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   Table of Contents - Current issue
July-September 2019
Volume 13 | Issue 3
Page Nos. 151-235

Online since Tuesday, September 17, 2019

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Twenty-five years of transplantation law in India – Progress and the way forward Highly accessed article p. 151
Sunil Shroff
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Transplantation in C3 glomerulopathy – Damned if you do, damned if you don't p. 154
Srikanth Gundlapalli, Suhas Dilip Mondhe
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Granulomatous interstitial nephritis in native kidneys and renal allografts p. 156
Praveen Kumar Etta
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Postrenal transplant anemia and pure red cell aplasia p. 160
Praveen Kumar Etta
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Significance and safety of renal allograft biopsies: Experience from a tertiary care center in India p. 164
Nisha Gaur, Vinay Malhotra, Dhananjai Agrawal, Shailendra K Singh, Pankaj Beniwal, Sanjeev Sharma, Rajesh Jhorawat, Parvati Joshi, Shikha Khandelwal, Vartul Gupta
Introduction: Renal allograft biopsy is a useful tool in the presence of allograft dysfunction. There are many published studies regarding utility and safety of native kidney biopsies, whereas for allograft biopsies, data are scarce. Methodology: This retrospective analysis included all patients who underwent renal allograft biopsies from January 1, 2012, to December 31, 2017. Data were collected from patient records and interviews. Details regarding clinical indications, preprocedure rise in creatinine, urine analysis, periprocedure fall in hemoglobin, postprocedure hematoma in ultrasonography, and other complications were noted. Details of biopsy findings were analyzed. We noted the changes made in treatment after renal biopsies. Results: One hundred and seventeen (n = 117) patients underwent 150 renal biopsy procedures, with a mean age of 38.3 ± 11.6 years. Ninety-two (78.6%) were male. The majority (89.74%) of the patients received kidney from live donors. The most common indication for biopsy was acute allograft dysfunction (54%) with asymptomatic rise in creatinine (32.7%). In the first 15 days posttransplantation, the most common indication was delayed graft function (15.33%). Ninety percent of biopsies were adequate. For clinical diagnosis of acute allograft dysfunction, the most common pathological finding was active antibody-mediated rejection (AMR) in 14.49% patients. In the presence of chronic allograft dysfunction, the most common histopathological finding was chronic AMR in 18 (13.04%) biopsies. Major complications occurred in 4.0% of patients. Conclusion: Renal allograft biopsy is a useful tool in the evaluation of allograft dysfunction, and with current biopsy technique under real-time sonography, the major complication rate is less. It can be regarded as a safe procedure with excellent diagnostic yield.
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Is the Institute Georges Lopez-1 solution an equally effective, cheaper alternative to the University of Wisconsin solution in liver transplantation? p. 169
Magnus Mansard, Ravichand Siddachari, Sanjay Govil, Suresh Doraiswamy, Goutham Kumar, Navaneethan Subramanian, Olithselvan Arikichenin
Aim: To compare the outcomes of deceased donor liver transplantation (DDLT) using either the University of Wisconsin solution (UW) or the Institute Georges Lopez-1 (IGL-1) solution. Materials and Methods: Adult patients who underwent DDLT between November 2015 and March 2018 were included in the study. All patients received grafts from brain-dead donors. In 30 patients, the UW solution was used to preserve the liver and in 53 patients, the IGL-1 solution was used. The data of these two groups of the patients were analyzed and compared. Results: Between the two groups of patients, donor and recipient demographics and surgery-related variables were found to be similar. No difference was observed in the incidence of postreperfusion syndrome, number of days of hospitalization, and in the 30-day mortality. Early graft dysfunction was observed in 9 (16.98%) patients in the IGL-1 group and in 7 (23.33%) patients in the UW group (P = 0.48). One patient had primary nonfunction in each group. The postoperative levels of the liver transaminases were also not found to be significantly different. Conclusions: The efficacies of liver preservation by the IGL-1 and UW solutions were found to be comparable.
