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The study of incidence based graft biopsies performed in live renal allograft recipients
indian journal of transplantation 9 (2015) 47–60
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ijt
Abstract Oro-Poster Abstract #: ISOT2015-59 One year survival analysis and factors predicting graft outcome in renal transplant recipients: A single centre experience G. Ragi Krishnan, Jacob George, Noble Gracious, M.K. Mohandas, Sajeev Kumar Department of Nephrology, Government Medical College, Trivandrum, India Background: Renal transplantation is regarded as the best treatment for patients with CKD. It improves the quality of life, reduces mortality, and offers a higher life expectancy when compared to dialysis. Most of the centres around the world report a short-term graft survival of 90–95%. There is paucity of data on graft and patient survival in renal transplant recipients from India. We present the one year survival analysis of renal transplants performed at our institution during last four and half years. Aims: (1) To analyze patient and graft survival in renal transplant recipients. (2) To analyze the association of factors predicting survival. Methodology: This is a observational, retrospective cohort study, including all the patients who underwent kidney transplantation in Government Medical College, Trivandrum from February 2nd, 2010 to July 31, 2015. All patients received triple drug immunosuppression. Patients in high risk group received induction therapy with IL-2 receptor blockers/ antithymocyte globulin. Demographic, clinical, laboratory, pretransplantation, and evolutionary clinical data after renal transplantation were obtained from patient records. Comparisons between the demographic and clinical characteristics of the patients who died and those of the patients who survived were conducted using the chi-squared (x2) test of association or, when indicated, Fisher's exact test. The Kaplan–Meier method was used for construction of survival curves. The Cox proportional hazards model was used for identification of factors associated to mortality and graft survival. Statistical analyses were conducted using SPSS software version 16. Results: A total of 126 transplants were done during the study period. Of this, 94 (74%) were males and 32 (26%) were females. 1 year patient survival was 91.8% and 1 year overall graft survival was 86%. Death censored graft survival was 94.1%. Functional graft survival was 91.7%. Death with functioning graft was the commonest cause of graft loss (33%). There were 4 cases of primary nonfunction, 3 cases of acute rejection and 3 were related to surgical complications. DGF was seen in 18 (14.2%) patients. There were 17 (13.5%) biopsy proven acute rejection (BPAR) episodes. Of these, 13 (77%) were antibody
mediated rejection and 6 (23%) were due to acute cellular rejection. 8.2% patients were lost, mainly due to infections. Primary graft nonfunction was noted in 2 patients (16%). Among risk factors for graft survival, rejection episodes, surgical complications and duration of HD prior to transplant were found to be significant. Conclusions: Our one year death censored graft survival rates (94%) are comparable with those reported from other international centres. Most common cause of graft loss was death with functioning graft followed by rejection and surgery related complications. http://dx.doi.org/10.1016/j.ijt.2015.09.002 Abstract #: ISOT2015-38 The study of incidence based graft biopsies performed in live renal allograft recipients Mukesh Goyal, U.N. Hegde, Sishir Gang, M.M. Rajapurkar, Kalpesh Gohel, Amit Jojera Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India Background: Several methods have been used to diagnose renal allograft dysfunction, including clinical evaluation and laboratory tests; however, core biopsy remains the ‘‘gold standard’’ for the diagnosis of renal transplant abnormality. Aims: To study the clinico-histopathological findings in the incidence based graft biopsies performed in live renal allograft recipients transplanted between 1st April 2013 and 31st December 2014. Methodology: Clinico-histopathological analysis with C4d immunostaining were performed on 167 needle core biopsies from 111 patients from live renal allograft recipients transplanted between and underwent incidence based graft biopsy between April 1, 2013 and December 31, 2014 at our center. Results: Major histological findings were normal pathology 34%, acute rejections 26%, CNI toxicity 11.3%, ATI 8.9%, pyelonephritis 3%, IFTA 4.7% and recurrence/glomerular disease was 1.7%. There was no major difference between various pathological groups as far as recipient and donor age, gender distribution, cold ischemia time, HLA mismatch, induction status, nonblood related donors and BMI was concerned. At 3 month post biopsy 60–80% incidences have shown recovery (complete or partial) across all histopathological groups except with histological features of mixed rejection (antibody mediated and cellular rejection) which shown recovery on only 33% incidences with highest incidence of graft function worsening (47%), graft and or patient loss (36%) and highest need for repeat biopsy (47%).
