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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
RENAL DATA FROM ASIA–AFRICA  
Year : 2020  |  Volume : 31  |  Issue : 2  |  Page : 482-492
Ten-year appraisal of pediatric renal allograft biopsies: Points to ponder


1 Department of Pathology, Lab Medicine, Transfusion Services and Immunohematology; Department of Stem Cell Therapy and Regenerative Medicine, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H. L. Trivedi Institute of Transplantation Sciences, Civil Hospital Campus, Ahmedabad, Gujarat, India
2 Department of Pathology, Lab Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H. L. Trivedi Institute of Transplantation Sciences, Civil Hospital Campus, Ahmedabad, Gujarat, India
3 Department of Biostatistics, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H. L. Trivedi Institute of Transplantation Sciences, Civil Hospital Campus, Ahmedabad, Gujarat, India

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Date of Submission19-Jul-2019
Date of Decision29-Aug-2019
Date of Acceptance29-Sep-2019
Date of Web Publication09-May-2020
 

   Abstract 


There is paucity of literature on pediatric renal allograft biopsy (RAB) evaluation. We present RAB findings of pediatric renal transplantation (RT) and correlate with outcome. This is a 10-year retrospective study of diagnostic RAB of children <12 years divided in to three groups: Group 1 (n = 9): less than haplo-match living donor RT (LDRT), Group 2 (n = 32): greater than or equal to haplo-match LDRT, and Group 3 (n = 7): deceased donor RT. Demographics, biopsy findings, survival, and serum creatinine (SCr) were evaluated. Statistical analysis was performed using IBM SPSS Statistics version 20.0. The most common findings were antibody-mediated rejection (ABMR) observed in 77.7%, 45%, and 71.5% and T-cell-mediated rejections (TCMRs) in 33.3%, 52.5%, and 42.9% in Groups 1, 2, and 3, respectively. Recurrent oxalosis was seen in 5% in Group 2. Death-censored graft survival was 100% at 1 year and 43.8% from 5 to 9 years in Group 1; 93.5%, 76.6%, 56.5%, and 14.4% at 1, 5, 10, and 15 years in Group 2; 100% at one year; and 71.4% from 5 to 12 years in Group 3. No patient appeared after 9 years in Group 1 and after 12 years in Group 3. In Group 1, the mean SCr (mg/dL) was 1.06 ± 0.45, 2.12 ± 1.87, and 1.39 at 1, 5, and 9 years; 1.35 ± 0.97, 1.73 ± 1.15, and 2.49 ± 1.64 in Group 2; and 1.15 ± 1.24, 1.43 ± 0.1, and 1.18 ± 0.06, respectively, in Group 3 at 1, 5, and 10 years posttransplant. ABMR followed by TCMR was the most common injury in all the groups. Group 1 had more rejections than others.

How to cite this article:
Vanikar AV, Nigam LA, Kanodia KV, Patel RD, Suthar KS, Mehta AH. Ten-year appraisal of pediatric renal allograft biopsies: Points to ponder. Saudi J Kidney Dis Transpl 2020;31:482-92

How to cite this URL:
Vanikar AV, Nigam LA, Kanodia KV, Patel RD, Suthar KS, Mehta AH. Ten-year appraisal of pediatric renal allograft biopsies: Points to ponder. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2020 Jul 13];31:482-92. Available from: http://www.sjkdt.org/text.asp?2020/31/2/482/284024



