Kidney transplantation

Kidney transplantation is the most common type of solid organ transplantation; the main indication is end-stage renal disease. Absolute contraindications include comorbidities that may compromise graft survival (eg, severe cardiac disease, malignancy) and are detectable on evaluation. A relative contraindication is poorly controlled diabetes, which may lead to renal failure. Patients over 60 years of age may be candidates for transplantation if they are generally healthy, functionally independent, with good social support, with a relatively good prognosis for survival, and if kidney transplantation is expected to substantially improve quality of life without dialysis. Patients with type I diabetes may also be candidates for transplantation provided they have undergone simultaneous pancreas-kidney or pancreas-after-kidney transplantation.

More than 1/2 of donor kidneys come from healthy, brain-dead individuals. About 1/3 of these kidneys are marginal, with physiological or procedural impairments, but are used because the need is so great. The remaining donor kidneys come from living donors; because organ supply is limited, aplotransplants from carefully selected living unrelated donors are increasingly used.

The main methods of treating patients with terminal stage chronic renal failure are programmed hemodialysis and kidney transplantation. The need for continuous hemodialysis procedures for detoxification forces the patient to visit a specialized clinic every two or three days and is often accompanied by significant iatrogenic complications (bleeding, anemia, dizziness, fainting, the possibility of infection with viral hepatitis, etc.). At the same time, kidney transplantation can give radically better results in case of successful operation, providing almost optimal quality of life. The level of perioperative mortality and life expectancy after transplantation differ significantly from similar indicators in patients on hemodialysis. Therefore, a significant number of adults with terminal stage kidney disease are candidates for kidney transplantation.

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Anatomical and physiological features of the urinary system and pathophysiological changes in terminal renal failure

There are many causes of end-stage renal failure: diabetic nephropathy, glomerulonephritis of various etiologies, polycystic kidney disease, chronic pyelonephritis, obstructive uropathy, Alport syndrome, lupus nephritis and others, including cases of unknown etiology. Impaired renal function of any etiology ultimately leads to the development of uremic syndrome. With uremia, patients are unable to regulate the volume and composition of body fluids, which leads to fluid overload, acidemia and imbalance of electrolytes such as potassium, phosphorus, magnesium and calcium. Signs of progressive secondary dysfunction in other body systems develop. Even patients supported by hemodialysis may experience peripheral neuropathy, pericardial or pleural effusions, renal osteodystrophy, gastrointestinal and immunological dysfunction.

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Premedication

Diazepam IM 10-20 mg, once 25-30 minutes before the patient is taken to the operating room or Midazolam IM 7.5-10 mg, once 25-30 minutes before the patient is taken to the operating room

Chloropyramine IM 20 mg, once 25-30 minutes before the patient is taken to the operating room

Cimetidine IM 200 mg, once 25-30 minutes before the patient is taken to the operating room

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Betamethasone IM 4 mg, once 25-30 minutes before the patient is taken to the operating room.

Patients may be given immunosuppressants before surgery. There are various treatment options, but the most commonly used are cyclosporine, azathioprine, and corticosteroids. Methylprednisolone is often given intravenously at the induction of anesthesia or just before blood flow to the graft is restored. Immunosuppressants have many side effects, but particular attention should be paid to muromonab-CD3 (a monoclonal antibody against T lymphocytes), which can cause pulmonary edema and seizures.

Preoperative preparation and assessment of the patient's condition before surgery

In living related donor transplantation, detailed donor examination is virtually unlimited in time and must be carried out carefully and routinely.

Cadaveric kidney recipients may be called to the hospital urgently when a suitable organ is available and are then treated as emergency surgery patients. Key basic investigations include:

• determination of hemoglobin, creatinine, urea and electrolyte levels;
• ECG;
• chest x-ray.

Depending on the fluid balance and metabolic status, patients may undergo hemodialysis prior to surgery to correct hyperkalemia and acid-base balance disorders. After dialysis, it is important to establish the volume status of patients, the final hematocrit, electrolyte and bicarbonate levels, and whether there is a residual effect of heparin. Plasma potassium and calcium levels should be normal to exclude the occurrence of arrhythmias, cardiac disorders, and seizures. Hypovolemia should be avoided, since hypotension increases the possibility of acute tubular necrosis (ATN) in the graft.