48
indian journal of transplantation 9 (2015) 47–60
Conclusions: Graft biopsy remains ‘‘gold standard’’ in management of transplant patients with allograft dysfunction. Major pathologies have excellent outcome if timely and adequately treated. Mixed acute rejections have worst clinical outcomes. http://dx.doi.org/10.1016/j.ijt.2015.09.003 Abstract #: ISOT2015-80 Changing spectrum of CMV disease. Is it the time for universal CMV prophylaxis? An experience at our center Sindhu Kaza, R. Dharshan, P. Ravindra, P. Shankar Kasturba Medical College, Manipal, India Background: Cytomegalovirus (CMV) is one of the most frequently encountered opportunistic viral pathogens in renal transplantation (RT). The spectrum of CMV infection ranges from latent infection to asymptomatic viral shedding to lifethreatening multisystem disease. Current KDIGO/ATS guidelines recommend that RTRs (except in D-/R-CMV serology) receive chemoprophylaxis for CMV infection with oral ganciclovir or valganciclovir for at least 3 months after transplantation and for 6 months after treatment. Aims: To study clinical profile, management and outcomes of cytomegalovirus disease (CMVD) after RT at our center before and after routine universal valganciclovir prophylaxis. Methodology: All patients who were diagnosed with post RT CMV disease from February 2014 to July 2015 were enrolled. Patients transplanted before January 2015 received valganciclovir prophylaxis for 100 days only if they received induction with anti-thymocyte globulin (ATG) or had a CMV serology D +/R . All patients transplanted after January 2015 received universal chemoprophylaxis with valganciclovir for 100 days and for 200 days if they received induction with ATG. CMVD was diagnosed if CMV infection was accompanied by clinical signs and symptoms. For analysis, patients were divided into three groups: Patients with (1) late CMV disease (>1yr posttransplant), (2) early CMV disease (<1 yr post-transplant) and (3) RTRs' after January 2015. Their clinical and immunosuppression details, treatment, response, outcomes were evaluated. Results: Out of 8 cases of CMVD diagnosed during the study period three cases belonged to group 1, five to group 2 and none in group 3. 31 patients received live RT during the study period, out of which 11 patients were transplanted after February 2015 and received universal prophylaxis with valganciclovir. All patients had D+/R+ pre-transplant CMV serology and mean CNI levels were within normal range at the time of diagnosis of CMVD. Only 2 out of 8 patients received induction (basiliximab). In group 1 all patients were on CSA/AZA/Steroids with mean duration for post-transplant CMVD being 8years. They had predominant extra renal manifestations with no leucopenia. 2 out of 3 patients had CMV diagnosed on histopathology with negative blood CMV DNA PCR. All of them responded well to anti-CMV treatment with good patient outcomes. In group 2 all patients were on TAC/MMF/Steroids with mean duration for CMVD being 72 days post-transplant. Most common presentation was leucopenia, severe CMVD and life. Conclusions: The incidence of CMV disease was 41.6% in patients with no/basiliximab induction. Early CMVD had a high incidence of life threatening opportunistic pathogens resulting in a very high mortality (80%). Late CMVD had milder nonleucopenic extra renal disease with improved patient outcomes. http://dx.doi.org/10.1016/j.ijt.2015.09.004
Abstract #: ISOT2015-89 A cross-sectional study of renal donors D. Shivakumar, P. Abeesh, C. Vasudevan, S. Ilango, V. Balaraman Government Kilpauk Medical College, Chennai, India Background: In India, for renal transplant program, the donor pool is mainly from living related donors. The evaluation of donor is done meticulously to ensure he/she is healthy and fit for donation. Also it is made sure that the donor is not at increased risk of renal disease in the future. After donating a kidney, the remaining kidney increases its function to compensate for its lost pair. We in this study evaluated donors of our institute after kidney donation. Aims: To assess for new onset proteinuria, anaemia, hypertension and diabetes during post donation period and the current renal function status of donors & to compare eGFR with GFR measured by DTPA renogram. Methodology: This cross sectional study done during August 2013 to February 2014 included renal donors of minimum of 3 months post donation. Their histories and previous medical records were reviewed and they were meticulously examined. They underwent urine analysis including spot PCR (Protein Creatinine ratio), complete blood count with peripheral smear study and their fasting blood sugar (FBS) was tested. Renal function was assessed by serum creatinine (Modified Jaffes' method) and GFR was estimated using Cockcroft–Gault (CG) formula, MDRD and CKD EPI creatinine equations. Estimated GFR derived through the above formulae were compared with GFR measured by 99mTc-DTPA renogram method so as to assess the utility of these equations in our study population. Renal imaging done by ultrasonography and renal size was noted. All the results and observations were compared and analyzed with their pre donation data. Statistical analysis was done using SPSS version 19.0. Results: Out of 30 renal donors 22 (73.3%) were females and 73.3% (22/30) of the donors were in the fourth and fifth decade. During the median period of 29 months (4–150 months) post transplant, there was neither significant raise in proteinuria, nor significant fall in haemoglobin. No significant variation in both systolic and the diastolic blood pressure. Though donors had significant raise in fasting blood sugar profile (84.50 vs. 91.90 p = 0.001), none of them developed frank diabetic status. There was significant fall in GRF estimated by all the three equations. GFR measured by 99mTc-DTPA renogram method also showed significant fall. The remnant kidney mean surface area was increased significantly (4082.8 vs. 5082 mm2, p = 0.001). There was significant increase in the GFR of the remnant kidney during post donation period (50.87 vs. 80.77 ml/mt, p = 0.001). None of the equations for estimating GFR had significant correlation with GFR measured by DTPA during both pre and post donation period. Conclusions: There was significant raise in new onset impaired fasting glucose among donors in post donation period. There was significant increase in mean surface area and GFR of remnant kidney. None of the equations for estimating GFR had significant correlation with GFR measured by DTPA in our study group. http://dx.doi.org/10.1016/j.ijt.2015.09.005
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/ijt
Abstract Oro-Poster Abstract #: ISOT2015-59 One year survival analysis and factors predicting graft outcome in renal transplant recipients: A single centre experience G. Ragi Krishnan, Jacob George, Noble Gracious, M.K. Mohandas, Sajeev Kumar Department of Nephrology, Government Medical College, Trivandrum, India Background: Renal transplantation is regarded as the best treatment for patients with CKD. It improves the quality of life, reduces mortality, and offers a higher life expectancy when compared to dialysis. Most of the centres around the world report a short-term graft survival of 90–95%. There is paucity of data on graft and patient survival in renal transplant recipients from India. We present the one year survival analysis of renal transplants performed at our institution during last four and half years. Aims: (1) To analyze patient and graft survival in renal transplant recipients. (2) To analyze the association of factors predicting survival. Methodology: This is a observational, retrospective cohort study, including all the patients who underwent kidney transplantation in Government Medical College, Trivandrum from February 2nd, 2010 to July 31, 2015. All patients received triple drug immunosuppression. Patients in high risk group received induction therapy with IL-2 receptor blockers/ antithymocyte globulin. Demographic, clinical, laboratory, pretransplantation, and evolutionary clinical data after renal transplantation were obtained from patient records. Comparisons between the demographic and clinical characteristics of the patients who died and those of the patients who survived were conducted using the chi-squared (x2) test of association or, when indicated, Fisher's exact test. The Kaplan–Meier method was used for construction of survival curves. The Cox proportional hazards model was used for identification of factors associated to mortality and graft survival. Statistical analyses were conducted using SPSS software version 16. Results: A total of 126 transplants were done during the study period. Of this, 94 (74%) were males and 32 (26%) were females. 1 year patient survival was 91.8% and 1 year overall graft survival was 86%. Death censored graft survival was 94.1%. Functional graft survival was 91.7%. Death with functioning graft was the commonest cause of graft loss (33%). There were 4 cases of primary nonfunction, 3 cases of acute rejection and 3 were related to surgical complications. DGF was seen in 18 (14.2%) patients. There were 17 (13.5%) biopsy proven acute rejection (BPAR) episodes. Of these, 13 (77%) were antibody