   Introduction Top


Peritoneal dialysis or hemodialysis for children suffering from end-stage renal disease (ESRD) are acceptable bridging modalities till renal transplantation (RT) is available for them.[1] Difficulties in vascular access due to smaller diameter of vessels, high chances of infections, and other comorbid complications related to the procedure of dialysis, along with growth retardation, were the major hurdles in providing good quality of life to children with ESRD.[2],[3] Transplantation has emerged as the best choice for improving the quality of life in these children.[1] The major problems with pe- diatric RT, especially in developing countries, were lack of awareness about RT, financial resources, recurrence of original disease, organ availability, and, if available, donor-recipient size disparity, relatively poor survival rates, and noncompliance to immunosuppressive medications.[4] Hence, transplantation in children did not pick up universally as compared to transplantation in adults.[5] Pediatric RT picked up in the eighties in developed nations; in developing nations, the graph is improving gradually.[6],[7] In Saudi Arabia, pediatric RT constituted 26 (17.9%) out of 145 deceased donor RT (DDRT) in the year 2017.[8] Graft survival at one of the Indian centers was reported as 91.1% at 1 year, 80.4% at 5 years, and 75.1% at 10 years.[6] Overall 5-year transplant survival rates have been reported between 44% and 95% and between 23% and 95% at 10 years by different centers from the UK, South Africa, the Netherlands, Germany, Pakistan, Belgium, Turkey, Iran, the USA, and Spain.[2],[7],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24] One of the best modalities to evaluate the graft function and predict long- term outcome would be a renal allograft biopsy (RAB). Surveillance biopsies are ideal to detect early subclinical rejections.[25] However, the risk of gross hematuria due to larger needle bore (16G versus 18G), risk of penetrating medulla with inflamed arteries, and compliance are major challenges in pediatric patients.[25],[26] Diagnostic biopsies are an important tool for the management of pediatric RT with graft dysfunction, but the procedure is little difficult in children due to their non- cooperation, requiring sedation or even anesthesia for performing a biopsy.[26] Rejections and recurrence are the common findings in diagnostic biopsies.[26] The incidence of antibody-mediated rejections (ABMRs) decreases with better human leukocyte antigen (HLA) matching, hence it is universally accepted as an important prognosticator for the outcome of RT.[27],[28] However, in children, because thymus is active as compared to adults and the immune system is still evolving, T- cell-mediated rejections (TCMRs) are believed to be predominant rather than ABMR. Hence, very encouraging long-term results of RT in children have been observed as compared to adults.[5],[29],[30]

We carried out this institutional ethics committee-approved retrospective observational study of pediatric RAB and compared the outcome in living donor RT (LDRT) (with respect to HLA match) and DDRT in young children.


   Materials and Methods Top


Study design

This was a single-center, 10-year retrospective analysis of indicated RABs performed from 2008 to 2017. Patients aged < 12 years at the time of transplantation and who had undergone at least one diagnostic RAB were included in the study.

All the biopsies were compared for mean posttransplant and mean follow-up time period. Serum creatinine (SCr) (mg/dL) levels at the time of biopsy and at follow-up were compared.

Outcome

Death-censored graft loss was determined by the time between the date of transplantation and date of graft failure indicated by need for dialysis, date of death, or last date of follow- up with a functioning graft. Patient death and dialysis dependency were the proposed end points of this study.

The biopsies were divided into three groups: Group 1 consisted of LDRT with HLA less than haplo-match (3/6), Group 2 consisted of LDRT with HLA greater than or equal to haplo-match, and Group 3 consisted of DDRT. HLA match was evaluated for A, B, and C for Class I and DP, DQ, and DR for Class II antigens. Haplo-identical donors were defined as those who matched exactly half of their HLA with the recipients. Donor-recipient demographics evaluated included recipient age, sex, etiology of ESRD, donor age, sex, relationship, and HLA match. The outcome was evaluated in terms of SCr for graft function, biopsy findings, and graft survival. All the patients had received triple immunosup- pression comprising of tacrolimus, mycofeno- late, and prednisone and anti-rejection therapy as per the standard practice. HLA matching was carried out as per standard American Society for Histocompatibility guidelines, and antibodies were measured using Luminex platform (CPC Diagnostis Pvt. Ltd, India) for single-bead assay.