Patients with severe uremia, even on dialysis, have a hematocrit level of 6-8 g/dl. Prothrombin time and partial thromboplastin time are usually normal, but hypocoagulation remaining after dialysis should be corrected before surgery. It should be remembered that uremia leads to prolongation of bleeding time.

Many patients had severe anemia before the use of recombinant erythropoietins and often required perioperative blood transfusions. Now, treatment with erythropoietins is used to maintain Hb at 9.5 g/dL to improve exercise tolerance. However, erythropoietins can worsen hypertension and lead to increased coagulation.

If functional impairment is present due to pleural or pericardial effusions, these may need to be treated. Because many adult recipients have diabetes, the presence of concomitant ischemic heart disease is usually determined by exercise testing and, if necessary, coronary angiography.

Renal transplant candidates typically present with delayed gastric emptying due to diabetes, peripheral neuropathy, and preoperative anxiety. Preoperative use of H2-receptor antagonists, antiemetics, metoclopramide, or sodium citrate may be appropriate. Premedication with anxiolytics such as midazolam or diazepam may be necessary. As in all emergencies, rapid induction and intubation of the patient is essential.

Basic methods of anesthesia

Currently, kidney transplantation uses various types of general combined anesthesia, the components of which may include:

• IA;
• IV anesthesia;
• RAA.

With general combined anesthesia, along with reliable analgesia, muscle relaxation and neurovegetative protection, control of mechanical ventilation is ensured, which becomes especially important during surgical manipulations near the diaphragm, therefore, OA is usually the method of choice.

Kidney transplantation successfully uses RAA methods - epidural and spinal anesthesia as components of general combined anesthesia. However, the risk of neurological complications with a long-term presence of a catheter in the epidural space may increase due to a combination of possible hypotension and hypocoagulation, especially against the background of initial excessive heparinization after hemodialysis. RAA can complicate the assessment of intravascular volume and the situation with volume preload. Induction of anesthesia: Hexobarbital IV 3-5 mg / kg, single dose or Thiopental sodium IV 3-5 mg / kg, single dose

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Fentanyl IV 3.5-4 mcg/kg, single dose

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Midazolam IV 5-10 mg, single dose million

Propofol intravenously 2 mg/kg, single dose

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Fentanyl intravenously 3.5-4 mcg/kg, single dose.

Muscle relaxation:

Atracurium besylate IV 25-50 mg (0.4-0.7 mg/kg), single dose or Pipecuronium bromide IV 4-6 mg (0.07-0.09 mg/kg), single dose or Cisatracurium besylate IV 10-15 mg (0.15-0.3 mg/kg), single dose. Induction of anesthesia can be performed with propfol, thiopental or etomidate while monitoring hemocytic parameters. Drugs that have a high affinity for proteins (e.g. thiopental) should be administered in reduced doses. Propofol is successfully used for TIVA, its advantage is considered to be a reduction in PONV syndrome.

If incomplete gastric emptying is suspected (especially in the presence of gastroesophageal reflux or peripheral neuropathy), rapid induction and intubation are indicated.

Since most of these patients have hypertension, benzodiazepines (midazolam 5-15 mg) and fentanyl 0.2-0.3 mg are widely used to reduce the stress response to laryngoscopy and tracheal intubation.

Nondepolarizing muscle relaxants (atracurium besylate and cisatracurium besylate) are used predominantly for intubation. Their use is justified because excretion of these drugs does not depend on renal function and they are destroyed by Hoffman elimination. Atracurium besylate and cisatracurium besylate are the preferred muscle relaxants because they are the least dependent on renal metabolism, although laudanosine, a metabolite of atracurium, may accumulate in patients with end-stage renal failure. Laudanosine increases the MAC of halothane in laboratory animals but does not cause a similar clinical result in humans. The response to vecuronium bromide may be unpredictable in renal disease, and neuromuscular monitoring is recommended during recovery of renal metabolic function after transplantation. The use of pipecuronium bromide and pancuronium bromide is best avoided, as their action may be prolonged due to the fact that 80% of these drugs are eliminated through the kidneys.

