Nontraditional cardiovascular risk factors and structural atherosclerosis in stable renal transplant recipients

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indian journal of transplantation 9 (2015) 47–60

offered rATG induction based on their socioeconomic status, risk of immunological injury and infections. Patients who were at a higher risk for DGF or AR received high dose rATG (≥4.5 mg/ kg) and all other patients received either low dose ATG (<4.5 mg/kg;or usually 3 mg/kg) or no induction. All patients received triple immunosuppressant consisting of Tacrolimus, MMF and Steroids. CDC cross match was negative in all patients. Primary endpoint was development of acute rejection within 6 months post transplant and secondary were acute rejections at 1 year, graft survival at 1 year and at end, patient survival at 1 year and at end of study, S. Creat at 7 days, 6 months and 1 year. Results: Of 110 recipients, 98 (89%) were men. The mean age of recipients was 37  10.4 yrs range (18–62 yrs). Mean follow up period was 1.46 yrs (range 1–3 yrs). 58 patients had no induction, 47 patients received low dose ATG and 5 patients received high dose ATG. 9 patients were lost to follow-up. 23 (24%) rejections occurred in the 96 patients analysed. 16 (65%) AMR, 5 (22%) ACR and 2 (8.6%) were mixed. Incidence of BPAR was more in no induction 17 (31%) compared to low dose ATG recipients 6 (14.3%) (p = 0.05). High incidence of rejections within 1month was seen 19 (82.6%) and they were more in no induction recipients 16 (29.6%) vs 3 (7%) (p = 0.006). 3 rejection occurred within 1–6 months and 1 after 6 months. Out of 16 early rejections in no induction recipient, 5 (31%) patients had complete, 7 (44%) had partial recovery and 4 (25%) grafts were lost. In induction recipient of 6 rejections 2 (40%) had complete, 4 (60%) had partial recovery and no graft lost. Total 6 deaths and 5 grafts were lost. Graft survival, death censored graft survival & patient survival at1year is 88%, 91% & 93%. Conclusions: Overall rejection rate is 24%in living donor kidney transplant recipients. AMR remains an important cause of acute rejection and graft loss in the early post-transplant period. AR are less frequent after 6 months. No induction recipients had more severe degree of early rejections and early graft loss. http://dx.doi.org/10.1016/j.ijt.2015.09.024 Abstract #: ISOT2015-26 Rituximab induction in renal transplantation Prashant Rajput, Bharat Shah, Zaheer Virani, Hepal Vora, Jasleen Kaur, Vijay Dawane, Shrikant Adate Institute of Renal Sciences, Global Hospital, Mumbai, India Background: Rituximab is a chimeric anti CD 20 monoclonal antibody that leads to B cell depletion and has long-term effects on plasma cells and B cell modulation of T cell responses. Its successful use in ABO-incompatible renal transplant recipients has resulted in comparable or even better 10 year survival compared to ABO compatible renal transplants. This prompted us to use Rituximab as an induction agent in all renal transplants. Aims: To evaluate the effectiveness of Rituximab as an induction agent in renal transplant recipients. Methodology: One hundred and thirty three patients who underwent renal transplant between January 2012 and January 2015 were part of this retrospective analysis. Patients were divided into two groups: Rituximab-induction group (n = 74) receiving induction regimen containing Rituximab (200–400 mg) plus Anti-Thymocyte Globulin (ATG) (1–5 mg/ kg) and non-Rituximab induction (n = 59) receiving induction regimen containing ATG. Maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate sodium and corticosteroids. Data was analyzed using descriptive statistics; mean and standard deviation (SD) for continuous

