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ACUTE KIDNEY INJURY (AKI)
Rapid decline in GFR, perturbation of EC fluid volume and
electrolyte and acid-base homeostasis
KDIGO 2012 definition of AKI s-creatinine increase by ≥26 µmol/l
within 48 hours, or
>1,5 times from baseline within prior 7 days
Urine output
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Prerenal AKI (~ 55%) - renal hypoperfusion
Hypovolemia (dehydration, hemorrhage, renal and GI fluid
losses,
sequestration to extravascular space), Low cardiac output
Impaired renal autoregulation (ACE inhibitors, COX
inhibitors)
Intrinsic renal AKI (~ 40%)
Acute tubular necrosis (ischemia, aminoglycosides, chemotherapy,
radiocontrast media, rhabdomyolysis, hemolysis, HELLP, urates)
Interstitial nephritis: allergic (cephalosporins, NSAIDs),
infection
Glomerulopathies glomerulonephritides,
hemolytic uremic sy HUS,
thrombotic thrombocytopenic purpura TTP, disseminated
intravascular coagulation DIC,
eclampsia
Postrenal AKI (~ 5%) - urinary tract obstruction
(calculi, cancer, blood clot, neurogenic urinary bladder in
DM-2)
Pathophysiology of AKI Initiation phase - RBF, obstruction of
tubules, backleak of
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glomerular filtrate, outer medulla
Maintenance phase -, intrarenal vasoconstriction
(endothelin,
angiotensin II, thromboxan, nitric oxide, prostaglandins),
congestion of medulla, urine output
Recovery phase - polyuria
Risk factors: hypovolemia, preexisting nephropathy, elderly
patients,
diabetic patients.
Clinical picture Initiation phase - 2-6 days, urine output,
symptoms: weakness,
nausea, vomiting, headache, edema, myalgia, dyspnea Oligoanuria
- oliguria
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Hydro-mineral balance:
- water loss by perspiration and expiration 850-1000 ml/24 h
- increased water loss in fever - in catabolic state 500 ml of
metabolic water is generated
Maintaining of appropriate hydration (CVP): Water intake/24 h =
urine + GIT losses + 400 ml
Conservative measures: Low-protein diet 0.6 g/kg/day
Furosemide i.v.
Metabolic acidosis correction Treatment of hyperkalemia
Preventive measures: Optimization of CV function and
intravascular volume
Contrast media – non-ionic, low-osmolar, 1/2 saline infusion
Aminoglycosides, cefalosporins, cyclosporin – serum levels!
Purification methods:
haemodialysis, peritoneal dialysis, hemoperfusion
CHRONIC KIDNEY DISEASE (CKD)
CKD classification, 2012 KDIGO Guideline
Chronic kidney disease criteria (duration more than 3
months)
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Markers of kidney injury: 1. albuminuria >30 mg/24 h, urinary
albumin/creatinine ratio
ACR>3 mg/mmol, 2. abnormalities in urinary sediment 3.
abnormal serum concentrations of electrolytes in renal tubular
disorders 4. pathological histologic findings 5. abnormal renal
structure by imaging techniques (USG, CT,
MRI, radioisotope methods) 6. kidney transplantation
and/or
Decreased glomerular filtration rate eGFR
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IC Na - overhydration of cells- total body H2O - s-Na
Impaired metabolism of Na and H2O - risk of ECV depletion
Potassium homeostasis - s-K, if GFR
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Parathormone enhances Ca resorption in distal nephrone and
mobilizes Ca from bones. Secondary hyperparathyroidism
Renal osteopathy: osteomalacia (vitamin D, calcium deficit),
osteitis
fibrosa cystica (PTH on bone), adynamic osteopathy
TMV classification: bone turnover, mineralisation, volume
Neurologic, psychiatric abnormalities
- peripheral neuropathy (sensoric, motoric),myopathy, spasms,
restless legs, encephalopathy, cognitive functions, depression
- dialysis disequilibrium
Gastrointestinal foetor, delayed emptying of stomach,
vomitus,
peptic ulcer, hepatitis B, C, diarrhea
Endocrine - estrogen, amenorhea, testosterone, cortisol, T3,
growth hormone (children)
Skin – brown pigment, hematoma, pruritus, calcif. necrosis
CONSERVATIVE THERAPY
Goal: to slow down a progression of chronic kidney disease
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Low-protein diet
decreases the formation of nitrogen waste products and inorganic
ions, attenuates uremic symptoms, metabolic acidosis,
hyperphosphatemia and hyperkalemia Protein intake:
at risk of CKD – not to exceed 1,3 g protein/kg/day CKD stages 2
and 3 – 0,8-1 g protein/kg/day
CKD stages 4 and 5 (GFR30)– below 0,8 g protein/kg/day
Hemodialysis 1,2 g/kg/day, CAPD 1,3 g/kg/day, High biological
value proteins – 50-75%
Energy intake 150 kJ (35 kcal)/kg
ketoanalogues of essencial aminoacids, folate, vitamin C, B6
Antihypertensive treatment
Goal: BP250 mol/l),
angiotensin II receptor blockers (ARB),
calcium channel blockers (NDHP, DHP), beta-blockers, centrally
acting, diuretics (limited effect)
Renal anemia Goal: Hb up to 115 g/l
Check: s-Fe, s-transferrin (t. saturation), s-ferritin!