Slides were prepared as per standard lab practices on formalin-fixed needle biopsy bits for light microscopy and C4d immune- histochemistry as per manufacturer’s protocol. Hematoxylin and eosin, Gomori’s trichrome, periodic acid-Schiff, and Jone’s silver methe- namine stains were used on 3-ęm-thick sections. C4d staining was performed using“Novolink™ Polymer Detection System” (Leica Biosystems, Germany) with rabbit anti- human C4d monoclonal antibody (clone SP91, Spring Bioscience, USA) and Novolink™ Polymer Anti-rabbit Poly-HRP-IgG. A panel of five pathologists independently reported, and consensus diagnosis generated was finally reported as per the modified Banff 2015 guide- lines.[31],[32] Membranous/lupus nephropathy slides were used as positive controls. Endothelial cells lining the medium caliber blood vessels were taken as internal control.

Intensity of rejections was scored as <ag1at1av0ai1, ≥ag1at1av0ai1 for activity and <cg1ct1cv0ci1, and ≥cg1ct1cv0ci1 for chro- nicity. Peritubular capillaritis (PTC) score, calcineurin inhibitor toxicity (CNIT), and other findings were also recorded.


   Statistical Analysis Top


Statistical analysis was performed using IBM SPSS statistics version 20.0 (IBM Corp., Armonk, NY, USA). One-way ANOVA test for parametric distribution and Kruskal-Wallis test for nonparametric test were used for comparison. Categorical data were compared using Chi-square tests or Fisher’s exact tests. Kaplan-Meier curves and log-rank tests were used to describe and compare death-censored graft survival rates. Cox regression analysis was performed for carrying out hazard ratio (HR). Independent /-tests were used for the comparison of two groups. P <0.05 was considered statistically significant.


   Results Top


Demographics [Table 1]
Table 1: Demographics of pediatric renal transplants divided into three groups

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Group 1 enrolled nine patients which comprised seven males and two females, with a mean age of 10.1 ± 2.5 years and mean HLA- match of 1.1 ± 0.9. All patients had undergone a single biopsy. Donors were mainly grandparents with a mean age of 45.1 ± 9.5 years. The most common etiologies of ESRD were reflux nephropathy in 44.4% and dysplastic kidneys in 33.3% of the patients.

Group 2 enrolled 32 patients that comprised 30 males and 2 females, with a mean age of 10.2 ± 1.9 years and a mean HLA-match of 3.2 ± 0.50. One patient had undergone three biopsies, six had undergone two biopsies, and 25 had undergone a single biopsy. Donors were parents n = 30) and grandparents (n = 2) with a mean age of 39.8 ± 4.5 years. Reflux nephropathy was observed in 25% of patients, and was the most common etiology for ESRD followed by unknown etiology in 18.8% of the patients.

Group 3 enrolled seven patients which comprised six males and one female, with a mean age of 9.6 ± 1 years. The mean HLA- match performed in three patients was 0.7 ± 0.6. All patients had undergone a single biopsy procedure. The mean age of deceased donors was 35.3 ± 12.9 years. The most common etiologies of ESRD were reflux nephropathy and dysplastic kidneys, each constituting 28.6% of patients.

Mean SCr at the time of biopsy was 2.50 ± 0.02 mg/dL in Group 1, 3.75 ± 0.55 mg/dL in Group 2, and 2.19 ± 0.83 mg/dL in Group 3. There was no statistically significant difference among the three groups.

Biopsy findings [Table 2]a and [Table 2]b


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The mean posttransplant biopsy period was 32.5 ± 35.5 months in Group 1. Out of the nine biopsies evaluated, the major findings were acute ABMR in 44.4% of biopsies and acute TCMR in 33.3% of biopsies. In ABMR cases, TCMR was noted in two out of four, and CNIT in one; chronic active ABMR was found in 33.3% (n = 3) biopsies, with one of them having combined CNIT and other having TCMR along with CNIT. Acute borderline TCMR +CNIT and BKV nephropathy (BKVN) with de novo collapsing glomerulopathy (CG) were found in one biopsy each. Activity score ≥ag1at1av0ai1 was observed in 75% and score <ag1at1av0ai1 was observed in 25% of biopsies. Chronicity score ≥cg1ct1cv0ci1 was observed in 66.7% and score < cg1ct1cv0ci1 was observed in 33.3% of biopsies. C4d score-3 was observed in 57.1%, C4d score-2 in 28.6%, C4d score-1 in 14.3%, and C4d score 0 was not seen in any biopsy. PTC score ≥1 was observed in 42.9% and PTC score <1 was observed in 57.1% of biopsies.