variables and frequency and percentages for categorical variables. Chi-square test was used to find the association between Rituximab induction and no induction group (a p value of <0.05 was considered statistically significant). Results: There was no significant difference in age, sex, etiology of CKD and HLA Mismatches in the two groups. The Rituximab induction group was associated with significantly lower incidence of ACR, AMR, CAN and NODAT compared to the non induction group (p ≤ 0.01). The incidence of infections was statistically nonsignificant in both the groups. Rituximab Induction was associated with higher late onset neutropenia (p ≤ 0.046). Incidence of graft loss was comparable between two groups (3 vs. 4 in rituximab-induced and non-rituximab induced groups respectively; p = 0.4861). Mortality rate was higher in the Rituximab induction group compared to the no induction group (7 vs. 2; p = 0.0451). Six out of seven deaths in the Rituximab induction group were due to infections (fungal infections – 66.6%). The graft survival (Death censored) and patient survival at 3 years in patients treated with Rituximab was 95.5% and 90.5% and patients with no Rituximab was 93.2% and 98.3%. Conclusions: Rituximab, as an induction agent, was associated with a lower incidence of ACR, AMR, CAN and NODAT compared to non-rituximab induced regimen. However Rituximab induction was associated with higher incidence of neutropenia resulting in severe fatal infections in some patients. http://dx.doi.org/10.1016/j.ijt.2015.09.025 Abstract #: ISOT2015-51 Nontraditional cardiovascular risk factors and structural atherosclerosis in stable renal transplant recipients Sandeep Mahajan, Bakshish Singh, Atin Kumar, Anoop Saraya, R. Lakshmi All India Institute of Medical Sciences, New Delhi, India Background: Cardiovascular diseases (CVDs) are major cause of mortality in CKD patients both before and after transplantation. Non-traditional CVD risk factors (NTRFs) implicated for this in CKD patients are not well-studied posttransplant. Aims: Look at carotid intimal media thickness (CIMT) and CVD risk factors in stable renal transplant recipients (RTR). Methodology: Demographic and clinical data, duration of transplant, biochemical and lipid profile, eGFR (MDRD, 4 variable), Hs-CRP and homocysteine (Hcy) of 69 stable renal transplant recipients (55 males) and 40 age and sex matched controls were noted. Patients having DM, vascular disease and serum creatinine ≥2 mg/dl were excluded. Oxidative stress (OS) markers, thiobarbiturate acid reactive substances (TBARS) and total antioxidant capacity (TAC); CIMT and endothelial function (EF) assessed by flow mediated dilatation of brachial artery (endothelium dependent, EDD) and endothelium independent dilatation (EID) were also determined. Results: Mean age, duration post-transplant and eGFR were 33.2  9.2 years, 32.1  42.4 months and 71.7  14.3 ml/min respectively. Compared to controls transplant patients had higher systolic and diastolic blood pressures (126.1  8.7 and 81.8  4.5 vs 119  2.9 and 78.4  2.7 mmHg), LDL/HDL cholesterol ratio (2.72  0.77 vs 1.84  0.34), homocysteine (20.3  8.9 vs 6.1  0.1 mmol/L) and Hs-CRP (2.27  3.33 vs 0.86  0.89 mmol/L) (p < 0.001 for all). They had poorer EDD (7.78  2.60 vs 12.48  2.14%), higher TBARS (5.41  5.63 vs 1.52  1.01 nmol/ml) and CIMT (0.78  0.12 vs 0.29  0.02 mm) (p < 0.001 for all). However, EID and TAC were similar. On

indian journal of transplantation 9 (2015) 47–60

multivariate analysis of all parameters, CIMT correlated only with age (b = 0.238, p = 0.03) and eGFR (b = 0.248, p = 0.01). Conclusions: Higher burden of NTRFs and increased CIMT was noted in stable post-transplant patients. Factors influencing this high atherosclerotic profile need to be delineated. http://dx.doi.org/10.1016/j.ijt.2015.09.026 Abstract #: ISOT2015-71 An increased P-glycoprotein positive Th17 cell is associated with late renal allograft dysfunction Brijesh Yadav, Narayan Prasad, Vikas Agarwal Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India Background: Th17 is a proinflamatory subsets remained refractory under calcineurin inhibitor based immunosuppressive regimen. Although etiology is unknown. Recent studies have suggested, Th17 have pleotropic function, induce plasma cell antibody secretion, neutrophil recruitment, IL-17A induces pulmonary, lung fibrosis. Permeable glycoprotein (Pgp) is a trans-membrane glycoprotein efflux xenobiotics, cytokines, and immunosuppressive regimen from the cytoplasm and limits their bioavailability to cell. Aims: To determine the circulating frequency of Th17, Pgp + Th17, soluble IL-17A level and their correlation with renal graft functions parameters (24 hrs Proteinuria, Serum creatinine level, eGFR). Methodology: Twenty five patients with stable graft function (SGF) (> 10% rise in serum creatinine level from baseline which was stable in last six month, No evidence of active proteinuria). Twenty five patients were of active late renal allograft dysfunction (LAD), showing serum creatinine >1.5 mg/dl, nephrotic range proteinuria, were recruited in study. Blood sample was withdrawn for flow cytometry frequency determination and IL-17 level by ELISA assay. The mean values in different groups were compared with Man Whitney U test for continuous variables and Chi square test for categorical variables. Pearson correlation was applied for correlation analysis. Results: The %frequency of circulating CD4+Th cell was significantly high in LAD (34.97  5.10%) compare to SGF (31.71  3.49; P = 0.011). Th17 (CD4+IL 17A+) cell in LAD was (7.16  1.96) compare to SGF (4.12  1.57; P < 0.001). The serum IL17A level (pg/ml) in LAD was (87.56  18.77) compare to SGF (32.54  8.65; P < 0.001). The ratio of Th17/CD4+Th cell in LAD was (0.210  0.069), compare to that of SGF (0.130  0.051; P < 0.001). Similarly, the frequency of Pgp+CD4+Th cell in LAD was (17.02  6.96) compare to SGF (12.28  4.14; P = 0.005). Frequency of Pgp+Th17 (Pgp+IL-17A+ CD4+ triple positive) cell in LAD was (2.49  1.06) compare to SGF (0.982  0.66; P < 0.001), Serum creatinine was positively correlating with Th17 (r = 0.529, P < 0.001), Pgp+Th17 (r = 0.392, P = 0.005), 24 hrs proteinuria with Th17 (r = 0.614, P < 0.001) cell, Pgp +Th17 (r = 0.656, P < 0.001).(eGFR) was negatively correlating with Th17 cell (r = 0.545, P < 0.001), Pgp+Th17 cell (r = 0.382, P = 0.006). Conclusions: Higher Pgp expression on Th17 cell surface may be the cause of Th17 cell dysregulation and chronic allograft dysfunction. An inhibition of Pgp together with immunosuppressive medicine may be used to treat Th17 mediated allograft dysfunction. http://dx.doi.org/10.1016/j.ijt.2015.09.027 Abstract #: ISOT2015-40 Antibody mediated rejection of renal transplantation – Clinicopathological correlation

