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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 2  |  Issue : 1  |  Page : 31-35

Outcomes of pediatric renal transplantation at a single center


1 Resident in Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India
2 Consultant Nephrologist, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India

Date of Web Publication17-May-2019

Correspondence Address:
Mital Parikh
A/5 Vrundavan Park Society, VIP Road, Karelibaug, Vadodara - 390 018, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJPN.AJPN_1_19

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  Abstract 


Introduction: Renal transplantation is the preferred treatment option for children with end-stage renal disease (ESRD). There is scant information on comparative outcomes of pediatric renal transplantation in centers in developing regions. Materials and Methods: We retrospectively reviewed outcomes of renal transplantation in pediatric recipients of renal transplantation at a single center between 2001 and 2018. Information of underlying etiology of ESRD, pretransplant renal replacement therapy (RRT) modality, donor type, immunosuppression regimen, surgical complications, rates of rejection, compliance to immunosuppression, graft survival, and overall patient survival is presented. Results: Of 100 patients (77 boys) who received transplantation at the mean age of 15.7 ± 2.3 (5–18) years, chief underlying etiology of ESRD was chronic glomerulonephritis (n = 19), chronic tubulointerstitial nephritis (n = 31), and Alport syndrome (n = 1). Modality of RRT was predominantly hemodialysis (n = 90) or peritoneal dialysis (n = 6). Allograft survival was 98%, 85%, 80%, and 73% at 1, 3, 5, and 10 years, respectively. No deaths were observed. Conclusions: Pediatric renal transplantation at a single center in India was associated with satisfactory short-term patient and allograft outcomes. Rates of allograft survival at 10-year follow-up were lower as compared to other unicentric reports from the region.

Keywords: ABO-compatible, children, kidney transplant, live-related donor


How to cite this article:
Parikh M, Hedge U, Konnur A, Gang S, Rajapurkar M, Patel H, Patel N. Outcomes of pediatric renal transplantation at a single center. Asian J Pediatr Nephrol 2019;2:31-5

How to cite this URL:
Parikh M, Hedge U, Konnur A, Gang S, Rajapurkar M, Patel H, Patel N. Outcomes of pediatric renal transplantation at a single center. Asian J Pediatr Nephrol [serial online] 2019 [cited 2019 Oct 23];2:31-5. Available from: http://www.ajpn-online.org/text.asp?2019/2/1/31/258555




  Introduction Top


Renal transplantation is the preferred modality of renal replacement therapy (RRT) in children with end-stage renal disease (ESRD). It improves well-being dramatically, with the disappearance of fatigue and anorexia and accelerated growth which has a significant impact on the quality of life.[1],[2] The time saved from dialysis, i.e., disability-adjusted life years after kidney transplantation is several thousands of hours/year.[3] There is a paucity of data on the long-term outcomes of pediatric renal transplantation from developing countries. This retrospective study evaluates the outcome of pediatric renal transplantation at a tertiary center in India and compares it with those reported from other centers in India.


  Materials and Methods Top


Following approval from the Institutional Review Board, we retrospectively reviewed clinical records of children who underwent live renal transplantation between 2001 and 2018 to determine the etiology of ESRD, relationship to donor, procedure of kidney retrieval, immunosuppression regimen, occurrence of surgical complications, allograft rejection and infections, compliance to immunosuppression, and allograft and patient survival at 1, 3, 5, and 10 years of follow-up.

Transplant surgery

Choice between laparoscopic and open donor nephrectomy was based on the surgeon's discretion. Renal transplantation was performed by the standard open surgical technique with right pararectal incision using an extraperitoneal approach. Arterial anastomosis was with the common or external iliac artery in an end-to-side manner, or to the internal iliac in an end-to-end manner, depending on the recipient and donor vascular anatomy. Venous anastomosis was performed with the external iliac vein in an end-to-side manner. For ureterovesical anastomosis, the modified Lich-Gregoir technique was used, and a double J stent was placed that was removed later, usually on the 10th postoperative day.

