[Show abstract][Hide abstract] ABSTRACT: The role of neopterin as a marker of cell-mediated immunity for immunological monitoring after transplantation is of great potential interest. Neopterin levels among hepatitis C virus (HCV)-positive recipients of living-donor renal transplantation (LDRT) have not been previously described.
Twenty-two HCV-positive (group I) and 10 HCV-negative (group II) recipients of LDRT were serially monitored for serum neopterin levels by enzyme-linked immunosorbent assay (ELISA). Group I patients were monitored thrice, ie, before transplantation, day 10, and 6 months post transplantation, while group II patients were monitored twice (day 10 and 6 months post transplantation). Peripheral blood T-lymphocyte subsets (CD3, CD4, CD8, CD4(+)CD25(+), CD16+56) and Th1/Th2 cytokines were monitored concomitantly by flow cytometry.
Ten days post transplantation, there was a significant increase in neopterin and neopterin/creatnine levels among group I patients. There was a positive correlation between activated T-lymphocyte (CD4(+)CD25(+)) and neopterin early post transplantation (day 10). Th2 cytokines IL-10 and IL-5 showed a positive correlation with neopterin levels on day 10 and 6 months post transplantation, respectively. Neopterin levels did not show association with either HCV viral load or allograft rejection among our study cohort.
Increased monocyte/macrophage activation with elevated serum neopterin was detected among group I patients on day 10 post transplantation, but it could not predict rejection. It appears that IL-10 either from a regulatory or nonregulatory source helps in the maintenance of stable graft early post transplantation. Further, it would be of interest to assess the role of neopterin in chronic allograft nephropathy and long-term graft outcome.
[Show abstract][Hide abstract] ABSTRACT: AimThis pilot study assesses the safety and feasibility of autologous mesenchymal stromal cell (MSC) transplantation in four patients undergoing living donor renal transplantation, and the effect on the immunophenotype and functionality of peripheral T lymphocytes following transplantation.Methods
All patients received low dose ATG induction followed by calcineurin inhibitor-based triple drug maintenance immunosuppression. Autologous MSCs were administered intravenously pre transplant and day 30 post-transplant. Patients were followed up for 6 months. The frequency of regulatory T cells and T cell proliferation was assessed at different time points.ResultsNone of the 4 patients developed any immediate or delayed adverse effects following MSC infusion. All had excellent graft function, and none developed graft dysfunction. Protocol biopsies at 1 and 3 months did not reveal any abnormality. Compared to baseline, there was an increase in the CD4+CD25+FOXP3+ regulatory T cells and reduction in CD4 T cell proliferation.Conclusion
We conclude that autologous MSCs can be used safely in patients undergoing living donor renal transplantation, lead to expansion of regulatory T cells and decrease in T cell proliferation. Larger randomized trials studies are needed to confirm these findings and evaluate whether this will have any impact on immunosuppressive therapy.
[Show abstract][Hide abstract] ABSTRACT: Estimation of the prevalence of high-risk human papillomavirus (HPV) genotypes in female renal transplant recipients is important for formulating strategies for prevention and screening of cervical cancer in the susceptible group. Data from developing countries are very limited. The study was prospective, cross-sectional, and hospital-based. Female renal transplant recipients, who had received the graft at least 6 mo earlier, were enrolled. Women who visited the outpatient unit for varied complaints and who underwent a normal cervical examination were recruited as controls. A pap smear was obtained in all women. HPV genotyping array kit was utilized for identifying 21 HPV genotypes. Forty renal transplant recipient women and 80 controls were enrolled. The median age of cases and controls was 40 yr (range, 24-69 yr) and 38 yr (range, 23-72 yr), respectively. The mean duration since transplant was 53±42.6 mo (range, 6-168 mo). There was no evidence of cervical dysplasia in any pap smear. High-risk HPV was detected in 32.5% (13/40) and 17.5% (14/80) of cases and controls, respectively (P=0.18). Of the 21 genotypes screened, 7 subtypes were detected. HPV 16 and 31 were the most common (5/13; 38.5%) subtypes observed in the cases, followed by HPV 18 (30.7%). HPV 16 was the most common subtype in controls (10/14; 71.4%). Five (38.5%) renal transplant recipients harbored multiple HPV genotypes, as compared with 4 (28.6%) controls (P=1.0). The prevalence of high-risk HPV in female renal transplant recipients was 1.9 times that observed among controls, although there was no evidence of cervical dysplasia.