Kidney transplantation makes little use of depolarizing muscle relaxants. Suxamethonium chloride at the intubation dose in patients with renal failure may increase plasma potassium by an average of 0.5 mmol/L (maximum 0.7 mmol/L). Cardiac arrest and death have been reported in patients with preexisting hyperkalemia when suxamethonium chloride is re-administered. Normal plasma potassium levels achieved by recent hemodialysis are not a contraindication to the use of suxamethonium chloride. It should not be administered to patients with plasma potassium levels greater than 5.5 mmol/L or to those with uremic neuropathy. In these circumstances, the technique of sequential rapid induction is modified and suxamethonium chloride is not used.

Maintenance of anesthesia:

(general balanced anesthesia based on isoflurane) Isoflurane by inhalation 0.6-2 MAC I (in minimal-flow mode)

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Dinitrogen oxide with oxygen by inhalation 1:1 (0.25:0.25 l/min)

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Fentanyl intravenously bolus 0.1-0.2 mg, frequency of administration is determined by clinical appropriateness +

Midazolam IV bolus 0.5-1 mg, frequency of administration is determined by clinical appropriateness or (TVVA) I Propofol IV 1.2-3 mg/kg/h

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Fentanyl intravenously bolus 0.1-0.2 mg, frequency of administration is determined by clinical appropriateness or

(general combined anesthesia based on prolonged epidural block)

Lidocaine 2% solution, epidural I 2.5-4 mg/kg/h

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Bupivacaine 0.5% solution, epidural 1-2 mg/kg/h

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Fentanyl IV bolus 0.1 mg, frequency of administration is determined by clinical appropriateness

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Midazolam intravenously bolus 1 mg, frequency of administration is determined by clinical appropriateness.

Muscle relaxation:

Atracurium besylate 1-1.5 mg/kg/h or Cisatracurium besylate 0.5-0.75 mg/kg/h. Isoflurane is the drug of choice among inhalation anesthetics, since only 0.2% of this drug is metabolized.

Isoflurane produces inorganic fluoride ions in very small quantities and rarely causes cardiac arrhythmias. Isoflurane also has the least effect on CO and renal blood flow compared to other inhalational anesthetics.

Sevoflurane is very promising for use in transplantology due to its minimal impact on liver and kidney function. Recent studies have shown that it can be used without restrictions in low- and minimal-flow fresh gas flow modes.

Enflurane does not have significant side effects on graft function, but inorganic fluoride ion levels reach 75% of the nephrotoxic level, and therefore enflurane is not recommended.

Halothane is still widely used, but it should be remembered that in patients with CRF its arrhythmogenic potential may increase.

Dinitrogen oxide is often excluded from the gas anesthetic mixture to avoid intestinal distension, especially in children.

Fentanyl is used in normal doses because its excretion occurs primarily through metabolism in the liver.

Morphine may cause prolonged effects such as sedation and respiratory depression in renal failure due to accumulation of its active metabolite, morphine-6-glucuronide.

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Adjuvant therapy

In adults, the kidney is implanted retroperitoneally in the upper pelvis using a paramedian lower abdominal approach. In children weighing less than 20 kg, implantation into the abdominal cavity is usually used. In adult graft revascularization, the renal vessels are anastomosed to the iliac vein and artery. This may require clamping of the common iliac vessels, resulting in limb ischemia typically lasting up to 60 minutes. Once the anastomosis is complete, circulation to the graft and limbs is restored.

After the vascular clamps are removed, the renal preservative solution and the deposited venous blood from the limb enter the general circulation. This outflowing blood is relatively rich in potassium and acid metabolites, which can have a pronounced systemic hypotensive effect even in adults. The final stage of the operation involves ureteral implantation for urinary drainage.

