CHRONIC KIDNEY DISEASE (CKD)

1. CHRONIC KIDNEY DISEASE (CKD) ETIOLOGY PATHOPHYSIOLOGY CLINIC

2. 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

3. CKD is often under-diagnosed and under-treated resulting in lost opportunities for prevention

4. 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

5. 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

6. 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 %

7. Diabetes Hypertension 50.1% 27% Diabetes:The Most Common Cause of ESRD Primary Diagnosis for Patients Who Start Dialysis Glomerulonephritis Other No. of patients 10% 13% 700 Projection 95% CI 600 500 400 No. of dialysis patients (thousands) 520,240 300 281,355 200 243,524 100 r2=99.8% 0 1984 1988 1992 1996 2004 2000 2008 United States Renal Data System. Annual data report. 2000.

8. 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

9. CKD – laboratory evaluation • Urea / creatinine serum concentration • Assessment of glomerular filtration – GFR -clearance methods -C-G formula -MDRD formula Cystatine C

10. CKD-evaluation • creatinine - 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

11. CKD - evaluation • urea -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

12. 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

13. Pcr -0% KF IV s. severe III s. moderate II s. mild I stage -100% GFR TIME – months? years?

14. Pathogenesis • Number of nephrons decreases – a rise in concetration of waste from protein and purine metabolism, phosphate retention, acidosis, uremia toxins.

15. 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).

16. 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

17. 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)

18. Pcr -0% kidney injury mild CKD Dyslipidaemia Hypertension Impaired urine concentration -100% GFR Time- months? Years?

19. II stage GFR 60 – 89 ml/min Often subclinical (may remain asymptomatic)! Prevalence of symptoms of primary kidney disease

20. Stage II GFR 60 – 89 ml/min Impaired urine concentration  Isostenuria  Polyuria and nocturia Fluid accumulation hyponatremia Dehydration Fluid intake restriction, fever, vomitus, diarrhoea Heart failure Decrease in glomerular filtration

21. 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

22. 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

23. Stage II GFR 60 – 89 ml/min Factors which take place in pathogenesis of HA in patients with 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

24. 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)

25. DYSLIPIDAEMIA TG; CH(LDL) HDL CH (LDL); TG HDL CKD, HD Prot., Per.D, KTx

26. Pcr -0% Renal impairment III stage moderate II stage mild Nutrition disturbances Abnormalities in Ca – Pi balance Anaemia Dyslipidaemia Arterial hypertension Impaired urine concentration -100% GFR Time-months? years?

27. 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

28. 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

29. 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

30. 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

31. Renal Osteodystrophy • • osteitis fibrosa • • osteosklerosis • • osteomalacia • 2 forms of renal osteodystrophy • with high bone turnover • with low bone turnover

32. 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

33. Protein-Calorie Malnutrition • is an independent prognostic factor in patients with CKD • is one of the parts of MIA syndrome (Malnutrition, Inflammation, Atherosclerosis)

34. Pcr -0% S.V S.IV severe Renal injury S.III moderate s. II mild Metabolic acidosis Changes in nutrition Disturbances of Ca – Pi balance Anaemia Dyslipidaemia Hypertension Impaired urine concentration -100% GFR Time – months? years?

35. 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

36. 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

37. 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

38. 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

39. Kidney failure GFR < 15 ml/min Cardiovascular system • HA • heart failure • IHD • arrhythmias and heart blocks • pericarditis Respiratory system • Kussmaul breathing • pleuritis • „uremic lung”

40. 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

41. 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

42. Kidney failure GFR < 15 ml/min Genital s. • irregular menstruation • fertility • impotence • low libido Skin • dryness • pallor • scratches, excoriations • ecchymoses • mousy colour