International Journal of Gynecological Pathology 07/2014; 33(5). DOI:10.1097/PGP.0b013e3182a54ada · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Deceased donor organ program is still in infancy in India. Assessing deceased donation potential and identifying barriers to its utilization are required to meet needs of patients with organ failure. Over a 6-month period, we identified and followed all presumed brainstem dead patients secondary to brain damage. All patients requiring mechanical ventilation with no signs of respiratory activity and dilated, fixed and non-reacting pupils were presumed to be brainstem dead. All events from suspicion of brainstem death (BSD) to declaration of BSD, approach for organ donation, recovery and transplants were recorded. Subjects were classified as possible, potential and effective donors, and barriers to donation were identified at each step. We identified 80 presumed brainstem dead patients over the study period. The mean age of this population was 35.9 years and 67.5% were males. When formally asked for consent for organ donation (n=49), 41 patients’ relatives refused. The conversion rate was only 8.2%. The number of possible, potential and effective donors per million population per year were 127, 115.7 and 9.5, respectively. The poor conversion rate of 8.2% suggests a huge potential for improvement. Family refusal in majority of cases reflects poor knowledge and thus, warrants interventions at community level.This article is protected by copyright. All rights reserved.
Transplant International 05/2014; 27(10). DOI:10.1111/tri.12355 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: IgA nephropathy, the most common primary glomerulonephritis worldwide, can lead to end-stage renal disease and kidney transplantation. Disease recurrence frequently occurs after transplantation. We investigated the predictive value of three markers including galactose-deficient (Gd) IgA1, IgG anti-IgA autoantibodies, IgA-soluble (s) CD89 complexes for IgA nephropathy recurrence. The efficacy of intravenous pulse steroid administration for treatment of recurrent IgA nephropathy was evaluated.Methods: The IgA nephropathy recurrent group (R group, n=11) was compared to matched patients transplanted for IgA nephropathy but without recurrence (NR group, n=13) and healthy subjects (n=22) for proportions of serum Gd-IgA1, IgA-IgG complexes and IgA-sCD89 complexes. Efficacy of pulse steroid therapy in reducing proteinuria was analysed in kidney transplant recipients R group.Results: Pre-transplantation serum proportion of Gd-IgA1 and IgA-IgG complexes were higher in R group compared to NR g
[Show abstract][Hide abstract] ABSTRACT: Glomerular diseases of the transplanted kidney are the most important cause of poor long term outcome. The estimation of the magnitude of this problem and an elucidation of pathogenic mechanism is essential for improvement of graft survival. This study from the Indian subcontinent aims 1) to determine the incidence of Transplant Glomerulopathy (TG) and Thrombotic Microangiopathy (TMA) in a large cohort of indicated renal transplant biopsies, 2) to evaluate the histological and ultrastructural features of TG and TMA and 3) to assess the relationship between the two glomerular lesions. Out of a total of 1792 indication renal transplant biopsies received over 5 years (2006 to 2010), 266 biopsies (of 249 patients) had significant glomerular pathology and were further analyzed along with immunofluorescence, electron microscopy (EM) and C4d immunohistochemistry. TG is the most common glomerular lesion followed by TMA seen in 5.97% and 5.08% of allograft biopsies respectively which constitutes 40.23% and 34.2% of biopsies with significant glomerular lesions. Pathologic antibody mediated rejection (AMR) is associated with both TG and TMA in 71% and 46.5% respectively. A coexistent TG was found in 18.4% of biopsies with TMA. Endothelial swelling with sub-endothelial widening, a feature of TMA, is also seen in early TG by EM. Our findings support the concept that TG evolves from a smouldering TMA of various causes. This article is protected by copyright. All rights reserved.
