EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : CACUT, Complication after kidney transplant, End-stage renal disease, Renal transplant

Chronic kidney disease (CKD) remains a serious health problem worldwide, the incidence and prevalence of which is increasing every year. With regard to prevalence of CKD in children, in Europe, the prevalence ranges from 55 to 60 cases per million population, and the prevalence of stage 3 to stage 5 CKD is from 11 to 12 cases per million child population. The overall prevalence of end-stage renal disease (ESRD) is 80 cases per million child population.¹

Men have a higher incidence of CKD than women, and the incidence of congenital anomalies of the urinary tract is more common in male patients than in female patients.² Unlike adults who have reached physical and intellectual development, children with CKD are particularly vulnerable to complications of this disease. Congenital abnormalities of the kidneys and the urinary tract (CAKUT) are the most common reason for ESRD in children. The variety of causes of ESRD in children differs sharply from presently recognized causes in adults. About 30% of cases of ESRD in children are due to CAKUT. Given this anomaly in the treatment of these groups of patients, it is necessary to work together with groups of specialists such as pediatric urologists, surgeons, and nephrologists.

Common problems faced by pediatric nephrologists and urologists include prenatal hydronephrosis, obstructive uropathy (eg, posterior urethral valves), and vesicoureteral reflux (VUR).³ Given that this group of patients is often under the supervision of adult urologists and nephrologists, it is necessary to accurately understand and know the clinical picture, the features of these diseases, and the prognosis of these diseases.

Human effects on the environment and issues related to female reproductive health complications, including intrauterine and perinatal infections, drug treatments during pregnancy (such as aminoglycosides, cyclosporine A, prostaglandins, dexamethasone, furosemide, and cyclophosphamide), nephrotoxic drugs, and the presence of health problems such as iron deficiency anemia and folic acid deficiency, have been linked to an overall increase in the population of congenital malformations.⁴

In this study, our objective was to study the features of postoperative management and possible complications after kidney transplant in children.

Materials and Methods

We conducted a retrospective analysis of 29 children aged 9 to 18 years (mean age 13.96 ± 1.90 years) who underwent kidney transplant from April 2018 to December 2023. Our group included 17 male recipients (58.6%) and 12 female recipients (41.4%). All recipients were on hemodialysis for a duration of 3 to 18 months (mean duration of 10.17 ± 4.52 months). Incidence of urolithiasis in our study was 3 cases (10.3%). Of 29 patients, CAKUT was observed in 14 patients (48.3%); of these 14 patients, we observed VUR in 5 patients (17.2%). Chronic glomerulonephritis in 12 patients (41.4%) was the cause of ESRD. The donors were parents in 16 cases (55.2%), siblings in 5 (17.2%), uncles in 5 (17.2%), and aunts in 3 (10.4%), for whom human leukocyte antigen mismatches ranged from 2 to 5 (mean of 2.93 ± 1.39 mismatches). Three recipients had intraoperative nephrectomy (10.3%) (Figure 1), and 2 recipients (6.9%) had hydronephrosis and urethroplasty (Figure 2) with megaureter to prevent urinary tract infection.

Among our patients, complications after kidney transplant were divided into early postoperative complications and late postoperative complications. The following early postoperative complications were observed in 6 patients (20.6%): delayed graft function in 2 (6.9%), venous anastomosis thrombosis in 1 (3.4%), hematoma around the graft in 2 (6.9%), and lymphocele in 1 patient (3.4%). Venous anastomosis thrombosis was eliminated by open thrombectomy, and graft function was restored on postoperative day 17. The lymphocele was eliminated by puncture and drainage. The hematomas did not require surgical correction and blood transfusion.

The following late postoperative complications were observed in 10 patients (34.4%): stricture of vesicoureteral anastomosis in 1 (3.4%), VUR in 3 (10.3%), and urinary tract infection in 5 patients (17.2%; bacterial culture in 3 cases [60%] revealed Escherichia coli). The stricture of vesicoureteral anastomosis was successfully resolved by open surgery, which involved resection of the strictured distal ureter followed by reanastomosis. The VUR was eliminated using a polyacrylate-polyalcohol copolymer hydrogel (Vantris). In 1 case, chronic kidney rejection developed within 6 months because of noncompliance with the posttransplant regimen; this patient required a transplantectomy.

