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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 6  |  Page : 1331-1343
Thrombotic microangiopathy in a renal allograft: Single-center five-year experience

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-Medicity Campus, Asarwa, Ahmedabad, 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-Medicity Campus, Asarwa, Ahmedabad, India
3 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-Medicity Campus, Asarwa, Ahmedabad, India
4 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-Medicity Campus, Asarwa, Ahmedabad, India

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Date of Web Publication29-Jan-2021


Thrombotic microangiopathy (TMA) is devastating for renal transplantation (RT) causing graft/ patient loss. We present 5-year experience of TMA in RT in retrospective study of indicated renal allograft biopsies with TMA. Patient–donor demographics and associated histological findings with respect to transplants under tolerance induction protocol (Group 1) were compared with patients transplanted under triple immunosuppression (Group 2). Statistical analysis was performed using IBM SPSS Statistics version 20. Sixty-one (4.1%) of 1520 biopsies [Group 1:17 (1.9%)/882, Group 2:44 (6.9%)/638] revealed TMA. Tacrolimus trough levels were normal. There was no evidence of systemic involvement in any patient. Mean age was 36.8 years with 70.6% males, HLA-match, 2.6/6, and the most common original disease unknown (41.2%) in Group 1, and 35.9 years with 86.4% males, HLA-match, 2.1/6, and the most common original disease unknown (50%) in Group 2. Biopsies were performed at mean 5.1-year posttransplant in Group 1 and 2.3 years in Group 2. Acute TMA constituted 47% Group 1 and 43.2% Group 2 biopsies; of these, antibody-mediated rejections were observed in 58.8%, T-cell mediated rejections in 11.8%, tacrolimus toxicity in 76.5%, and other findings in 35.3% Group 1; and 61.4%, 25%, 50%, and 18.2%, respectively, in Group 2 biopsies. Higher rejection activity scores were more in Group 2. Postbiopsy 1- and 5- year patient survival was 94.1%, 86.9% in Group 1 and 92.1%, 88.3% in Group 2; 1- and 4-year graft survival was 52.9%, 15.9% in Group 1 and 20.3%, 5.4% in Group 2. TMA was poor prognosticator for RT, especially under triple immunosuppression. Antibody- mediated rejection and tacrolimus toxicity were more prone to TMA.

How to cite this article:
Vanikar AV, Kanodia KV, Suthar KS, Nigam LA, Patel RD, Thakkar UG, Mehta AH. Thrombotic microangiopathy in a renal allograft: Single-center five-year experience. Saudi J Kidney Dis Transpl 2020;31:1331-43

How to cite this URL:
Vanikar AV, Kanodia KV, Suthar KS, Nigam LA, Patel RD, Thakkar UG, Mehta AH. Thrombotic microangiopathy in a renal allograft: Single-center five-year experience. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2021 Jun 25];31:1331-43. Available from: https://www.sjkdt.org/text.asp?2020/31/6/1331/308342

   Introduction Top

Renal transplantation (RT) is now a well-accepted therapeutic modality for patients with end-stage renal disease (ESRD), however certain diseases such as atypical hemolytic uremic syndrome (aHUS) are known to recur after RT.[1] Thrombotic microangiopathy (TMA) may also occur for the first time after RT in some patients most commonly in association with antibody-mediated rejection (ABMR) or calcineurin inhibitor toxicity (CNIT).[1] Whatever the cause, once TMA is observed in a renal allograft biopsy (RAB), it ensues bad news for the patient as well as the treating physician because the chances of improving outcome, especially in terms of graft function and survival are dismal.[1] TMA is a lesion of the blood vessel walls, mainly displaying thickening of the small and medium caliber vessel walls and intraluminal plugging with platelet/RBC/fibrin thrombi, eventually causing obstruction of the vessel lumina.[2],[3] It has predilection for kidney and brain, followed by involvement of other organs. Investigative panel shows consumptive thrombocytopenia and microangiopathic hemolytic anemia (MAHA). The clinical entity with predominance of renal lesions is called HUS and if there is predominance of brain or neural involvement, the entity is named as thrombotic thrombocytopenic purpura (TTP).[2] HUS is rare. Formerly, when it was caused by infections with Shiga-like toxin-producing strains of Escherichia coli (STEC), it was called typical HUS or STEC-HUS and when unrelated to infections, it was called aHUS.[4] Unlike the former which usually recovers with conservative management and control of infection, the later has poor prognosis and often progresses to ESRD.[4] One of the major abnormalities in aHUS is caused by disturbance in the alternative pathway of complement activation.[4]

