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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