mediated rejection and 6 (23%) were due to acute cellular rejection. 8.2% patients were lost, mainly due to infections. Primary graft nonfunction was noted in 2 patients (16%). Among risk factors for graft survival, rejection episodes, surgical complications and duration of HD prior to transplant were found to be significant. Conclusions: Our one year death censored graft survival rates (94%) are comparable with those reported from other international centres. Most common cause of graft loss was death with functioning graft followed by rejection and surgery related complications. http://dx.doi.org/10.1016/j.ijt.2015.09.002 Abstract #: ISOT2015-38 The study of incidence based graft biopsies performed in live renal allograft recipients Mukesh Goyal, U.N. Hegde, Sishir Gang, M.M. Rajapurkar, Kalpesh Gohel, Amit Jojera Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India Background: Several methods have been used to diagnose renal allograft dysfunction, including clinical evaluation and laboratory tests; however, core biopsy remains the ‘‘gold standard’’ for the diagnosis of renal transplant abnormality. Aims: To study the clinico-histopathological findings in the incidence based graft biopsies performed in live renal allograft recipients transplanted between 1st April 2013 and 31st December 2014. Methodology: Clinico-histopathological analysis with C4d immunostaining were performed on 167 needle core biopsies from 111 patients from live renal allograft recipients transplanted between and underwent incidence based graft biopsy between April 1, 2013 and December 31, 2014 at our center. Results: Major histological findings were normal pathology 34%, acute rejections 26%, CNI toxicity 11.3%, ATI 8.9%, pyelonephritis 3%, IFTA 4.7% and recurrence/glomerular disease was 1.7%. There was no major difference between various pathological groups as far as recipient and donor age, gender distribution, cold ischemia time, HLA mismatch, induction status, nonblood related donors and BMI was concerned. At 3 month post biopsy 60–80% incidences have shown recovery (complete or partial) across all histopathological groups except with histological features of mixed rejection (antibody mediated and cellular rejection) which shown recovery on only 33% incidences with highest incidence of graft function worsening (47%), graft and or patient loss (36%) and highest need for repeat biopsy (47%).
48
indian journal of transplantation 9 (2015) 47–60
Conclusions: Graft biopsy remains ‘‘gold standard’’ in management of transplant patients with allograft dysfunction. Major pathologies have excellent outcome if timely and adequately treated. Mixed acute rejections have worst clinical outcomes. http://dx.doi.org/10.1016/j.ijt.2015.09.003 Abstract #: ISOT2015-80 Changing spectrum of CMV disease. Is it the time for universal CMV prophylaxis? An experience at our center Sindhu Kaza, R. Dharshan, P. Ravindra, P. Shankar Kasturba Medical College, Manipal, India Background: Cytomegalovirus (CMV) is one of the most frequently encountered opportunistic viral pathogens in renal transplantation (RT). The spectrum of CMV infection ranges from latent infection to asymptomatic viral shedding to lifethreatening multisystem disease. Current KDIGO/ATS guidelines recommend that RTRs (except in D-/R-CMV serology) receive chemoprophylaxis for CMV infection with oral ganciclovir or valganciclovir for at least 3 months after transplantation and for 6 months after treatment. Aims: To study clinical profile, management and outcomes of cytomegalovirus disease (CMVD) after RT at our center before and after routine universal valganciclovir prophylaxis. Methodology: All patients who were diagnosed with post RT CMV disease from February 2014 to July 2015 were enrolled. Patients transplanted before January 2015 received valganciclovir prophylaxis for 100 days only if they received induction with anti-thymocyte globulin (ATG) or had a CMV serology D +/R . All patients transplanted after January 2015 received universal chemoprophylaxis with valganciclovir for 100 days and for 200 days if they received induction with ATG. CMVD was diagnosed if CMV infection was accompanied by clinical signs and symptoms. For analysis, patients were divided into three groups: Patients with (1) late CMV disease (>1yr posttransplant), (2) early CMV disease (<1 yr post-transplant) and (3) RTRs' after January 2015. Their clinical and immunosuppression details, treatment, response, outcomes were evaluated. Results: Out of 8 cases of CMVD diagnosed during the study period three cases belonged to group 1, five to group 2 and none in group 3. 