We carried out a retrospective study of RABs performed in our center with the aim of evaluating the incidence of TMA in RAB and their effect on outcome of RT. The goal of this study was to establish the most common cause of TMA in RAB and indicate the guidelines to minimize or prevent TMA in renal allograft.

   Material and Methods Top

Study design

This was a single-center 5-year retrospective analysis of indicated RABs performed from 2014 to 2018. All the biopsies which were adequate as per the Banff criteria and which displayed the histological criteria for TMA were included in the study.[4],[5],[6] Biopsies displaying pathologies other than TMA were excluded from the study. Diagnosis of systemic involvement of TMA was made if lab investigations revealed hemolytic anemia with the presence of schistocytes with/without normoblasts, thrombocytopenia (platelet count <1.5 × 105/μL, presence of giant platelets in peripheral smear, associated reticulocytosis, elevated serum lactic dehydrogenase, elevated indirect bilirubin, and free hemoglobin in urine/blood along with normal coagulation profile and negative Coomb’s test. Serum creatinine (SCr) for renal involvement was also noted.

The biopsies were divided into two main groups, Group 1 biopsies comprised patients who had undergone tolerance induction protocol (TIP) using pretransplant stem cell therapy (SCT) with donor cells, and Group 2 consisted of patients who had opted out of TIP and who were transplanted under the standard calcineurin inhibitor (CNI)-based triple immunosuppression.

Minimization of Immunosuppression

Patients in Group 1 subjected to TIP, with stable graft function without rejection underwent minimization by prednisone (5–10 mg/ day or on alternate days) after 1st month of transplantation. Patients with a single acute rejection episode who responded to standard treatment or who had stable graft function were treated with two immunosuppressants – prednisone (5–10 mg/day) and CNI [cyclos-porine (CsA) (05 mg/kg BW/d)/tacrolimus (0.02 mg/kg BW/day)] or sirolimus (1 mg at night) or Mycofenolate (360 mg/day) or azathioprine (50 mg/d). Mycofenolate or aza-thioprine was preferred over the CNI after 6 months of stable graft function. For repeated/ resistant rejections, patients were subjected to three drug immunosuppression regimen; pred-nisone (5–10 mg/ day), CNI/sirolimus, and azathioprine/MMF, all in the low doses mentioned above. Group 2 patients under standard triple immunosuppression were receiving prednisone (5-10 mg/day), tacrolimus, 0.05 to 0.08 mg/kgBW/day or sirolimus, and myco-fenolate 360 mg three or four times a day.[7]

Patient–donor demographics, graft function in terms of SCr at the time of biopsy, tacrolimus trough levels, biopsy findings associated with TMA, and outcome were compared for mean posttransplant and mean follow-up time period in years. Donor–recipient demographics evaluated included recipient age, sex, etiology of ESRD, donor relationship, and HLA match. Outcome was evaluated in terms of SCr for graft function, biopsy findings, graft survival, and patient survival. HLA-match was evaluated for 6 loci, A, B, and C for Class I, and DP, DQ, and DR for Class II antigens. SCr (mg/dL) levels at the time of biopsy and every year after RT were compared.


Patient and death-censored graft survival were determined by time between date of biopsy and either 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.