Immunosuppression protocol

All patients received 300–500 mg/m2 of methylprednisolone intravenously (IV) on the day of transplant. Till 2004, cyclosporine was used, in a dose of 8–10 mg/kg, to maintain trough levels of 150–250 ng/ml in the first 3 months posttransplant, and 75–100 ng/ml thereafter. Azathioprine was administered at 1.5 mg/kg/day. Prednisolone was administered initially at a dose of 1 mg/kg/day and gradually tapered to 0.5 mg/kg/day by the end of 3 months. After 2004, the immunosuppressive regimen was changed, with gradual switch from the use of cyclosporine and azathioprine to tacrolimus and mycophenolate mofetil (MMF). Tacrolimus and MMF were administered, at doses of 0.1 mg/kg/dose and 600 mg/m2/dose twice daily each, respectively. Tacrolimus dose was titrated to reach a target trough level of 10–12 ng/mL by 3 months and lower levels thereafter.

Follow-up

Patients were followed up biweekly for the 1st month, weekly for the next 2 months, and 2–3 monthly thereafter. Compliance was assessed with the medication history (frequency/day, dosages, and names of drugs) obtained from patients and confirmed with guardians. Patients who missed >1 dose of any immunosuppressive drug in a week were assessed as being noncompliant.

Complications

Persistent urinary leak was defined as >100 mL of drain output beyond the 7th postoperative day, with drain fluid creatinine of more than ten-fold the serum value; if the fluid was not consistent with urine, it was termed persistent lymphorrhea. Delayed allograft function was defined as the need for dialysis in the 1st week of transplant.[4] Persistence of serum creatinine at or >2 mg/dL for >3 months was termed chronic allograft dysfunction.[5] Allograft loss was the need for nephrectomy, persistent rise of serum creatinine to 5 mg/dL or higher, or patient death with a functioning graft.[5]

Episodes of acute rejection (AR) were diagnosed based on the clinical suspicion and/or elevation of serum creatinine >30% of the nadir value and allograft Doppler and biopsy. Cyclosporine or tacrolimus trough level was estimated to exclude calcineurin inhibitor (CNI) toxicity as a cause of allograft dysfunction. Acute cellular rejection was treated with methylprednisolone 600 mg/m2 daily for 3 days. Steroid-resistant rejections, defined as the failure of serum creatinine to return to within 30% of baseline value by day 5 of therapy with methylprednisolone, were treated with rabbit anti-thymocyte globulin (ATG, Genzyme) at a dose of 1.5 mg/kg for 7–10 days, depending on the response. Acute humoral rejection was treated with plasmapheresis and postplasmapheresis intravenous immunoglobulin at 400 mg/kg daily for 5–7 days depending on the response. In refractory cases, further therapy with IV rituximab or bortezomib was used at clinician's discretion.

Statistical analysis

Standard descriptive statistics, including percentages and median (range) or mean ± standard deviation, were used to analyze the data, using SPSS for Windows, Version 16.0. (SPSS Inc. Released 2007. Chicago, SPSS Inc.). Kaplan–Meier analysis was used to generate the median allograft and patient survival.


  Results Top


Patients

Of 100 patients transplanted over 17 years, 77% were boys. The mean age of the cohort was 15.7 ± 2.3 years (median [range] 16 [5–18] years). [Table 1] lists the underlying causes of ESRD, which could not be determined in 48% of cases. Hemodialysis was the preferred modality of RRT, performed in 90 children; preemptive transplantation was performed in four patients.
Table 1: Etiology of end-stage renal disease

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Donors

All patients received grafts from living donors, chiefly parents, who comprised 91% of all donors; 2% donors were siblings and 7% remaining donors were other than related. Females donated twice as often as males (ratio 2:1). The median (range) age of donors was 43 (18–64) years.