Therapy: obtain adequate iron stores, administer Fe p.o., if
insufficient intestinal absorption i.v. (anaphylaxis is rare)
ESA (erythropoiesis stimulating agents): Recombinant human EPO
100-150 IU/kg/week s.c., or i.v.
EPO types: alfa, beta, delta (2 až 3-times/week)
every 2 to 4 weeks: darbepoetin,
methoxy-polyetylen-glykol-epoetin-beta
Metabolic acidosis
Correction, if HCO3
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Renal bone disease (osteodystrophy)
Goal: s-P2.2 mmol/l, Ca x P
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HEMODIALYSIS
Principle: diffusion of molecules (anorganic ions, small
molecules –
urea, creatinine, middle molecules, large molecules – beta2-
microglobuline) from blood across artificial semipermeable
membrane (high-flux membrane) into dialysate (isoionic,
bicarbonate), sodium levels modeling
Indications: ARF, CHRF (s-creatinine 500-600 mol/l),
hyperkalemia>7.0 mmol/l, severe metabolic acidosis
Contraindications: arterial hypotension, acute bleeding
(start
heparin-free HD)
Vascular access - 3-way caval catheter, a-v fistula
(forearm)
Heparin during HD, HD duration 4 hours 3-times a week
Ultrafiltration removes excessive fluid from a body
Complications: arterial hypotension, bleeding (heparinization),
hyperpyrexia, dialysis disequilibrium
Hemofiltration, hemodiafiltration, hemoperfusion
PERITONEAL DIALYSIS
Principle: diffusion of molecules from blood across
peritoneal
capillary wall to dialysate, which is instilled to peritoneal
cavity via catheter (one exchange equals 2 litres)
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Peritoneal fluid: Na, Ca, Mg, Cl, bicarbonate, glucose
Indications: as in HD + a-v fistula failure, diabetes
mellitus
CI: abdominal wounds and adhesions
PD catheter (Tenckhoff´s): silicone, polyurethane
Catheter insertion technique: surgical, laparoscopy CAPD
(continuous ambulatory) - 4 exchanges a day
automated APD (cycler) – exchanges during nighttime
Complication: peritonitis
- abdominal pain, cloudy dialysis fluid >100 Le/µl
- culture: Staphylococcus SPA, Pseudomonas species etc.
KIDNEY TRANSPLANTATION
Donor: deceased (cadaveric), living (related, unrelated)
Compatibility: blood groups AB0, HLA system Transplanted kidney
is placed in iliac fossa
Complications: transplant rejection, infection Rejection
treatment: prednisone, tacrolimus, sirolimus,
mycophenolate mofetil, cyklosporin
DISORDERS OF ACID-BASE BALANCE Arterial blood pH 7,37–7,45
(norm)
Extracellular and intracellular buffers:
Bicarbonates (serum 35%, erythrocytes 18%)
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H+ + HCO3- ↔ H2CO3 ↔ H2O + CO2 ... (carboanhydrase)
Hemoglobin/oxyhemoglobin 35%, phosphates 5%, proteins 7%
Respiratory compensatory mechanisms:
Lungs and chemoreceptors in medulla oblongata are controlling
the
balance between formation and excretion of CO2, normal pCO2 in
arterial blood 40 mmHg (5,3 kPa).
