Risk factors predicting urological complications of living-donor renal transplantation-A single center experience

 INTRODUCTION

A kidney transplant remains the preferable way to replace a kidney for the majority of cases in end-stage renal failure. However, it is not without risks. Individuals who underwent renal transplantation face a steady fight to survive for a long time. The large plurality of transplantation failure is referred to allogeneic immune-mediated injury, recurrent infections or glomerulonephritis, cardiovascular diseases and tumors. However, a number of kidney transplants are lost because of urological complications, especially in the early post-transplant period^1,2.

In spite of large improvement in the field of transplantation, a little minority of renal transplants are still lost because of urological complications. Some of these problems can be traced back to the period of retrieval and implantation. Serial

ultrasound screening of the transplanted kidney in the early post-operative period has essential role in early detection. The prognosis is commonly excellent if the complications are early detected and managed².

Therefore, recognizing these complications is extremely important for the multidisciplinary management of these patients³.

 The occurrence of urologic complications of renal transplantation varies vastly in the review. The gross occurrence ranges from 3.4–11.2%. intricacies like ureteral stricture, urine leak, symptomatic vesicoureteral reflux (VUR), urolithiasis, bladder outlet obstruction, and urinary tract obstruction from lymphocele are common . Complications are often known as early or late ^4,5.

The last decades have seen a considerable lowering in complication rates because of better realization of the biological behavior, development in the techniques of vascular and ureteric anastomosis, and the availability of effective regimens for immunosupression².

The purpose of the current study was to determine the incidence of urological complications after living donor renal transplantation, complications were correlated with pertinent risk factors and the influence of complications on graft survival was assessed.

PATIENTS AND METHODS

This is a retrospective case control study and was carried out at urology department in the national institute of urology and nephrology and included 240 patients who underwent renal transplantation in the period from 2011 to 2019, patients were followed up for at least two years.

Detailed history was taken from all patients included in the study, patients underwent full physical examination and laboratory investigations in the form of urine analysis, blood group, complete blood count , blood glucose, multiscreen panel (calcium, phosphate, AST, urea, creatinine, uric acid), electrolytes (sodium, potassium, chloride, CO2), total and direct bilirubin, albumin and total protein, lipid profile, serology (Hepatitis B, Hepatitis C, CMV, HIV) and human leukocyte antigen (HLA) typing.

Radiological studies included chest X-ray, kidneys, ureters, bladder (KUB) radiography, pelvi-abdominal ultrasound, electrocardiogram, echocardiography, aorto-iliac doppler and  ascending cystogram.

Patients underwent Triple Immunosuppression protocol (calcinurin inhibitor, mycophenolate and steroids).

The harvested kidney was immediately immersed in iced saline and perfused with crystalloid solution.

Regarding operative technique: patients were explored  via para-rectal, extraperitoneal approach, the right side was preferred  as the accessibility of the iliac vein made the operation easier than with the left side.

The peritoneum was withdrawn medially and the retroperitoneal space covering the iliac vessels was advanced. An autologous retractor was placed and the iliac vessels were exposed. Lymphatic tissue overlying the vessels was attached or closed off using electrocautery.

 The renal vein was anastomosed to the external iliac vein using proline 5/0 sutures in an end to side fashion, if there were multiple renal veins, the largest might be used, the others were ligated safely due to internal collateralization  of the renal venous drainage.

The renal artery was anastomosed using proline 6/0 sutures to the external iliac artery (in 221 cases) or the common iliac artery (in 19 cases) in an end to side way. Multiple donor arteries were encountered in 32 cases. In these cases the donor arteries were anastomosed individually or anastomosed to each other before being anastomosed to the recipient vessels. In most of our cases, the anastomosis ischaemia time ranged between 30 to 60 minutes  with a mean duration of 43 +_12.2 minutes. Immediate diuresis within 10 minutes after release of the vascular clamp was observed in most cases but in 23 cases the start of diuresis was delayed ranging from few minutes to few days.

The ureter was implanted in the bladder via an anti- reflux technique (extra-vesical Lich Gregoire technique) as it is simple, has low incidence of haematuria, requires a lower length of the ureter and is mostly faster than intravesical techniques, and the creation of an anti-flow tunnel inhibits reflux of infected urine into the allograft. Ureteral stents were inserted.  A closed suction drain was placed, Foley catheter was left for drainage of the bladder for 5-7 days.