31 patients received live RT during the study period, out of which 11 patients were transplanted after February 2015 and received universal prophylaxis with valganciclovir. All patients had D+/R+ pre-transplant CMV serology and mean CNI levels were within normal range at the time of diagnosis of CMVD. Only 2 out of 8 patients received induction (basiliximab). In group 1 all patients were on CSA/AZA/Steroids with mean duration for post-transplant CMVD being 8years. They had predominant extra renal manifestations with no leucopenia. 2 out of 3 patients had CMV diagnosed on histopathology with negative blood CMV DNA PCR. All of them responded well to anti-CMV treatment with good patient outcomes. In group 2 all patients were on TAC/MMF/Steroids with mean duration for CMVD being 72 days post-transplant. Most common presentation was leucopenia, severe CMVD and life. Conclusions: The incidence of CMV disease was 41.6% in patients with no/basiliximab induction. Early CMVD had a high incidence of life threatening opportunistic pathogens resulting in a very high mortality (80%). Late CMVD had milder nonleucopenic extra renal disease with improved patient outcomes. http://dx.doi.org/10.1016/j.ijt.2015.09.004
Abstract #: ISOT2015-89 A cross-sectional study of renal donors D. Shivakumar, P. Abeesh, C. Vasudevan, S. Ilango, V. Balaraman Government Kilpauk Medical College, Chennai, India Background: In India, for renal transplant program, the donor pool is mainly from living related donors. The evaluation of donor is done meticulously to ensure he/she is healthy and fit for donation. Also it is made sure that the donor is not at increased risk of renal disease in the future. After donating a kidney, the remaining kidney increases its function to compensate for its lost pair. We in this study evaluated donors of our institute after kidney donation. Aims: To assess for new onset proteinuria, anaemia, hypertension and diabetes during post donation period and the current renal function status of donors & to compare eGFR with GFR measured by DTPA renogram. Methodology: This cross sectional study done during August 2013 to February 2014 included renal donors of minimum of 3 months post donation. Their histories and previous medical records were reviewed and they were meticulously examined. They underwent urine analysis including spot PCR (Protein Creatinine ratio), complete blood count with peripheral smear study and their fasting blood sugar (FBS) was tested. Renal function was assessed by serum creatinine (Modified Jaffes' method) and GFR was estimated using Cockcroft–Gault (CG) formula, MDRD and CKD EPI creatinine equations. Estimated GFR derived through the above formulae were compared with GFR measured by 99mTc-DTPA renogram method so as to assess the utility of these equations in our study population. Renal imaging done by ultrasonography and renal size was noted. All the results and observations were compared and analyzed with their pre donation data. Statistical analysis was done using SPSS version 19.0. Results: Out of 30 renal donors 22 (73.3%) were females and 73.3% (22/30) of the donors were in the fourth and fifth decade. During the median period of 29 months (4–150 months) post transplant, there was neither significant raise in proteinuria, nor significant fall in haemoglobin. No significant variation in both systolic and the diastolic blood pressure. Though donors had significant raise in fasting blood sugar profile (84.50 vs. 91.90 p = 0.001), none of them developed frank diabetic status. There was significant fall in GRF estimated by all the three equations. GFR measured by 99mTc-DTPA renogram method also showed significant fall. The remnant kidney mean surface area was increased significantly (4082.8 vs. 5082 mm2, p = 0.001). There was significant increase in the GFR of the remnant kidney during post donation period (50.87 vs. 80.77 ml/mt, p = 0.001). None of the equations for estimating GFR had significant correlation with GFR measured by DTPA during both pre and post donation period. Conclusions: There was significant raise in new onset impaired fasting glucose among donors in post donation period. There was significant increase in mean surface area and GFR of remnant kidney. None of the equations for estimating GFR had significant correlation with GFR measured by DTPA in our study group. http://dx.doi.org/10.1016/j.ijt.2015.09.005