Transplant International 03/2014; 27(8). DOI:10.1111/tri.12331 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was designed to compare the outcomes of spousal donor (SD) with related donor (RD) kidney transplants performed at our center between January 2010 and October 2012. A total of 323 adult, ABO-compatible kidney transplants (SD 150 [46.4%], RD 173 [53.6%]) were included. Data on outcomes at 6 months post-transplant was collected retrospectively (2010-2011) and prospectively (January-October 2012). Majority of the donors (SD 88%, RD 72.2%) were females. In the SD group, donors were younger (SD 35.6 ± 8.2 years, RD 45.2 ± 11.5 years; P < 0.0001), whereas recipients were older (SD 42.2 ± 8.3 years, RD 30.0 ± 9.5 years; P < 0.0001). A significantly higher proportion of patients in the SD group were given induction therapy (43% vs 12%; P < 0.001). Biopsy proven acute rejections were more common in the RD group (16% vs 28.3%; P = 0.01). Majority (80.8%) of the acute rejections occurred in the first 2 weeks post-transplant in both groups. Isolated acute cellular rejections (ACRs) and isolated antibody mediated rejections constituted 50% and 25% of rejection episodes in both groups, whereas the remainder had histological evidence of both. The proportion of steroid responsive ACRs was similar in both groups (SD 83.3%, RD 65.4%; P = 0.2). The number of patients with abnormal graft function at the end of the study was higher in the RD group (2.3% vs. 12.3%; P = 0.001). Patient survival and infection rates were similar in the two groups. We conclude that short-term outcomes of SD transplants are not inferior to RD transplants. Lesser use of induction therapy in the RD group may explain the poorer outcomes as compared to the SD group.
Indian Journal of Nephrology 03/2014; 24(1):3-8. DOI:10.4103/0971-4065.125046
[Show abstract][Hide abstract] ABSTRACT: Background:
The attitude of healthcare workers towards organ donation can either facilitate or hinder the process of organ donation. We assessed the attitude of healthcare workers employed in intensive or emergency care units of our hospital towards organ donation, and the influence of various factors on willingness for self-organ donation after death.
All doctors, paramedical workers, nursing staff and other staff members working in six distinct intensive or emergency care units in the hospital were requested to fill a completely anonymous, voluntary and self-administered questionnaire. Younger individuals, women and nurses constituted a majority of the study population.
The questionnaire completion rate was 99%. About 55% of the study population were agreeable to donating organs after death and 27% were undecided. The factors that positively influenced their willingness to donate organs after death were favourable attitude of the spouse, religious beliefs supporting organ donation, knowledge of hospital's organ transplant programme, personal experience of the organ donation scenario, having ever donated blood or involvement in social activities, willingness to become an eye donor and willingness to become a living kidney donor.
A largely favourable attitude towards organ donation was seen in our study population. However, the study reflects incomplete knowledge leading to confusion and thus, desire to know more among participants with respect to various aspects regarding organ donation. The factors identify that positively influence decisions regarding organ donation can be used as direct interventions.
The National medical journal of India 11/2013; 26(6):322-6. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-depleting antibody induction has the best safety profile in transplant recipients without an increased risk of infection or malignancy. This observational study was performed in intermediate immunologic risk live donor renal transplants to assess basiliximab efficacy in patients on tacrolimus, mycophenolate, and prednisolone immunosuppression. A total of 46 patients on basiliximab induction were compared to risk matched 56 controls at the end of 6 and 12 months post-transplant. An additional cost of approximately Rs. 100,000/patient was incurred by the basiliximab group. The incidence of biopsy proven acute rejection in the control group (12.5%, 6 months and 20.5%, 1 year) and the basiliximab group (13%, 6 months and 18.9%, 1 year) was similar. At 6 months, there was a non-significant trend toward more steroid sensitive rejections and better glomerular filtration rate preservation in the basiliximab group (83.3%, 71.9 ml/min) versus the control group (28.6%, 62.2 ml/min). However, this difference was lost at 1 year (70.1 ml/min vs. 67.6 ml/min). The incidence of infections was similar and none of the patients had a malignancy. Death censored graft survival (94.6% basiliximab and 94.8% control) and the mean number of hospitalizations for all reasons at the end of 1 year were not different among the two groups. In our study, basiliximab induction did not confer an additional advantage in the intermediate risk live donor transplants in patients on tacrolimus and mycophenolate based triple drug immunosuppression.
Indian Journal of Nephrology 11/2013; 23(6):409-12. DOI:10.4103/0971-4065.120332
[Show abstract][Hide abstract] ABSTRACT: Measures to prevent chronic calcineurin inhibitor (CNI) toxicity have included limiting exposure by switching to sirolimus (SIR). SIR may favorably influence T regulator cell (Treg) population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR) and Treg frequency.
In this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR) at 180 days. Treg population was estimated by flowcytometry.
Baseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94±11.78 vs 80.59±16.51 mL/min, p = 0.038). Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in Treg population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event.
A deferred pre-emptive switch over from CNI to SIR safely improves renal function and Treg population at 6 months in living donor kidney transplant recipients. Registered in Clinical Trials Registry of India (CTRI/2011/091/000034).