Reporting of renal allograft biopsy

A panel of five pathologists independently reported, and consensus diagnosis generated was finally reported as per modified Banff 2017 guidelines [Table 1].[5],[6] Formalin-fixed biopsy specimens were processed for light microscopy, and C4d immunohistochemistry as per manufacturer’s protocol. For light microscopy, 3 μm thick sections were stained with hematoxylin and eosin, Gomori’s trichrome, periodic acid, Schiff and Jones silver methaneamine stains. The C4d staining was performed on 3 μm thick paraffin sections using “Novolink™ Polymer Detection System” (Leica Biosystems, Germany) with rabbit antihuman C4d monoclonal antibody (clone SP91, Spring Bioscience, USA) and NovolinkTM Polymer antirabbit Poly-HRP-IgG. 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 chronicity. Peritubular capillaritis (PTC) score, CNIT, and other findings were also recorded [Table 1].
Table 1: Diagnostic criteria for reporting renal allograft biopsy and grading of histological findings.

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   Statistical Analysis Top

Statistical analysis was performed using IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, USA). Continuous data are presented as mean ± standard deviation. Student’s t tests were used to compare two groups and analysis of variance for more than two groups. Categorical data were compared using χ2 tests or Fisher’s exact tests. Kaplan–Meier curves and log-rank tests were used to describe and compare patient and death-censored graft survival rates. P <0.05 was considered statistically significant.

   Results Top


Sixty-one (4.1%) of 1520 biopsies revealed changes of TMA with significantly lower incidence in Group 1 compared to Group 2 observed by Chi-square test (P <0.001) [Table 2]. Seventeen (1.9%) out of 882 biopsies of Group 1 and 44 (6.9%) of 638 biopsies of Group 2 revealed TMA. Group 1 with 17 patients included 12 males and five females, with mean age 36.8 ± 12.1 years and mean HLA-match 2.59 ± 1.23 out of 6. Donors were parents in 10 patients, spouses in four, and siblings in three patients. The most common etiologies of ESRD were unknown in seven (41.2%), chronic tubulointerstitial nephritis (CTIN) in four (23.5%), and other causes in remaining patients. Group 2 with 44 patients included 38 males and six females, with mean age of 35.9 ± 10.2 years and mean HLA-match of 2.12 ± 1.61. Donors were parents in 17, cross/extended family members in nine, spouse in eight, sibling in one, and deceased in nine patients. The most common etiology for ESRD was unknown in 50%, followed by other causes ranging from Alport’s syndrome, reflux nephropathy, glomerular diseases such as focal segmental glomerulosclerosis (FSGS), and others, and two patients had HUS. There was no significant statistical difference in demographics between the two groups. Systemic TMA was not observed in any patient.
Table 2: Patient-donor demographics of Group 1 patients transplanted under tolerance induction protocol and Group 2 patients transplanted under standard Tacrolimus based triple immunosuppression protocol.

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Biopsy findings

The biopsy findings have been presented in [Table 3]a. Mean biopsy time after transplantation was 5.1 ± 4.4 years in Group 1 and 2.3 ± 3.9 years in Group 2. In Group 1, the major associated findings with TMA were ABMR in 58.8%, TCMR in 11.8%, tacrolimus toxicity in 76.5%, and other findings such as patchy cortical necrosis and acute BK polyoma virus nephropathy in 35.3% of biopsies. The major findings in Group 2 biopsies were ABMR in 61.4%, TCMR in 25%, tacrolimus toxicity in 50%, and other findings in 18.2% of biopsies. Recurrence was observed in two biopsies. Rejection scores were more severe in Group 2 [Table 3]b. The risk for ABMR and TCMR in Group 1 was less compared to Group 2 with hazard risk ratio (HR) of 0.49 [confidence interval (CI) 0.22, 1.06] (P = 0.07) for ABMR and HR = 0.17 (CI: 0.04, 0.83) (P = 0.03) for TCMR. The risk for CNIT was less for Group 1; HR = 0.73 (CI: 0.35, 1.51) (P = 0.39).
Table 3:

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Interesting histopathology findings are depicted in [Figure 1] (A to D) and [Figure 2] (A to D). Combined lesions were also observed [Table 4]. All the lesions were observed at any time after transplantation, ranging from 1 day to more than 6 years after RT. There was no significant statistical difference between the two groups except for biopsy time (P = 0.03).
Figure 1: A. Group-1, 41 years male, end stage renal disease (ESRD) of unknown etiology, Donor-Cross, (0/6 match), transplant 6 years back under immunosuppression minimization protocol (date: 30th Nov,‘09); biopsy date: 20 June ‘15; presented with sudden rise in SCr 6.11 mg/dL (baseline: 1.31 mg/dL), Doppler: resistivity index: 0.86, Urine albumin 500 mg/dL, rest unremarkable; Immunosuppression: Cyclosporine (CsA), 3 mg/kgBW/day, Prednisone, 10 mg/day, Mycofenolate 360 mg BD. Donor specific antibodies were absent. Final diagnosis was CsA induced acute on chronic TMA, Banff type 6.
Histopathology displaying in 1A, interstitial fibrosis and tubular atrophy, aneurysmally dilated glomerular capillary lumina filled with fibrin/platelet thrombi, in 1B: subintimal arterial hyalinosis, afferent arteriolar dilatation of glomerular capillary, thickened and wrinkled membranes, in 1C, marked mesangiolyios and onion peeling of small caliber artery (depicted by blue arrow) vascular luminal recanalization (depicted by blue arrow) in 1D.
Figure 2A. Group-2: 41 years F, ESRD of unknown etiology, donor-husband (0/6 match), transplant dt: 21/9/‘18; biopsy date: 2/10/' 18, for proteinuria and rise in SCr 3.3 mg/dL (baseline: 1.31 mg/dL), Doppler: RI:1, diastolic flow absent, urine albumin 75 mg/dL, Tac level: 10.3 ng/ml, I.S.: Tac, 0.05 mg/kgBW/day, Pred. 20 mg/day, Mycofenolate 360 mg QID. Diagnosis on biopsy was made as Active ABMR with acute TMA, Banff update 2017, type 2, Rejection activity score: ag2 at0 av0 ai1, PTC score 2, C4d score 3
Histopathology displaying moderate to marked tubular injury in 2A, glomerulitis, mesangiolysis, aneurysmal dilatation and focal congestion of capillary lumina with swollen endothelial cells in 2B and 2C and diffuse circumferential C4d deposits along peritubular capillaries in 2D.

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Patient and graft survival

Mean follow-up after transplant was 7.51 ± 3.91 years in Group 1 and 4.48 ± 4.12 years in Group 2. Mean follow-up after biopsy was 2.27 ± 1.49 years in Group 1 and 0.63 ± 0.91 years in Group 2. Group 1 has longest follow-up of 15-years posttransplant and Group 2 has longest follow-up of 24 years posttransplant. Patient survival in Group 1 was 100% from 1–7 years and 77.8% from 8–15 years posttransplant [Figure 3]a and [Figure 3]b). Survival after biopsy was 94.1% at 1 year and 86.9% thereafter till 6 years post-biopsy. Patient survival in Group 2 was 97.7% at one year, 95.2% at 2 years, 92.2% from 3–6 years, and 80.7% from 7 to 24 years posttransplant. Patient survival after biopsy was 92.1% at 1 year and 88.3% thereafter till 5 years postbiopsy. One patient in Group 2 has survived for 24-year posttransplant. He manifested TMA at 23-year posttransplant to which, he lost his graft. The risk for mortality in Group 1 was less versus Group 2 [HR = 0.54, (CI: 0.089, 3.297)] (P = 0.51).
Figure 3: (a) Kaplan–Meier plot of patient survival of 2 groups from transplant date, (b) Kaplan Meier plot of patient survival of 2 groups from biopsy date.