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Stimulation of primary renal transplant function

To stimulate renal perfusion, blood pressure is maintained above normal, which can be achieved either by reducing the depth of anesthesia or by bolus administration of crystalloids and temporary infusion of dopamine. The main components of infusion therapy are crystalloids (sodium chloride/calcium chloride, isotonic saline, K+-free balanced salt solutions) and FFP:

Dopamine IV 2-4 mcg/kg/min, duration of administration is determined by clinical appropriateness

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Sodium chloride, 0.9% solution, intravenously 6-8 ml/kg/h, the duration of administration is determined by clinical appropriateness

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Fresh frozen plasma intravenously 4-6 ml/kg/h, duration of administration is determined by clinical appropriateness

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Albumin IV 3 ml/kg, duration determined by clinical appropriateness. As a rule, it is recommended to minimize IV fluid administration during surgery in patients with end-stage CRF in order to prevent fluid overload and reduce the need for postoperative dialysis. Kidney transplantation represents an important exception to this rule. When vascular clamps are removed, good perfusion of the new transplanted kidney is essential for immediate graft function, which is directly dependent on adequate intravascular volume and the absence of hypotension. The target CVP should be equal to or greater than 10-12 mmHg or, if a pulmonary artery catheter is present, diastolic PAP should be greater than or equal to 15 mmHg. Lower values are associated with a higher risk of AKI in the transplanted kidney. However, significantly larger volumes of fluid may be required to achieve relative hypervolemia. Typical volumes in some studies have been 60-100 ml/kg, emphasizing the need for CVP monitoring. Most authors consider the type of IV fluid to be less important. Isotonic 0.9% sodium chloride is the drug of choice because it contains a large amount of sodium (especially important if mannitol was used) and does not contain potassium or lactate. FFP and albumin are transfused in large volumes. Blood transfusions are given only when indicated. Intraoperative blood loss is usually less than 500 ml, but sudden massive hemorrhage cannot be ruled out. Sometimes, removal of vascular clamps results in significant blood loss, which must be quickly replaced to maintain perfusion of the transplanted kidney.

Diuretics are administered to stimulate immediate function of the transplanted kidney and increase urine production. Furosemide is administered as a single bolus immediately before removing the clamps from the restored renal artery and vein at a dose of 2 mg/kg and then repeatedly at a dose of 6 mg/kg over an hour using a perfusor. It should be noted that if the kidney is successfully included in the bloodstream with a favorable picture of its filling with blood and with rapid restoration of urine production by the kidney, the second dose of furosemide may be administered incompletely or canceled altogether. This is due to the risk of developing polyuria in the early postoperative period, which is especially important in related kidney transplantation.

Simultaneously with the infusion of the second dose of furosemide, dopamine is administered at a "renal" dose of 2 mcg/kg/min using a perfusor. Dopamine is often used to achieve two goals. There is a theoretical justification for its use as a DA2 receptor agonist at a dose of 2-3 mcg/kg/min to ensure renal blood flow. However, it has not been shown to improve graft survival, which may be due to the vasoconstriction caused by cyclosporine. At doses of 5-10 mcg/kg/min, the beta-adrenergic effects may help to maintain normotension. At higher doses, the alpha-adrenergic effects of dopamine predominate and blood flow in the grafted kidney may actually be reduced. If hypotension remains a problem despite adequate volume resuscitation, beta-agonists such as dobutamine or dopexamine are preferred. Stimulation of diuresis:

Furosemide IV bolus 2 mg/kg, then IV over an hour using a perfusor 6 mg/kg

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Dopamine intravenously 2 mcg/kg/min after starting blood flow through the kidney, the duration of administration is determined by clinical appropriateness.

Kidney transplant procedure

The donor kidney is removed by open or laparoscopic surgery and perfused with cooled solutions containing relatively high concentrations of poorly penetrating substances (mannitol, heta-starch) and an electrolyte concentration approaching intracellular levels; the kidney is stored in frozen solution. With this method of preparation, renal function is well preserved, provided that the kidney is transplanted within 48 hours. If the kidney is not used during this time, ex vivo viability of the kidney can be increased to 72 hours by continuous pulsatile hypothermic perfusion with oxygenated, plasma-based perfusion solution.

Dialysis may be required before transplantation to ensure a relatively normal metabolic state, but living donor allografts survive better than recipients who have not been on long-term dialysis before transplantation. Nephrectomy is usually not required unless there is infection in the native kidneys. It is not known whether transfusion is beneficial in anemic patients who will receive an allograft; transfusion may sensitize patients to alloantigens, but allograft survival may be better in transfused but not sensitized recipients; this may be because transfusion induces some form of tolerance.