The mean posttransplant biopsy period was 40.7 ± 53.2 months in Group 2. Out of forty biopsies evaluated, the major findings were acute ABMR in 25% (n = 10) of biopsies and acute TCMR in 22.5% of biopsies. In acute ABMR biopsies, combined borderline TCMR was found in one out of 10, TCMR in five out of 10, CNIT in one out of 10, and combined TCMR as well as CNIT in one out of 10 biopsies. Chronic active ABMR was observed in 30% (n = 12) of biopsies, with combined TCMR in eight out of 12, combined CNIT in one out of 12, and both TCMR and CNIT in three out of 12 biopsies. Acute TCMR was noted in one biopsy and borderline TCMR in two biopsies. Interstitial fibrosis with tubular atrophy of unexplained etiology (IF/TA) was observed in two biopsies, and acute tubular necrosis (ATN) in three biopsies. Posttrans- plant lymphoproliferative disorder (PTLD) was found in one biopsy. Oxalosis was seen in two biopsies. Acute tubulo-interstitial nephritis (ATIN) was observed in two biopsies: one in case of ESRD secondary to reflux nephropathy and other with obstructive uropathy. The patient with reflux nephropathy had recurrence of ATIN on repeat biopsy. Two biopsies had unremarkable morphology. Two biopsies revealed acute-on chronic CNIT with CG, and one of them also had changes of thrombotic microangiopathy (TMA). Activity score ≥ag1at1av0ai1 was observed in 72.7% and score <ag1at1av0ai1 was observed in 27.3% of biopsies. Chronicity score ≥cg1ct1cv0ci1 was observed in 8.3% and score <cg1ct1cv0ci1 were observed in 91.6% of biopsies. C4d score-3 was observed in 31.8%, C4d score-2 in 22.7%, C4d score-1 in 31.8%, and C4d score-0 in 13.7% of biopsies. PTC score ≥1 was observed in 22.7% and PTC score <1 was observed in 77.3% of biopsies.