Immunosuppression

Induction agents, administered to 50 patients, comprised interleukin-2 receptor blockers in 38 and ATG in 12 recipients. [Table 2] indicates that all patients were initiated on triple immunosuppression, and two-third of patients received therapy with prednisolone, tacrolimus, and MMF.
Table 2: Maintenance immunosuppression regimen

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Complications

Medical and surgical complications, observed during 72.5 (3–144) months of follow-up, are enumerated in [Table 3]. As shown, early postsurgical complications were seen in six patients, whereas allograft stenosis and hydronephrosis occurred in two and one cases, respectively, later. Serious infections were a major cause of morbidity. Urinary tract infection was the most common bacterial infection. Cytomegalovirus disease and hepatitis C virus infection were seen in five cases each. New-onset diabetes after transplant affected seven patients, whereas two developed the posttransplant lymphoproliferative disease.
Table 3: Complications after transplantation

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Allograft dysfunction

Fifty biopsies were performed for suspected AR in 35 patients. A diagnosis of AR was made in 26 episodes in the first 6 months following transplant [Table 4]. As shown in table, allograft function recovered in 19 of 26 AR occurring in the first 6 months, two of four cases during 6–12 months, and one of seven in cases diagnosed beyond 1 year of transplant. Other diagnosis based on biopsy included CNI toxicity (n = 5), chronic allograft nephropathy (n = 2), recurrence of glomerular disease (focal segmental glomerulosclerosis [FSGS] and membranoproliferative glomerulonephritis in two cases each), and de novo glomerular disease (FSGS in three cases; membranous nephropathy in one). Two patients underwent graft nephrectomy within 1 month of transplantation due to mucormycosis and graft artery aneurysm in one case each.
Table 4: Outcomes following episodes of allograft rejection

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Compliance

Compliance to immunosuppression was 95% at 1 year and 80% at 5 years after transplantation. Financial constraint was the most important factor associated with noncompliance.

Allograft and patient survival

During the median follow-up of 6 years, 15 patients were lost to follow-up. The rates of allograft survival at 1, 3, 5, and 10 years were 98%, 85%, 80%, and 73%, respectively [Figure 1]. Of 18 patients who progressed to ESRD, three patients underwent the second transplant. Causes of graft loss were chronic rejection (n = 8), acute vascular rejection (n = 3), recurrent disease (FSGS in 3 and membranoproliferative glomerulonephritis in 2), mucormycosis and acute vascular thrombosis (n = 1), and aneurysmal bleeding at anastomotic site (n = 1). Patients with episodes of AR had consistently lower rates of graft survival compared to that of recipients without AR [Figure 2].
Figure 1: Overall graft survival

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Figure 2: Graft survival of those with and without rejection episodes

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  Discussion Top


Kidney transplantation is the preferred management modality for children with ESRD but is still performed infrequently in developing countries. A questionnaire survey aimed at understanding the current practices in pediatric renal transplantation in India revealed the low incidence of undertaking pediatric transplants in children <6 years, chiefly due to the paucity of active cadaveric programs and lack of availability of trained pediatric nephrologists and staff.[6] The present study analyzed the long-term outcome of pediatric transplantation at a tertiary care center in a developing country considering the limitations.

According to the North American Pediatric Renal Transplant Co-operative Study (NAPRTCS) 2010 annual report, 53% of pediatric recipients were at or <12 years of age.[7] In contrast, the average age for our cohort was almost 16 years, similar to the age (14.9 ± 2.2 years) reported from Turkey.[8] The average age at transplantation was in adolescence in three series from north India,[5],[9],[10] indicating clearly that transplantation is performed in comparatively older children in our country. This difference may be attributed to the lack of access to appropriate and timely clinical care, as well as limitations of surgical and medical expertise. Contrasting with findings from NAPRTCS that indicate that girls constitute 41% of pediatric transplant recipients,[7] girls account for [5],[9],[10] Only four patients underwent transplantation preemptively in our series, as compared to a quarter of cases in the NAPRTCS registry.[7] The former probably reflects delayed care-seeking due to lack of awareness and financial constraints. Another noteworthy aspect of the data reported from the Indian subcontinent, including the present study, is the rarity of cadaveric renal transplantations, which comprise almost half the transplants for children in the NAPRCTS registry.[7] Most transplant recipients received grafts from first-degree relatives, with a predominance of parents, especially mothers, as donors. These findings, including average age at donation, are in concordance with data from the NAPRTCS registry[7] and other centers in India[5],[9],[10] and elsewhere.[11]