Renal compensatory mechanisms:
Tubular reabsorption of filtrated HCO3,
Formation of titrated acids ... H+ + HPO42- → H2PO4-
Decreased urinary excretion of NH4+ ... H+ + NH3→ NH4+
Acid-base measuring devices determine pH, pCO2, pO2
Henderson-Hasselbalch equation:
HCO3¯
pH = 6,1+ log ––––––––––––––– pCO2 . 0,03
normal HCO3¯ in arterial blood 22–26 mmol/l normal BE (base
excess) in arterial blood –2 až +2 mmol/l
Disorders of acid-base balance: single, mixed; acute, chronic
Primary respiratory change → secondary metabolic renal response
Primary metabolic change → secondary respiratory response
Metabolic acidosis
Definition: arterial blood pH < 7,35 (severe pH
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(3) bicarbonate losses (GIT, kidneys)
Anion gap AG = Na+ – Cl¯ – HCO3¯ , normal 10-14 mmol/l,
concentration of unmeasured anions
MAC with high AG: diabetic ketoacidosis, lactate acidosis, ARF,
CRF (CKD stages 4 and 5),
exogenous toxins
MAC with normal AG (hyperchloremic): HCO3¯ losses: stool,
urinary in RTA
Decrease in blood pH by 0,1 increases serum K+ by 0,6
mmol/l.
Clinical presentation: hyperventilation, decreased
myocardium
contractility, dilation of peripheral arteries, constriction of
central veins, CNS sedation
Treatment:
pH 7,15–7,3 ... NaHCO3 tbl (1g NaHCO3 contains 12 mmol
HCO3¯).
pH 7,45 (severe pH>7,6), HCO3¯ Compensatory alveolar
hypoventilation increases pCO2
Causes: (1) ECV contraction, K+ deficit, secondary
hyperaldosteronism (2) Cl¯ deficit (vomiting, gastric juice
suction) (3) Renal causes (diuretics, K+ losses)
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(4) Increase exogenous intake of HCO3¯
Clinical presentation: hypoventilation, parestesia, muscular
twitching, dysrytmia, confusion
Treatment: Intravenous hypertonic NaCl solutions and KCl, if ECV
contraction, or K+
and Cl¯ deficits
Acetazolamide increases urinary excretion of NaHCO3¯. Proton
pump inhibitors in Cl¯ losses (gastric juice)
Acute hemodialysis
Respiratory acidosis
Definition: arterial blood pH < 7,35, pCO2
In chronic RAC renal compensatory mechanisms increase HCO3¯
Causes:
Acute: obstruction of airways, anaphylaxis, severe
bronchospasm
Chronic: central (CNS sedation, cerebral diseases),
bronchopulmonary (asthma,
COPD, restrictive disease), neuromuscular (thorax deformation,
myodystrophy, myasthenia), alveolar hypoventilation in obesity
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Clinical presentation:
Acute: dyspnoe, anxiety, confusion, coma
Chronic: somnolence, worsened locomotory coordination,
personality disorders
Treatment:
Acute: airways opening, tracheotomy, mechanical ventilation
Chronic: improvement of pulmonary ventilation.
Cautiousness in oxygenotherapy of spontaneously breathing
patient with
hyperkapnia Hyperkapnia should be lowered gradually (cerebral
hypoperfusion!)
Respiratory alkalosis
Definition: arterial blood pH>7,45, pCO2
In chronic RAL, renal compensatory mechanisms decrease HCO3¯
Increase in blood pH decreases serum ionized Ca2+
Causes:
central (anxiety, psychoses, fever, cerebral diseases)
hypoxemia (heart failure, pulmonary embolism, severe anemia)
medicaments (salicylates, methylxantines)
sepsis, mechanical assisted hyperventilation
Clinical presentation: Acute: parestesia, tetany, vertigo,
confusion
Chronic: mild RAL in chronic heart failure
Treatment: underlying disease