The mean posttransplant biopsy period was 23.9 ± 18.9 months in Group 3. Out of seven biopsies, the major findings were chronic active ABMR in 42.9% and acute ABMR and chronic TCMR each in 28.6% biopsies. Out of the two acute ABMR, combined acute ABMR with TCMR was found in one biopsy; out of three chronic active ABMR, two had combined TCMR and one had CNIT. Other findings were ATIN in one and BKVN (Stage A) in one biopsy. Activity score ≥ag1at1av0ai1 was observed in 20% and score <ag1at1av0ai1 was observed in 80% of biopsies. Chronicity score ≥cg1ct1cv0ci1 was observed in 66.7% and score <cg1ct1cv0ci1 was observed in 33.3% of biopsies. C4d score-3 was observed in 40%, C4d score-2 in 20%, C4d score-1 in 40% biopsies and C4d score-0 in none of the biopsies. PTC score ≥1 was observed in 20% and PTC score <1 was observed in 80% of biopsies. Interesting histopathology findings are depicted in [Figure 1].
Figure 1: Histopathology findings: Top left; (A1) A 11-year-old male with end-stage renal disease induced by dysplastic kidneys underwent deceased donor renal transplantation from a 50-year-old man with brain death following road traffic accident, who developed acute graft dysfunction at 5 months posttransplant with rise in serum creatinine from 0.89 to 1.68 mg/dL. Renal allograft biopsy performed. (A1) two glomeruli with surrounding tubules. Both glomeruli show mild mesangial prominence, fairl open capillaries infiltrated by few leukocytes and lined by membranes of normal thickness, tubules show moderate degeneration with mild tubulitis and focal isometric vacuolization and peritubular capillaries showing dilated lumina infiltrated by 2–5 leukocytes, H and E, ×200; at the center (A2) diffuse C4d deposits across peritubular capillaritis, C4d stain, ×200; and on extreme right (A3) showing SV40- positive nuclei in tubular epithelial cells, SV40 antigen, ×100.
Middle panel: A 15-year-old boy with nephrocalcinosis transplanted with HLA 3/6 match mother's (33 years old) kidney developed gradual rise in serum creatinine from baseline of 0.79 mg/dL to 3.16 mg/dL at 7 months posttransplant along with mild hematuria. (B1) Renal allograft biopsy showing on left several tubular lumina filled with birefringent fan-shaped or hexagonal crystals with broad ends embedded in tubular membranes, scattered mononuclear cellular infiltrates in parenchyma and occasional mild tubulitis also evident, H and E, ×200; (B2) on right panel polarizer depicting crystals in tubular lumina, ×200.
Lower panel: A 13-year-old boy with reflux nephropathy underwent renal transplantation with HLA 3/6 match father's (41-year-old) kidney and presented with rise in serum creatinine from baseline of 1.01 to 1.41 mg/dL at 81 days posttransplant along with proteinuria (urine albumin 500 mg/dL). Biopsy was performed. On left (C1) two glomeruli with surrounding tubules, glomerulus on top shows mild glomerulitis and glomerulus below shows aneurysmally dilated lumina filled with hyaline thrombi, focal mesangiolysis, and rarely duplicated membranes, tubules show mild degeneration, tubulitis, and proteinaceous casts, and peritubular capillaritis lumina infiltrated by 2–3 leukocytes, H and E stain, ×200; (C2) in middle panel, Gomori's trichrome stain showing fuchsinophilic deposits and fragmented red blood cells in aneurysmally dilated glomerular capillaries, ×400, on extreme right, (D) are seen two glomeruli with surrounding tubules, both glomeruli have variably shrunken capillary tufts surrounded by proliferating podocytes, showing features of collapsing glomerulopathy, Jone's silver methenamine stain, ×200.
(in brief – histopathology findings: top; antibody-mediated rejection with thrombotic microangiopathy and BKV nephropathy; H and E, C4d stains, ×200 SV 40 antigen stain, ×100. Middle: nephrocalcinosis posttransplant H and E, ×200; (b2) polarizer depicting crystals in tubular lumina, ×200. Lower panel: Collapsing glomerulopathy with thrombotic microangiopathy, H and E stain, Gomori's trichrome, Jone's silver methenamine stains, ×200).


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Graft function and survival [Table 3]
Table 3: Graft function in terms of serum creatinine (in mg/dL) in the three groups.

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Group 1 completed 9 years of study with a mean SCr (mg/dL) of 1.06 ± 0.45, 2.12 ± 1.87, and 1.39 at 1, 5, and 9 years posttransplant, respectively. At 1, 5, and 10 years post- transplant, the mean SCr (mg/dL) in Group 2 was 1.35 ± 0.97, 1.73 ± 1.15, and 2.49 ± 1.64, respectively. In Group 3, the mean SCr (mg/dL) was 1.15 ± 1.24, 1.43 ± 0.10, and 1.18 ± 0.06, respectively, at 1, 5, and 10 years posttransplant. There was no statistically significant difference between the three groups all across except at 10 years posttransplant when Group 3 had better function than Group 2 (P = 0.04).