The transplanted kidney is usually placed in the iliac fossa. Anastomoses of the renal vessels with the iliac vessels are formed, the donor ureter is implanted in the bladder or an anastomosis is formed with the recipient's ureter. Vesicoureteral reflux is observed in 30% of recipients, but usually does not have serious consequences.

Immunosuppressive regimens vary. Typically, cyclosporine is given intravenously during or immediately after transplantation and orally thereafter at doses that minimize toxicity and risk of rejection, and to maintain blood levels above 200 ng/mL. Glucocorticoids are also given intravenously or orally on the day of transplantation; the dose is tapered to a minimum over the next 12 weeks.

Despite the use of immunosuppressants, most recipients experience one or more episodes of rejection. Most cases are probably minor, subclinical, and therefore never detected; however, they contribute to graft failure, damage, or both. Signs of rejection vary depending on the type.

If the diagnosis is clinically unclear, rejection can be diagnosed by percutaneous needle biopsy. Biopsy helps differentiate between antibody-mediated and T-cell-mediated rejection and identify other causes of graft failure or injury (eg, calcineurin inhibitor toxicity, diabetic or hypertensive nephropathy, polyomavirus type 1 infection). More definitive tests to clarify the diagnosis of rejection include measurement of urinary mRNA encoding rejection mediators and genetic expression profiling of biopsy specimens using DNA microarrays.

Chronic allograft nephropathy results in graft failure or damage within 3 months of transplantation. Most cases occur for the reasons listed above. Some experts suggest that the term should be reserved for graft failure or damage when biopsy shows that chronic interstitial fibrosis and tubular atrophy are not due to any other cause.

Intensive immunosuppressive therapy (eg, with high-dose pulse glucocorticoids or antilymphocyte globulin) usually reverses accelerated or acute rejection. If immunosuppressants are ineffective, the dose is tapered and hemodialysis is resumed until another graft is found. Nephrectomy of the transplanted kidney is necessary if hematuria, graft tenderness, or fever develops after immunosuppressants are discontinued.

Kidney transplantation in children

Unlike adults, pediatric kidney transplants utilize intra-abdominal placement of the organ. This allows an adult kidney, i.e. a large organ, to be placed inside a very small child, thereby increasing the pool of potential donors. However, placement of a cooled graft may cause acute hypothermia and take up a relatively large circulating blood volume of the child. Hypotension caused by these factors occurs at the moment when adequate graft perfusion is needed. To prevent hypotension and acute nephropathy as its immediate consequence, vasoactive drugs are used to maintain blood pressure within normal limits. As a rule, kidneys taken from living related donors usually function immediately, while cadaveric kidneys are characterized by a delayed function - resumption of urine production only after several hours. This must be taken into account when performing infusion therapy. In any case, an adult kidney will initially produce urine volumes of an adult, which must be taken into account when performing maintenance infusion therapy.

Correction of violations

Temporary periods of oliguria or anuria, which are a consequence of AKI, occur in one third of cadaveric transplants. Therefore, the volume of infusion therapy should be calculated in such a way that, with a sufficient level of relative hypervolemia, the risk of intra- and postoperative pulmonary edema is avoided. The ischaemic time for organs obtained from living related donors is minimal, and urine output is usually observed immediately (primary graft function).

Awakening is often accompanied by pain and hypertension, which are especially dangerous in patients with diabetes and concomitant coronary artery disease. In such cases, potent analgesic drugs (opioids, tramadol or local anesthetics via epidural catheter) and antihypertensive drugs should be used to avoid myocardial ischemia.

Other early postoperative complications include atelectasis, bleeding and thrombosis of vascular anastomoses, ureteral obstruction or leakage, and aspiration of gastric contents. Hyperacute rejection may occur, leading to anuria; definitive diagnosis requires renal biopsy. This complication has become quite rare since ABO compatibility testing and cross-matching of recipient serum to donor lymphocytes are routinely performed.

Immunosuppression with "triple therapy" (cyclosporine, azathioprine, prednisolone) is usually started before living related donor organ transplantation or after cadaveric kidney transplantation.