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Death censored graft survival in Group 1 at 1, 5, 10, and 15 years post-transplant was 82.4%, 62.6%, 32.4%, and 12.2% in Group 1 and 65.4%, 26.3%, 8.8%, and 4.4% in Group 2. Graft survival up to 22 years was 4.4% and zero thereafter in Group 2. Group 1 was doing statistically significantly better than Group 2 (P = 0.01) [Figure 4]a and [Figure 4]b. Postbiopsy death-censored graft survival in Group-1 was 52.9% at 1 year, 31.8% at 2 years, and 15.9% at 3 and 4 years posttransplant. Patient surviving at 5 years had lost his graft in Group 1. In Group 2, survival was 20.3% at 1 year, 16.2% at 2 years, 10.8% at 3 years, and 5.4% at 4 years after biopsy. The risk for graft loss in Group 1 was less as compared to Group 2; [HR = 0.43 (CI: 0.213, 0.851)] (P = 0.02).
Figure 4: (a) Kaplan–Meier plot of death censored graft survival of 2 groups from transplant date, (b) Kaplan Meier plot of death censored graft survival of 2 groups from biopsy date.

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Mean SCr at the time of biopsy was 3.6 ± 14 mg/dL in Group 1, and 4.18 ± 0.12 mg/dL in Group 2. Mean SCr (mg/dL) was 1.23 ± 0.35, 1.25 ± 0.25, 1.54 ± 0.4 and 1.84 at 1, 5, 10, and 15 years posttransplant in Group 1, and 1.83 ± 1.46, 1.64 ± 0.52, 1.05 ± 0.07, 1.22 ± 0.14 in Group 2 [Figure 5]. The single patient in Group 2 with functioning graft after 15 years had SCr of 1.13 mg/dL at 22 years, after which he developed TMA and lost his graft. Group 1 had significantly better graft function than Group 2 at 1, 2, and 4 years posttransplant (P <0.01).
Figure 5: Graft function in terms of serum creatinine after transplantation in 2 groups.

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   Discussion Top

TMA can occur either for the first time after RT or may recur and its incidence has been reported to be 5.6 cases/1000 RT/year with 50% mortality rate of years after diagnosis.[1] De novo TMA and has worse prognosis than recurrent TMA.[8] In a United States Renal Data System (USRDS)-based meta-analysis by Reynolds et al, the incidence of recurrent TMA was only 12 compared to 112 patients with de novo TMA, although the risk of recurrent TMA posttransplant was 36.5 times higher in ESRD patients with HUS as compared compared to other causes (29.2% vs. 0.8%)/ Langer et al reported the incidence of de novo TMA to be 1.5%, whereas Schwimmer et al and Zarifian et al reported 3%–14% incidence of de novo TMA after RT. In a study of RAB, Radha et al reported an incidence of 9.1% TMA in 131 biopsies. In a retrospective study of 1540 RABs performed by Goplani et al, TMA was observed in 17 (1.1%) biopsies; nine patients developed HUS/TMA within 3 months of transplantation, and eight, between 3 months, and 1 year post-transplant.[9],[10],[11],[12],[13]