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Bavikar Suhas, Oswal Ajay, Swarnalata Gowrishankar Kamalnayan Bajaj Hospital, Aurangabad, Apollo Hospital, Hyderabad, India Background: kidney transplant rejection is classified as cellular, humoral or mixed. Definitive diagnosis of antibodymediated rejection was made if some of the 3 observations were noted but not all were present: (1) Morphological evidence of tissue injury. (2) PTC C4d positivity – immunopathologic evidence for antibody action. (3) Serologic evidence for circulating donor specific antibody. Antibody mediated rejections with DSA positivity behaved differently to treatment. Aims: Treatment responders and nonresponders were analysed for clinical presentations, DSA titres, intervention, and histopathologicaly in ABMR in retrospective fashion in 138 cases over 3 year 2010–2013. Methodology: Antibody mediated (C4d positive and DSA by luminex positive, C4d positive – DSA negative, DSA+ and c4d –ve?) rejection vs T cell mediated rejection in 81 graft biopsies done over 3 year in 138 kidney transplant recipients – were compared for treatment outcomes in retrospective fashion indications for biopsy after kidney transplant were (1) persistent Proteinuria, Decrease in GFR on (nuclear scan); (2) rise in Creatinine after reaching Nadir, (3) oliguria after transplant, biopsy diagnosis were classified into C4d positive vs negative rejections. Effective treatment given was methylprednisolone 500 mg daily for 3 days started on suspicion of rejection, sending for graft biopsy with c4d staining in all before first dose of pulse steroids. C4d staining positive cases with positive DSA in 3 first 30 post-operative day period cases recd. rabbit thymoglobulin 3 mg/kg over 3 days and 5 mg/kg over 5 days in one case. All these patients recovered. Results: Outcome in early ABMR was good with steroids, RATG, TPE. Favourable histology feature was leukocytes in PTC and changes of ATN as against interstitial n vascular inflammation in late ABMR, and TGP, IFTA in chronic ABMR. DSA involved in early group were/PREEXISTING (NOT done before KT). In late and chronic ABMR-DSA were de novo observed in 50% cases before rejection. Grafts could not be salvaged in late acute ABMR, even with TPE, Steroid and RATG pulse. In chronic ABMR treatment did not make any difference with higher titres >10,000 MFI values. Titres with <6000 MFI cases benefited after TPE, steroid pulse and bortezomib as their albuminria and creeping creatinine stabilised. Conclusions: Lack of correlation between DSA,C4d. graft biopsy and response to treatment Response to treatment is a matter of timely intervention If all patients were tested for pretransplant LCM by CDC, flow and DSA by Luminex cross match, Early ABMR could have been predicted, prevented. http://dx.doi.org/10.1016/j.ijt.2015.09.028 Abstract #: ISOT2015-39 Can the DJ stent be dispensed? A prospective randomised study in renal transplant recipients L.N. Murthy, Charan Srinivas, Rahul Devraj, Vidyasagar Ramachandraih, Ramreddy Department of Urology & Renal Transplantation, Nizam's Institute of Medical Sciences Hyderabad, India Background: The use of prophylactic double-J ureteric stent during renal transplantation is debatable. There were studies in literature in favor and against to routine stenting during ureteroneocystostomy. The authors who favor stenting claim that the incidence of urological complications were reduced and thereby decreasing the post op morbidity. On the Contrary, some studies showed routine stenting is unnecessary as