patients with GFR< 25 ml/min have Hb < 12 – 13 g/dl, but 25% patients with GFR> 60ml/min have Hb< 12 – 13 g/dl• 85% patients starting dialysis treatment have Hb< 10g/dl
• normochromic, normocytic usually
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III stageGFR 30 – 59 ml/min
Causes of anaemia • shorter time of erythrocytes life uremic toxins impaired resistance, deformities of cells hipersplenism• chronic losses of blood• impairment in erythropoiesis lack of erythropoietin production iron deficit advanced secondary parathyroiditism coexisting inflammation inefficient dose of dialysis• hemodilution
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Patophysiological consequences of anaemia
• impaired transport and utilization of oxygen in tissues• heart hypertrophy• low exercise tolerance, weakness of muscles• deteriorating of CNS function• disturbances in immune system• hormonal disturbances
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Stage IIIGFR 30 – 59 ml/min
Abnormalities in Ca-P metabolism
• occur when GFR falls below 50 ml/min• can cause changes in bone structure – renal osteodystrophy• manifest as secondary pararthyreoiditism PTH is one of very important uremic toxins !• are main factors of cardiovascular complications in kidney failure
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Renal Osteodystrophy
• osteitis fibrosa• osteosklerosis• osteomalacia
2 forms of renal osteodystrophy with high bone turnover with low bone turnover
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Stage IIIGFR 30 – 59 ml/min
Changes of nutrition
• when GFR is about 50 ml/min patient spontaneusly starts to reduce protein and callories intake• metabolism of proteins changes• malnutrition gradually develops loss of adipose tissue loss of muscle mass decrease in concentrations of protein, albumin, prealbumin, transferin
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Protein-Calorie Malnutrition
• is an independent prognostic factor in patients with CKD • is one of the parts of MIA syndrome (Malnutrition, Inflammation, Atherosclerosis)
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0,6
2,6
4,6
6,6
8,6
10,6
12,6
14,6
16,6
120 110 100 90 80 70 60 50 40 30 20 10 0
-100%
-0%
Time – months? years?
GFR
Pcr
Renal injury
Hypertension
Dyslipidaemia
s. II mild
S.III moderate
Anaemia
Disturbances of Ca – Pi balance
Impaired urine concentration
Changes in nutrition
S.IV severe
S.V
Metabolic acidosis
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Stage IVGFR 15 – 29 ml/min
Metabolic acidosis
• is caused by low excretion of hydrogen ions• has varied impact on systems enhances proteolysis and reduces protein synthesis (leads to malnutrition) enhances resistance to insulin changes metabolism of bones – impaires function of osteoblasts, enhances function of osteoclasts, enhances release of PTH enhances production and release of 2-microglobulin enhances hypertrigliceridaemia
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Stage IV GFR 15 – 29 ml/min
Signs – cardiovascular complications
•Left ventricle hypertrophy 85% chorych•Left ventricle systolic insufficiency 16% chorych•Left ventricle concetric hypertrophy 41% chorych•Left ventricle distension 28% chorych•normal echocardiography 16% chorych•IHD (young without DM) 24% chorych (aged with DM) 85% chorych •Arteriosclerosis obliterans in lower extremities (DM 1) 30% chorych (DM 2) 40% chorych
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Stage IVGFR 15 – 29 ml/min
Symptoms and signs• severe anaemia• bad controlled HA• overhydration• lack of appetite, nausea, vomitus, malnutrition• weakness, drowsiness• hyperkaliemia, hypocalcemia, hyperphosphatemia
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Kidney failure GFR < 15 ml/min
SYSTEMIC SYMPTOMS AND SIGNS OF UREMIA +SYSTEMIC COMPLICATIONS OF KIDNEY FAILURE
General symptoms• weakness, fatigue• insomnia• malnutrition, cachexia• changes in diuresis• dehydration, overhydration• itching
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Kidney failure
GFR < 15 ml/min
Cardiovascular system• HA• heart failure• IHD• arrhythmias and heart blocks• pericarditis
Respiratory system• Kussmaul breathing• pleuritis• „uremic lung”
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Kidney failure
GFR < 15 ml/min
Gastrointerstinal tract• nausea, vomitus• anorexia• abdominal pain• gastroenteritis (inflammation of mucosa)• haemorrage from digestive tract
Haematologic disorders • anaemia• thrombopathy• bleeding tendecy
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Kidney failure
GFR < 15 ml/min
Nervous s.• headache• peripheral neuropathy
Psychical State• apathy• depression• deterioration of memory, thinking, association
Motoric s.• pain in bones and joints• pathologic fractures• weakness of muscles, muscles atrophy
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Kidney failure
GFR < 15 ml/min
Genital s.• irregular menstruation• fertility• impotence• low libido
Skin• dryness• pallor• scratches, excoriations• ecchymoses• mousy colour