Graft survival

At 1 year posttransplant, graft survival was 100% in Group 1 and Group 3 and 93.5% in Group 2 [Figure 2]. At five years post- transplant, the graft survival was 43.8% in Group 1, 76.6% in Group 2, and 71.4% in Group 3. Group 1 finished nine years post- transplant with a graft survival of 43.8%. Graft survival was 56.5% at 10 years in Group 2 and 71.4% in Group 3. There was no statistically significant difference between the groups P = 0.48). Graft loss was associated with higher chronicity scoring, recurrence of oxalosis, PTLD, TMA, and CG.
Figure 2: Kaplan–Meier graft survival plot of the three groups.

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Overall comparison of the three groups

Cox regression analysis showed that the risk for ABMR in Group 1 was more as compared with Group 2 with a HR of 1.53, [confidence interval (CI) (0.642, 3.648)] with P = 0.34. While comparing Group 1 with Group 3, the risk for ABMR was less in the former [HR = 0.70, CI (0.202, 2.451), P = 0.58). While comparing Group 2 with Group 3, the risk for ABMR was less in the former [HR = 0.59, CI (0.219, 1.607), P = 0.31).

For TCMR, the risk in Group 1 was slightly less as compared with Group 2, i.e., HR = 0.96,CI (0.322, 2.858) with P = 0.94. The risk in Group 1 was slightly less as compared with Group 3, i.e., HR = 0.92, CI (0.203, 4.186) with P = 0.92. The risk in Group 2 was slightly less as compared with Group 3, i.e., HR = 0.94, CI (0.274, 3.208) with P = 0.92.

For CNIT, the risk in Group 1 was more as compared with Group 2, i.e., HR = 2.60, CI (0.731, 9.261) with P = 0.14. The risk in Group 1 was more as compared with Group 3, 1. e., HR = 1.56, CI (0.161, 15.089) with P = 0.70. The risk in Group 2 was less as compared with Group 3, i.e., HR = 0.71, CI (0.083, 6.136) with P = 0.76.

Thus, ABMR was the predominant finding followed by TCMR in all groups, however the incidence was more with Group 1 where donors were less than haplo-match. ABMR and TCMR were highest in Group 1 with poor donor-recipient HLA match, as compared to other two groups. CNIT was highest in Grou Recurrent oxalosis and CNIT-induced TMA and CG were also significant findings in Group 2, leading to poor outcome. Overall graft function and survival were best in Group 3 followed by Group 2 and Group 1.


   Discussion Top


According to a published study, children with ESRD are underprivileged as compared to their healthy counterparts.[33] They suffer from psychological stress, leading to the risk of poor academic performance, and are often struggling socially, with their fluid and dietary regimes in addition to the life cycle of recurrent dialysis.[34] The common causes of ESRD in children are congenital malformation/inherited disorders such as renal dysplasia, obstructive uropathy, and glomerular diseases such as focal segmental glomerulo- sclerosis (FSGS) and IgA nephropathy.[29],[34]

The exact incidence and burden of CKD in children is not known in Egypt, however chronic interstitial nephritis, diffuse sclerosis with tubular atrophy, nephronophthisis, and tubular necrosis suggestive of pyelonephritis together constituted the common causes of chronic renal failure in a study by Abdel- Hafez et al.[34],[35],[36] In a study by Ahmed et al from Mansoura center in Egypt, chronic GN comprised 19.5% and chronic interstitial nephritis comprised 11.5% of burden of CKD in pediatric patients.[37] However, the age limit in their study was 18 years with mean patient age of 13.7 years. McEnery et al in 1992 in North American Pediatric Renal Transplant Cooperative (NAPRTC) study of 1150 patients aged <17 years reported 42% of congenital malformation, 12% of FSGS, and 46% other reasons as common causes of ESRD.[29] Our study also has comparable findings with 70% of patients having ESRD secondary to congenital or inherited disorders and about 14% having ESRD secondary to acquired glomerular diseases. All these studies have included patients up to 17 years of age, whereas we have included young children up to 12 years of age because the current pediatric practice guidelines have set the age of 12 35 years.