Out of the 12 TMA cases observed by Radha et al, five showed associated changes of CNIT, three had ABMR, one had Sirolimus toxicity, and other biopsies showed other pathologies such as viral infection.[12] In the current study of RAB, incidence of TMA was 4.1% of 1580 biopsies. In this study, the most common associated findings were ABMR in 60.6% (n = 37), CNIT in 57.4% (n = 35), and other findings in 22.9% (n = 14) biopsies. Recurrent TMA was found in two (3.3%) cases. These observations included combined lesions of ABMR + CNIT also. The typical histological features of TMA are noted mainly in the glomeruli and vessels in the form of intra-capillary accumulation of RBCs or their fragments, platelet/fibrin thrombi, endothelial cell swelling, and detachment from basement membrane, arteriolar thrombosis, mesangio-lysis, and in the healing phase, there will be “onion peeling” appearance of vessel walls due to hypertrophy.[1] These features were observed by us as well as in other studies also.[8],[11],[12],[13],[14],[15] Circumferential PTC C4d deposition, endarteritis, and complete vascular tree affection are a feature of ABMR unlike CNI-induced TMA.[15] The current study also has similar observations. The occurrence of TMA due to cyclosporine (CsA) toxicity was first reported by Shulman et al in 1981.[14] In a prospective study of 257 RABs of patients transplanted under an Ahmedabad Tolerance Induction Protocol (ATIP) (n = 207) compared with controls transplanted under standard CsA based triple immunosuppression (n = 50) by Mohapatra et al, TMA manifested as CsA toxicity in 4% of ATIP group and none in controls in the first 3 months of transplantation, and in 2.4% of ATIP group and 5% of controls after 3 months of transplantation.[16] This study also reported that tissue toxicity was observed in spite of normal circulating CsA trough levels. Interestingly, control group had higher CsA trough levels of 240.5 ng/mL than ATIP group which displayed trough levels of 110.3 ng/mL. In study by Goplani et al, two out of 17 patients had recurrent HUS and 15 were drug induced (12 with CsA, 3 with Sirolimus).[12] Graft-limited TMA was seen in 58.8% in this study. Schwimmer et al observed that only 30% of TMA was localized to the renal allograft.[10] This appears different than observations in the past, as well as in the present study with all of patients showing graft-limited TMA.[12],[13],[16] Tacrolimus was introduced in 1989 to overcome the side effects of CsA; however, tacrolimus toxicity was also observed in grafts with the incidence of tacrolimus-associated TMA reports of 3%–14%.[17],[18] In the series of Radha et al, tacro- limus was responsible for 25% of TMA.[13] Our patients were mainly on tacrolimus-based immunosuppression. In study by Goplani et al, graft function recovered in 12 out of 17 patients, with 60% recovery in HUS group and 80% recovery in TMA group, establishing that TMA has better chances of recovery than HUS where systemic involvement is observed. Schwimmer et al observed that patients with localized TMA had 100% recovery whereas if there was systemic involvement, 58% were dialysis dependent and 38% lost their grafts.[10] Noris and Remuzzi reported 1-year graft survival of 32% for deceased donors and 50% for live donors.[15] Radha et al reported 50% graft survival at 1 year.[13] USRD data registry by Reynolds et al reported 50% patient survival at 3 years. Zarifian et al and Satoskar et al reported about 40% graft loss within years of transplantation when it was de novo TMA.[1119] The current study shows 88% patient survival and 8.1% graft survival at 4 years.

It was observed by Le Quintrec et al that there was underlying complement mutation abnormality in one-third of patients with de novo posttransplant TMA.[20] They observed that about 29% of patients had mutations in complement factor H/I or both, 25% patients had low complement factor B and/or low C3, suggesting that there was a role of alternate pathway complement activation in causation of posttransplant de novo TMA. The current study does not have complement factor assays or ADAMTS13 deficiency studies available. ABMR is well known to be associated with posttransplant TMA.[1] Endothelial cells are a well-known target of alloimmune response. PTC-C4d staining, which is a marker for ABMR, has been reported to be present in 16.2% of biopsied recipients with TMA.[1],[21] Satoskar et al reported an incidence of 55% of de novo TMA patients who express diffuse PTCC4d positivity.[19] In the current study, about 80% of biopsies with ABMR had diffuse or focal C4d positivity. Moreover, Satoskar et al and Wu et al observed that ABMR and TMA together were predictors of worse graft outcome.[19],[22] Viral infections such as BKV, CMV, hepatitis C, parvovirus, and antiviral medications such as ribavirin and interferon are known to be involved in posttransplant TMA.[23],[24],[25],[26],[27],[28],[29] In the current study, ABMR and CNIT were the most common associated findings, followed by FSGS/collapsing glome-rulopathy and acute BKV nephropathy. We have also observed high incidence of graft loss, especially when it was combined ABMR and CNIT with TMA. Plasmapheresis/IVIg, Eculizumab, Belatacept, and withdrawal of CNI have been attempted with variable success to treat TMA; however, none of the treatment protocols has proved to be curative.[30],[31],[32] In the current study, in Group 1 patients subjected to pretransplant SCT followed by immunosuppression minimization, there was lower incidence of ABMR associated TMA. In addition, CNI avoidance also could have prevented TMA since many of the patients with TMA associated with CNIT in this group recovered after discontinuation of tacrolimus. Our previous studies have established the safety of protocol using SCT where the incidence of rejections is minimized and CNI can be withdrawn.[7],[33],[34] This approach can help in minimizing TMA in posttransplant patients.