According to population studies from various sources, the tendency of newborn children to present with congenital malformations increases every year. Of these, 26% to 30% of cases are due to congenital malformations of the kidneys and organs of the urinary system. For example, the incidence of obstructive ureterohydronephrosis (megaureter) is 10% to 20%; male children often have obstructive forms of megaureter, whereas this manifests as VUR in female children.⁵ In our pediatric patients, 12 patients (41.4%) had chronic glomerulonephritis as the cause of ESRD; the literature has shown that the prevalence of CKD ranges from 15 to 74.7 cases per million children.⁶

Urolithiasis remains one of the most common types of nosology among children. Kidney and urinary tract stones are formed as a result of saturation of urine with oxalates, calcium, uric acid, and cystine. Most urinary tract stones in children are localized in the upper urinary tract. In 15% to 25% of cases in children, urolithiasis may be asymptomatic. The main diagnostic method for urolithiasis is ultrasonographic examination of the urinary tract, which detects both X-ray positive and X-ray negative stones (noncontrast stones). There is insufficient information in the world literature regarding prediction of relapses of urolithiasis and methods to eliminate such relapses. In our review of studies published during the past 20 years, we found no data on the frequency of urolithiasis in children. In some sources, the incidence of urolithiasis in children under 14 years of age has been reported as 19 to 20 cases per 100?000 children and in adolescents aged 14 to 18 years as 80 to 90 cases per 100?000 children.⁷ There were 3 cases of urolithiasis in our study.

The CAKUT syndrome has a different nature of occurrence. To date, the causes of the pathology of CAKUT are unknown. Among the main factors that have been associated with the development of CAKUT syndrome are (1) about 20% genetic mutations of the PAX2 gene and HNF1B gene and (2) external influences. In 10% to 20% of cases, the pathology is hereditary and is transmitted by an autosomal dominant mechanism; less often, CAKUT is transmitted by an autosomal recessive mechanism.⁸ Our study revealed CAKUT in 14 patients (48.3%), which is almost one-half of the surveyed group.

Common indications for nephrectomy in children are congenital nephritic syndrome with massive proteinuria (>40 mg/m²/h), polyuria (>2.5 mL/kg/h), drug-resistant hypertension, recurrent urinary tract infections with enlargement of the upper parts, malignant neoplasms or conditions that can lead to the development of malignant neoplasms in the future, and space-limiting cystic kidney disease.^9-11 In our study, intraoperative nephrectomy was performed in 3 patients (10.3%) with hydronephrosis.

Common causes of ESRD that require kidney transplant include congenital abnormalities of the kidneys and urinary tract, steroid-resistant nephrotic syndrome, chronic glomerulonephritis, and renal ciliopathies.² High-quality, early diagnosis and timely treatment are essential to reduce adverse outcomes and complications in children with urinary tract abnormalities. Our study identified possible types of early and late postoperative complications, as well as treatments, in children with different types of urinary tract disorders at our center. The lack of standardized treatment protocols and early diagnostic markers for these conditions is associated with the diverse nature of this pathology. For example, malformations can occur at different levels within the kidneys, ureters, bladder, or urethra. Pyeloectasia may not be detected until the child is older.

In pediatric nephrology, CAKUT syndrome is the widely accepted term to describe a combined condition known as congenital anomalies of the kidney and urinary tract. Investigation of the causes and consequences of CAKUT is an important concern for nephrologists, urologists, and geneticists alike. According to various sources, CAKUT syndrome accounts for approximately 30% of all abnormalities in the development of urinary tract organs that are associated with the formation of CKD. The birth rate of patients with CAKUT syndrome varies between 4 and 60 cases per 10?000 newborn children, according to different sources.^12,13 Our study also revealed that CAKUT syndrome accounts for almost one-half of the subjects studied.

In studies conducted from 1984 to 2007, delayed graft function was detected in 69% of cases. Delayed graft function has been the subject of much discussion but has traditionally been defined as the use of dialysis for 7 days after kidney transplant.^14,15 A more current and accurate definition of delayed graft function could be the failure to reduce serum creatinine levels by at least 10% for a period of 3 consecutive days during the first week after kidney transplant.¹⁶ In our study, we identified delayed graft function in 2 cases, which was restored on postoperative day 9. To restore graft function, hemodialysis treatments were administered, and pulse therapy with methylprednisolone was administered for 3 days (1.0 g, 0.5 g, and 0.5 g, respectively) to prevent acute graft rejection.

Graft thrombosis occurs in approximately 0.9% of patients within 1 month of transplant, which accounts for approximately 17% of early (within 30 days of transplant) graft failures.¹⁷ Among the patients who underwent surgery, thrombosis of the venous anastomosis of the graft occurred in 1 patient; timely diagnosis contributed to the determination of the appropriate course of action for this patient, which resulted in the restoration of graft function.

Pediatric transplant is crucial in the Republic of Uzbekistan because of the high prevalence of congenital urinary tract anomalies that contribute to nearly one-half of CKD cases. These abnormalities cause an increase in urinary tract infections, which significantly decrease after surgery. A major factor in reduction of the frequency of infections after surgery is the recipient’s nephrectomy.

Volume: 22 Issue: 10 October 2024 - Supplement - 5

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