PLoS ONE 10/2013; 8(10):e75591. DOI:10.1371/journal.pone.0075591 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication of organ transplantation. This study was a retrospective analysis of 2000 patients who underwent renal transplantation over a period of 30 years (1980-2010). Forty malignancies were diagnosed in 36 patients. Of these, 29 patients (1.45%) had PTLD (7 females, 22 males) accounting for 72.5% of all malignancies after transplantation. Twenty-two (75.8%) developed non-Hodgkin lymphoma and seven patients (24.2%) had myeloma. Diagnosis was made by biopsy of the involved organ in 21 patients (72.4%) and aspiration cytology in five patients (17.2%). In three patients, the diagnosis was made only at autopsy. Mean age at the time of diagnosis of PTLD was 41.9 years (range 21-69 years). Time interval from transplantation to the diagnosis of PTLD ranged from 3 months to 144 months with a median of 48 months. Only five patients (17.2%) developed PTLD within a year of transplantation. Twelve patients developed PTLD 1-5 years and 12 patients 5-10 years after transplantation. Organ involvement was extra nodal in 18 patients (82%). Thirteen (59%) patients had disseminated disease and nine (41%) had localized involvement of a single organ (brain-3, liver-1, allograft-1, perigraft node-1, retroperitoneal lymph nodes-3). Infiltration of the graft was noted in two patients. Patients with myeloma presented with backache, pathological fracture, unexplained anemia or graft dysfunction. PTLD was of B cell origin in 20 cases (70%). CD 20 staining was performed in 10 recent cases, of which 8 stained positive. Of the 26 patients diagnosed during life, 20 (69%) died within 1 year of diagnosis despite therapy. In conclusion, PTLD is encountered late after renal transplantation in the majority of our patients and is associated with a dismal outcome. The late onset in the majority of patients suggests that it is unlikely to be Epstein Barr virus related.
Indian Journal of Nephrology 07/2013; 23(4):287-91. DOI:10.4103/0971-4065.114504
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: Renal allograft recipients with thrombophilia are at higher risk for early allograft loss, microvascular occlusion and acute
rejection with major consequences for allograft survival. The aim of the present study was to evaluate the prevalence of prothrombotic
risk factors in patients awaiting renal transplantation and its contribution to patient and transplant outcomes.
Methods: All patients with a history of a thromboembolic event, early or recurrent vascular access thrombosis, family history of thrombosis,
or multiple miscarriages underwent laboratory screening for thrombophilia.
Results: Since the introduction of the screening for hypercoagulable risk factors, 156 candidates for renal transplantation underwent
laboratory evaluation. Eighty-eight patients (56%) exhibited at least one prothrombotic laboratory parameter, besides of isolated
hyperhomocysteinemia, which confirmed a thrombophilic state. Lupus anticoagulant, anticardiolipin and beta-2-glycoprotein
was present in 30%, 18% and 13%, and antithrombin III, protein C and protein S deficiencies in 11%, 8% and 10%, respectively.
Factor V Leiden mutation was present in only one patient and prothrombin gene G20210 mutation was not found. Among the 156
patients, 30 underwent renal transplantation and were followed for a median of 199 days (range, 9 – 418). All patients were
on triple immunosuppressive regimen compromising mycophenolate, tacrolimus and prednisone. Thrombophilia was identified in
16 (53%). Seventeen (57%) received perioperative anticoagulation with unfractionated heparin (9 patients with thrombophilia
and 8 without laboratory confirmed thrombophilia). Five (30%) of these patients developed perinephric hematomas. Three patients
with thrombophilia developed thrombotic complications (2 upper limbs deep-vein thrombosis and 1 allograft artery thrombosis)
and 1 patient without thrombophilia developed allograft vein thrombosis, p=0.35. Nine patients developed acute rejection (5 in the group with thrombophilia and 4 in the group without thrombophilia,
p=0.87). Mean glomerular filtration rate was similar between thrombophilic and non-thrombophilic patients in the last follow-up
(54±27 vs. 47±22 mL/min/1.73m², p=0.35). One graft loss and 1 patient death were observed in each group.
Conclusions: Prothrombotic risk factors, especially antiphospholipid antibodies, are highly prevalent in patients awaiting renal transplantation
with a clinical or familial history suggestive of thrombophilia, including early and recurrent vascular access failure. Despite
pre-transplant screening and perioperative treatment and/or monitoring, thrombotic and bleeding complications are still frequent