As shown in [Table 3] and [Table 5], the rates of postsurgical (immediate and delayed) complications and severe infections were similar to experiences at other centers in the country. Allograft survival in our cohort was estimated at 98% at 1 year and 80% at 5 years, similar to experience from the NAPRTCS that reported 1- and 5-year graft survival rates of 95.5% and 85.7% for patients receiving kidneys from living donors during 1995–2010.[7] However, the rates of allograft survival at 10-year follow-up in the present study are inferior to those reported by the NAPRTCS and even elsewhere within the country [Table 5], likely due to noncompliance to immunosuppressive therapy. While our attrition rate was high (15%), it is unlikely to have overestimated allograft survival as all had normal functioning graft at their last follow-up visit and the most common reason was change of center for follow-up to a nearby nephrologist. [Table 5] shows that our findings are comparable to those at two-tertiary care transplant experiences in the country.
Table 5: Results in the present study as compared to two studies from North India

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Executing an active and successful pediatric transplant program is challenging. Creation of successful models of a kidney transplant for the pediatric population, ensuring the availability of less-expensive immunosuppressive agents, establishing adequate transplant centers dedicated to the pediatric age group, and a successful cadaveric program to provide kidneys to these patients at the appropriate time will be useful in enabling the success of such a program. Apart from an active initiative from the medical fraternity, participation of government and other agencies with optimal funding support is highly desirable as an initial step to achieve this goal.


  Conclusions Top


Pediatric renal transplantation at our center in India was predominantly performed in adolescent boys with parents as donors. The rates of 1- and 5-year allograft survival were satisfactory, but the 10-year graft survival was inferior as compared with other centers. Social awareness, promotion of cadaveric donation, stressing on drug adherence, and posttransplant socioeconomic support should improve the long-term graft survival rates.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
McDonald RA, Watkins SL. Progress in renal transplantation for children. Adv Ren Replace Ther 1996;3:60-8.  Back to cited text no. 1
    
2.
Haberal M, Arda IS, Karakayali H, Emiroǧlu R, Bilgin N, Aslan G, et al. Renal transplantation in children. Transplant Proc 2000;32:520-1.  Back to cited text no. 2
    
3.
Furth SL, Gerson AC, Neu AM, Fivush BA. The impact of dialysis and transplantation on children. Adv Ren Replace Ther 2001;8:206-13.  Back to cited text no. 3
    
4.
Rodrigo E, Ruiz JC, Piñera C, Fernández-Fresnedo G, Escallada R, Palomar R, et al. Creatinine reduction ratio on post-transplant day two as criterion in defining delayed graft function. Am J Transplant 2004;4:1163-9.  Back to cited text no. 4
    
5.
Gulati S, Kumar A, Sharma RK, Gupta A, Bhandari M, Kumar A, et al. Outcome of pediatric renal transplants in a developing country. Pediatr Nephrol 2004;19:96-100.  Back to cited text no. 5
    
6.
Sethi SK, Sinha R, Rohatgi S, Kher V, Iyengar A, Bagga A. Pediatric renal transplant practices in India. Pediatr Transplant 2017;21:e12892.  Back to cited text no. 6
    
7.
The 2010 Annual Report of the North American Renal Transplant Cooperative Study. Available from: http://www.naprtcs.org. [Last accessed on 2019 Feb 15].  Back to cited text no. 7
    
8.
Emiroglu R, Moray G, Sevmis S, Sözen MH, Bilgin N, Haberal M. Long-term results of pediatric kidney transplantation at one center in Turkey. Transplant Proc 2005;37:2951-3.  Back to cited text no. 8
    
9.
Srivastava A, Prabhakaran S, Sureka SK, Kapoor R, Kumar A, Sharma RK, et al. The challenges and outcomes of living donor kidney transplantation in pediatric and adolescent age group in a developing country: A critical analysis from a single center of North India. Indian J Urol 2015;31:33-7.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Meena J, Sinha A, Hari P, Dinda AK, Khandelwal P, Goswami S, et al. Pediatric kidney transplantation: Experience over two decades. Asian J Pediatr Nephrol 2018;1:22-8.  Back to cited text no. 10
  [Full text]  
11.
Mehrabi A, Kashfi A, Tönshoff B, Feneberg R, Mehls O, Schemmer P, et al. Long-term results of paediatric kidney transplantation at the University of Heidelberg: A 35 year single-centre experience. Nephrol Dial Transplant 2004;19 Suppl 4:iv69-74.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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