The key code of medication for children's kidney transplantation (the frequency and dosage of medication)

Kidney transplantation is the best choice for treating end-stage renal disease in children, with 1-year and 5-year survival rates of 98% and 94% respectively. Compared with hemodialysis treatment, children who receive kidney transplantation not only have a higher survival rate, but also significantly improve their quality of life, and are also conducive to promoting catch-up growth in children. The following is an introduction to preoperative preparation, drug treatment, and complications of kidney transplantation in children.

Preoperative examination of kidney transplantation in children

Preoperative examinations for renal transplantation in children include laboratory tests, imaging examinations, urodynamic assessment, etc.

1. Laboratory examination: complete blood count, biochemical test, serum phosphorus and magnesium, parathyroid hormone, liver function, coagulation function, human leukocyte antigen and group reactive antibody, virus titer (cytomegalovirus, herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, hepatitis B virus, hepatitis C virus, human immunodeficiency virus), etc.

2. Imaging examination: chest X-ray examination and abdominal ultrasound examination. In addition, voiding cystourethrography, cystoscopy and other examinations are also required depending on the condition.

3. Urodynamic evaluation: including bladder capacity, bladder pressure, urine flow rate and ultrasonic bladder residual urine volume measurement. If low bladder capacity, high storage pressure, incomplete emptying or high urination pressure are found in the urodynamic examination, intervention is required before kidney transplantation to prevent urinary tract infection, urinary tract obstruction or urinary incontinence.

Drug therapy for renal transplantation in children

Regulating the normal immune response mechanism is an important prerequisite for the success of organ transplantation. Therefore, it is necessary to reduce the immune response through drugs such as immunosuppressants. Currently, commonly used immunosuppressants include: corticosteroids, antimetabolites, calcineurin inhibitors and antibodies, and the commonly used one is a combination of tacrolimus, mycophenolate mofetil and prednisolone.

Mechanism of action, medication recommendations and common adverse reactions of commonly used drugs for pediatric renal transplantation

Complications of kidney transplantation in children

Complications of kidney transplantation include surgical complications, urinary tract complications, postoperative infection, acute rejection, etc., as follows:

1. Surgical complications: cystic lymphangioma, wound infection, thrombosis, renal artery stenosis, etc.

●Cystic lymphangioma is the accumulation of lymph fluid around the kidneys, which usually manifests as graft fullness, pain, or decreased renal function. In severe cases, it can compress the pelvis and ureters, causing urinary tract obstruction and may also lead to venous obstruction. Ultrasound is the best examination method, and laparoscopic surgery is the preferred treatment method.

●Wound infection manifests as swelling, erythema, or purulent drainage from the incision, usually soon after kidney transplantation. Febrile patients with wound tenderness or swelling should undergo abdominal ultrasound or CT scan to detect the presence of perinephric effusion. If perinephric effusion occurs, surgical drainage should be performed immediately and antibiotics should be given.

●Thrombosis is one of the serious complications after kidney transplantation, with an incidence of 1% to 3%. It is mainly diagnosed by color Doppler ultrasound. Thrombosis may be caused by the recipient's hypercoagulable state. For patients who have experienced allogeneic transplant thrombosis, a thorough coagulation assessment should be performed before repeated transplantation. It should be noted that thrombosis needs to be diagnosed and treated in a timely manner, otherwise the consequences will be serious.

Renal artery stenosis can be caused by anastomotic constriction, renal artery kinking, or segmental thickening of the renal artery intima or its branches, with an incidence of 1% to 5%. Digital subtraction angiography is the most sensitive diagnostic test. Treatment options include balloon angioplasty or open revascularization, of which balloon angioplasty has a higher success rate and a lower risk of complications.

2. Urinary tract system complications: including urinary tract obstruction and urine leakage.

●Urinary tract obstruction can be caused by surgical errors or distal ureteral ischemia, with an incidence of 2% to 4%. Ultrasound is the best method for diagnosing obstruction. Treatment options include balloon dilatation or ureterostomy.

●Urinary leakage manifests as incisional leakage, which is usually caused by rupture of the ureteral anastomosis to the bladder. Large and persistent leakage usually requires surgical repair.

3. Postoperative infection: Infection is one of the most important and common complications of kidney transplantation. It may occur at any time after transplantation, most commonly in the first 6 months after transplantation. The severity varies greatly and can significantly increase the mortality rate of children. Post-transplant infection can be caused by bacteria, viruses, fungi, mycobacteria and other microorganisms.

●Urinary tract infection is the most common post-transplant infection, with an incidence of up to 30%. Its treatment depends on the severity of the infection. Children with UTI and fever, nausea, myalgia, or other systemic symptoms should receive broad-spectrum parenteral antibiotics; children with UTI who are afebrile can be treated with oral antibiotics. Gram-negative bacilli are common bacteria that cause post-transplant urine infection; therefore, antibiotics that are sensitive to Gram-negative bacilli can be used for treatment before urine culture results are available.

●Viral infections include cytomegalovirus, Epstein-Barr virus, herpes simplex virus, varicella-zoster virus, and BK polyomavirus. Among them, cytomegalovirus infection rate is relatively high, and up to 90% of children will develop cytomegalovirus in the first 3 to 6 months after transplantation.

4. Acute rejection: including acute rejection and chronic allogeneic transplant nephropathy. With the application of more specific immunosuppressants, immune reactions after kidney transplantation are becoming less and less. However, rejection is still the most common cause of allogeneic kidney loss in children and adults.

●Acute rejection is an immune response to the allograft that can lead to a rapid decline in renal function, usually manifested by a rapid rise in serum creatinine without other signs or symptoms. Severe acute rejection may cause fever, myalgia, graft pain, or decreased urine output, and renal biopsy is the most reliable diagnostic test. Mild acute rejection can be treated with a short-term pulse of corticosteroids [5 mg/(kg·d) IV for 3 days, then tapered to baseline steroid dose over 7 to 10 days]. Acute rejection that does not respond to steroid pulse therapy and severe acute rejection can be treated with antilymphocyte antibodies.

●Chronic allograft nephropathy is defined as an immune response to the allograft that leads to a gradual and sustained decline in renal function, usually manifested as a gradual increase in serum creatinine. Patients are asymptomatic and require a renal biopsy for diagnosis. There is currently no effective treatment for chronic allograft nephropathy, and preventing acute rejection is the best way to avoid its occurrence.

References: [1] Verghese PS. Pediatric kidney transplantation: a historical review. Pediatr Res. 2017 Jan;81(1-2):259-264. doi: 10.1038/pr.2016.207. Epub 2016 Oct 12. PMID: 27732587.