In the first Post-operative day, investigations included CBC, creatinine, urea, sodium, potassium, renal duplex and pelviabdominal ultrasound.Urine output and CVP were evaluated.

Urine output and CVP were followed up every day, while CBC, creatinine, urea, sodium and potassium were followed up every other day for at least 5 days.

Renal duplex was repeated in the fifth postoperative day. Ultrasound CBC, creatinine, urea, sodium and potassium were repeated after 1 month and every 6 months, patients were followed up for at least two years.

Additional investigations were done for complicated cases in the form of urinalysis, urine culture and sensitivity for bacterial infection (UTI), ultrasound and CT for perinephric heamatoma, ultrasound and ascending cystogram for urinary leakage (urinoma), ultrasound for ureteral obstruction, ultrasound and CT for lymphocele, ascending cystogram for vesicoureteric reflux, and penile duplex for erectile dysfunction.

Statistical analysis: Data have been analyzed statistically by univariate and multivariate analysis utilizing SPSS (Statistical Package for Social Sciences) program version 22. To characterize the trial sample, quantitative results e.g. age have been summarized as minimum, maximum, mean and standard deviation. Qualitative results e.g. sex, was tabulated as count and percentage. Student’s t-test have been applied to compare continuous multivariate and the chi-squared test for categorical multivariate. In all tests, P < 0.05 have been considered to indicate significant differences, the survival of the graft and patients was calculated by using Kaplan-Meier technique with variations in survival computed with the long- rank test, Stepwise logestic regression was used for the multivariate analysis

RESULTS

This study included 240 patients that were subjected to renal transplantation.

Regarding the general characteristics of the patients, the mean age of the recipient was 41.62 years, while the mean age of the donor was 44.33 years. The male to female (M.F) ratio in the recipient was approximately 2:1, while in the donor was approximately 1.5:1.  The Incidence of double graft artery was 13.3%, while the incidence of double graft vein was 8.3% (Table 1).

Urological complications occurred in 26.3% of patients. Bacterial infection was demonstrated to be the most common early complication (in the first postoperative month) (8.8%), followed by perinephric hematoma (1.7%), urinary leakage (1.7%), ureteral obstruction (1.7%) and urinary retention (1.3%). Lymphocele was demonstrated to be the most common late complication(7.9%), followed by erectile dysfunction (2.1%), vesicoureteral reflux (1.7%) and  ureteral stricture (1.3%).

As regards the Graft function at the end of follow-up period in the studied sample, the majority of cases had functioning grafts (60.8%), while 33.3% and 4.5% of cases developed chronic kidney disease (CKD) and end stage kidney disease (ESKD) respectively (Table 2).

The mean Graft survival period in the current study was 37.05 ± 17.448 (median was 37 months) and ranging from 6 months to 70 months (Table 3).

Complication free cases demonstrated significant increase in survival in comparison with complicated ones (P<0.05) (Table 4).

The Kaplan Meier assessment of graft survival in the current study showed that the median complete success was 57 months and the median qualified success was more than 60 months (Table 5 and figure.)

The Univariate analysis for predictors of occurrence of urological complications showed that age of the recipient/ donor, gender of the recipient/ donor, diabetes, hypertension, chronic interstitial nephritis (CIN), lupus nephritis, double graft artery, double graft vein and operative duration were non-significant predictors (P>0.05) (Table 6).

Regarding the correlation between occurrence of urological complications and graft survival it was demonstrated that occurrence of urological complications significantly affects graft survival (P<0.05) (Table 7).

Table (1): General characteristics of the patients.

12 patients experienced multiple complications

Table 2: Incidence of urological complications, its onset and graft function at the end of follow-up period.

Table 3: Graft survival in the current study.

Table 4: Comparison of graft survival between patients with and without complications.

Table 5: Kaplan Meier assessment of graft survival in the current study.

Fig. 1: a-Kaplan Meier assessment of graft survival with complete success in the current study:

Fig. 1: b-Kaplan Meier assessment of graft survival with qualified success.

Exp(B): exponentiation of the B coefficient.

Table 6: Univariate analysis for predictors of occurrence of urological complications .

Table 7: Correlation between occurrence of urological complications and graft survival.