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Kidney transplantation: contraindications

Major contraindications to kidney transplantation include active malignancy or infection, severe cardiovascular disease, recent myocardial infarction, and end-stage diseases of other systems. Relative contraindications specific to kidney transplantation include conditions that may relapse in the transplanted kidney, such as hemolytic uremic syndrome, membranoproliferative glomerulonephritis, and metabolic disorders that cause toxic deposits in the kidney (eg, gout, oxalosis). However, patients with such problems may remain in good condition for many years after transplantation, and this option is often considered appropriate. Diabetic nephropathy may also recur in the graft, but diabetes mellitus is no longer considered a contraindication to transplantation, and the most successful and promising are simultaneous kidney and pancreas transplants. The presence of combined liver and kidney damage with clinical manifestation of renal and hepatic failure is also no longer an insurmountable obstacle. Successful experience of combined simultaneous liver and kidney transplants, including from a related donor, convinces of the wide possibilities of performing such operations.

What is the prognosis for kidney transplantation?

The greatest number of cases of rejection and other complications occur within 3-4 months after transplantation; most patients regain their normal health and activity, but must take maintenance doses of immunosuppressants on an ongoing basis.

At 1 year, survival rates for living donor transplants are 98% for patients and 94% for grafts; for cadaveric donor transplants, these rates are 94% and 88%, respectively. Thereafter, annual graft loss is 3-5% for living donor kidney transplants and 5-8% for cadaveric kidney transplants.

Of patients whose grafts survive longer than 1 year, 1/3 die of other causes with a normally functioning graft; 1/3 develop chronic allograft nephropathy with graft dysfunction occurring within 1 to 5 years. The incidence of late disorders is higher in black patients than in white patients.

Doppler ultrasound measurement of peak systolic and trough end-diastolic flow in renal segmental arteries 3 months or more after a procedure such as renal transplantation can help assess prognosis, but the "gold standard" remains periodic determination of serum creatinine.

Monitoring

Routine ECG monitoring (preferably with ST-shift monitoring) should be initiated before induction of anesthesia. Neuromuscular and temperature monitoring (central and peripheral temperature) should also be used. Hypothermia leads to vasoconstriction, increases bleeding, and complicates fluid management during rewarming. Normothermia should be maintained using heated mattresses, air warmers, and warming of IV fluids.

Monitoring of CVP is mandatory, since it is the main available parameter in the assessment of intravascular volume, although central venous stenosis is quite common in patients receiving dialysis through central venous lines. Monitoring with a pulmonary artery catheter and invasive measurement of BP may be required in patients with severe cardiovascular diseases. Continuous monitoring of systemic BP can ensure that any of its dynamics will not go unnoticed. Sudden and extremely rapid changes in BP, typical for patients with CRF, are unacceptable during acute reperfusion, since the degree and speed of hypotension largely determine the incidence of AIO in the postoperative period. The task of the anesthesiologist is to promptly detect the first signs of hypotension and their timely and adequate correction.

Evaluation of the patient's condition after surgery

The duration of the operation (3-5 hours), the use of drugs with predominantly extrahepatic metabolism suggest the possibility of early extubation on the operating table. Therefore, the main attention in the early postoperative period should be paid to the prevention of nausea and vomiting, effective oxygenation using a continuous supply of oxygen through a Hudson mask, eliminating the prerequisites for the development of hypothermia, preventing the occurrence of chills and muscle tremors. For this purpose, heated mattresses, thermal blankets, wrapping the patient in blankets, foil, etc. are used. Adherence to an adequate temperature regime is of great importance, since the procedure for early extracorporeal detoxification using plasmapheresis, which has been very often used recently in kidney transplantation, can significantly reduce body temperature. In conditions of actively continuing infusion therapy, especially in the presence of paradoxical polyuria, constant control of volemia is very important, which is carried out by constant or periodic monitoring of the central venous pressure.

It should be noted that there is a tendency for early activation of patients with a transplanted kidney. A large range of motion and the ability to walk by the end of the first day of the postoperative period should imply extremely careful monitoring of patients by the staff.

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