   Limitations of the Study Top

The current study has the central theme of histopathological observations. We could not carry out gene mutation studies on complement factors H/I/B. We have also not included the treatment aspects of these patients.

To conclude, irrespective of etiology, post-transplant TMA is a bad prognosticator for RT patients. SCT can help in minimizing the incidence of TMA since the rejection episodes are significantly reduced and weaning off CNI is fairly successful. Multicenter studies are required in this direction.

   Acknowledgments Top

We are grateful to 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.

   References Top

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George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014; 371:654-66.  Back to cited text no. 4
Loupy A, Haas M, Solez K, et al. The Banff 2015 Kidney Meeting Report: Current challenges in rejection classification and prospects for adopting molecular pathology. Am J Transplant 2017;17:28-41.  Back to cited text no. 5
Roufosse A, Simmonds N, Clahsen-van Groningen Met al. A 2018 reference guide to the banff classification of renal allograft pathology. Transplantation 2018;102:1795-814.  Back to cited text no. 6
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Abbas F, El Kossi M, Kim JJ, Sharma A, Halawa A. Thrombotic microangiopathy after renal transplantation: Current insights in de novo and recurrent disease. World J Transplant 2018;8: 122-41.  Back to cited text no. 8
Langer RM, Van Buren CT, Katz SM, Kahan BD. De novo hemolytic uremic syndrome after kidney transplantation in patients treated with cyclosporine-sirolimus combination. Transplantation 2002;73:756-60.  Back to cited text no. 9
Schwimmer J, Nadasdy TA, Spitalnik PF, Kaplan KL, Zand MS. De novo thrombotic microangiopathy in renal transplant recipients: A comparison of hemolytic uremic syndrome with localized renal thrombotic microangiopathy. Am J Kidney Dis 2003;41:471-9.  Back to cited text no. 10
Zarifian A, Meleg-Smith S, O’donovan R, Tesi RJ, Batuman V. Cyclosporine-associated thrombotic microangiopathy in renal allo-grafts. Kidney Int 1999;55:2457-66.  Back to cited text no. 11
Radha S, Tameem A, Sridhar G, et al. Thrombotic microangiopathy in renal allo-grafts. Indian J Nephrol 2014;24:24-7.  Back to cited text no. 12
[PUBMED]  [Full text]  
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Shulman H, Striker G, Deeg HJ, Kennedy M, Storb R, Thomas ED. Nephrotoxicity of cyclosporin A after allogeneic marrow transplantation: Glomerular thromboses and tubular injury. N Engl J Med 1981;305:1392-5.  Back to cited text no. 14
Noris M, Remuzzi G. Thrombotic micro-angiopathy after kidney transplantation. Am J Transplant 2010;10:1517-23.  Back to cited text no. 15
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Satoskar AA, Pelletier R, Adams P, et al. De novo thrombotic microangiopathy in renal allograft biopsies-role of antibody-mediated rejection. Am J Transplant 2010;10:1804-11.  Back to cited text no. 19
Le Quintrec M, Lionet A, Kamar N, et al. Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation. Am J Transplant 2008;8:1694-701.  Back to cited text no. 20
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Petrogiannis-Haliotis T, Sakoulas G, Kirby J, et al. BK-related polyomavirus vasculopathy in a renal-transplant recipient. N Engl J Med 2001;345:1250-5.  Back to cited text no. 25
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Waldman M, Kopp JB. Parvovirus-B19-associated complications in renal transplant recipients. Nat Clin Pract Nephrol 2007;3:540-50.  Back to cited text no. 27
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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
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DOI: 10.4103/1319-2442.308342

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


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