The NAPRTC study reported DDRT as the common transplant modality (57%) as compared to LDRT (43%).[29] Our observations also are in concurrence with this studv. In a study by Sinha et al from North India, RT patients were in the age ranging from 3.8 to 18 years (mean age: 13.3 ± 4 years), among which 91% of transplants were LDRT, which is in concordance with our study where majority of donors were living related.[6]

It has been established by Terasaki and Ozawa and confirmed by Ruffino et al that antibodies are associated with adverse effect on graft function.[27],[28] We have also observed in the current study that graft survival of non- haplo-identical LDRT was low (43.8%) as compared to the graft survival of 76.6% in haplo-identical LDRT and 71.4% in DDRT at 5 years. Five- and 10-year actuarial patient survival in the study by Ahmed et al was 91.6 ± 1.74% and 81.63 ± 2.92% and the corres-ponding graft survival was 83.9 ± 2.28% and 58.34 ± 3.53%, respectively, and 50% of their transplants were haplo-identical.[37] Interestingly, our study shows a better graft survival in DDRT of 100% at one year and 71.4% thereafter till 12 years, which is superior to the other groups. Unfortunately, in Group 2 with haplo-identical RT in the current study, graft loss was observed due to recurrence of oxalosis in two patients and severe form of CNIT and IF/TA in two patients each. This also confirms the belief that long-term use of CNI induces irreversible changes eventually in almost all cases by 10 years of transplantation transplantation as observed by Ahmed et al, Nankivell et al and Naesens et al.[37],[38],[39]

Isiyel et al from Turkey in their 15 years study of 52 RT biopsies reported the most common findings as acute TCMR in 11.6% of biopsies followed by chronic allograft nephro- pathy and ATN, in 4% each, and ABMR in 1.5% of biopsies.[26] Ahmed et al reported acute cellular rejection in 34.9%, vascular rejection in 3.7%, and chronic rejection in 20.1% of their total 338 pediatric transplants.[37] In a Canadian study by Dart et al on 240 pediatric protocol RABs during the first five years posttransplant, chronic tubulo-interstitial injury was observed in the 1st year of transplant, whereas chronic vascular injury and glomerulosclerosis were more apparent at 2536 months posttransplant and thereafter.[40] These authors opined that attempts to reduce CNI exposure should be made before 2 years of transplantation.

Our study revealed high incidence of ABMR (77.7%) in LDRT with less than haplo-match followed by DDRT (71.5%), and then in LDRT (45%) with greater than haplo-match donors. It also suggests that ABMR is an equally confounding risk factor in pediatric population similar to adults. In addition, biopsy findings revealed recurrence of oxalosis, which is known to cause graft loss if RT is carried out without simultaneous liver transplantation. Similarly, severe form of CNIT also was responsible for graft loss.

The limitation of the study is that the data of mean dialysis procedures and transfusions received were not available.

To conclude, this 10-year study of pediatric RABs shows promising results for pediatric RT. The incidence of ABMR is highest with nonhaplo-identical donors than haplo-identical LDRT in young children. TCMR is the second common cause of graft dysfunction. Recurrence of oxalosis and severe form of CNIT can be harbingers of poor outcome. CNIT in graft biopsy should caution for weaning over from CNI. DDRT appears to be a preferred option for RT in children up to 12 years of age.


   Acknowledgments Top


We are grateful to the patients and their parents and guardians for allowing us to study the biopsies, and to the I/C Director, Dr. Vineet Mishra, for granting permission to publish the data of this observational study. Our physician colleagues including Departments of Anesthesia and Critical Care, Pediatric Nephrology and Transplant Medicine, Urology and Transplant Surgery, Radiology, Transplant Coordinators, nursing staff, and all lab staff deserve special thanks for their respective role in surgery, patient care, communication, and testing, thereby providing support in completing this work successfully.

Conflict of interest: None declared.



 
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Correspondence Address:
Aruna V Vanikar
Department of Pathology, Lab Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H. L. Trivedi Institute of Transplantation Sciences, Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
India
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DOI: 10.4103/1319-2442.284024

PMID: 32394922

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