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Did an increase in knowledge and awareness about organ donation improve organ donation rate in India over the past two decades? p. 173
Ann Alex, Sunil Shroff, V Britzer Paul, Sumana Navin, Pavithra Ramesh, John Michael, Susmitha Menon
Context: The growth in the solid organ transplant has not been able to keep pace with the global requirement for organs, with great differences among countries. No previous studies about public awareness related to organ donation over two-decades have been conducted. Aim: The paper focuses on studying the difference in the knowledge and attitude among the Indian public about organ donation, over two decades. The study further probes into the impact that public knowledge has on organ donation rates. Settings and Design: This is a cross-sectional study conducted from 1998 to 2017. The first 10 years of the study (Group-I) was administered physically, whereas in the next 10 years (Group-II) online tools were used to conduct the survey. The total number of respondents in the two decades was 3914. Subjects and Methods: It contained a structured questionnaire with ten multiple choice questions and basic demographic details. The survey questions were the same for both the periods of the study. Statistical Analysis Used: The data entered was analyzed using SPSS v. 19. The knowledge on organ donation was compared between the two decades and if in any increase in awareness was reflected in the organ donation rate. Results: The increase in awareness on the organs and tissues that can be donated was high among Group-II and it was statistically significant (P < 0.001). More importantly, the proportion of respondents who were aware about the “organ donor card” more than doubled from 23.7% in Group I to 63.7% in Group II; and this was statistically significant (P < 0.001). The deceased donation rate was 0.08 per million population in 2004, whereas it had increased to 0.34 pmp in 2014 and 0.8 pmp in 2016. Conclusions: There has been an increase in awareness in the two decades, and this is also reflected in an increase in the donation rate in the country. Creating more awareness can be one of the factors to increase the organ donation rate in India.
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Graft function and outcomes of deceased donor kidney transplant patients in a tertiary care center p. 179
Sujit Surendran, M Edwin Fernando, S Thirumavalavan, S A. K Noor Mohamed, P Senthil Kumar
Introduction: In India, deceased donor kidney transplantation accounts for less than 1% of total kidney transplants that are performed each year. Objectives: To assess the outcomes of deceased donor kidney transplantation. Methodology: We retrospectively reviewed deceased donor kidney transplantation in our centre from January 1996 to March 2016. All recipients were followed to the point of graft loss or death. Results were analysed in terms of age of donor and recipient, graft ischemia time, graft function,discharge serum creatinine, any rise in serum creatinine during follow up, post transplant complications, graft and recipient survival. Results: A total of 105 kidney transplant recipients including 81 men (77.14%) and 24 women (22.85%) were included in our analysis. The one year recipient survival rate was 75.8% and one year graft survival was 89.58%. The graft rejection rates were 18% in our centre and the mortality rate was 27.6%. Conclusions: By minimizing ischemia times, using better perfusion techniques and optimized immuno suppresion deceased donor transplant outcomes can be improved.
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Posttransplant vesical calculi – A case series p. 184
Dimple Kumar Chanamolu, Ravi Koti Reddy Kolatham, T Narendar, V L. N Murthy Pisapati
Background: The occurrence of posttransplant vesical calculi is rare. Suture material, used during ureteroneocystostomy, both absorbable and nonabsorbable have been implicated as the nidus for stone formation. We report five cases of renal transplant recipients, who developed vesical calculi several years after renal transplantation, and the nidus was the prolene suture. Methods: Between 1997 and 2010, 344 renal transplants were performed which included both cadaver and live-related transplantations. The ureteroneocystostomy was performed by modified Lich-Gregoir technique using 6–0 prolene as the suture material. All cadaver transplants and some of the live cases were stented. The Foley catheter was removed between 3 and 5 days, and DJ stent was removed between 4 and 6 weeks postoperatively. Standard triple drug immunosuppression was given and followed up at regular intervals. Results: Five patients developed small vesical calculi between 10 and 21 years after transplantation at the site of ureteroneocystostomy, and prolene suture was the nidus. There were three ureteric leaks postoperatively, two were due to ureteric necrosis requiring reconstruction, and one was due to anastomotic leak which subsided on prolonged bladder drainage. There was one case of ureteric obstruction in the immediate postoperative period which was stented. Conclusion: Nonabsorbable suture material, however fine it is, prompts stone formation in the long run and should be avoided during ureteroneocystostomy.
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Deceased donor transplantation – Our experience in the last 4 years p. 188
Vilesh Valsalan Kalthoonical, Georgy K Nainan, George P Abraham, Mohan Mathew, Datson George, Renu Paul, YS Sooraj, Philip G Thomas, Vijay Radhakrishnan, Francis C Manavalan
Background: Kidney transplant is the best treatment option for end stage kidney disease. Deceased donor transplantation has helped in increasing the donor pool for waitlisted dialysis patients. We received seventy deceased donor kidneys through the Kerala Network of Organ Sharing (KNOS) over the past 4 years from August 2013 to August 2017 and transplanted sixty six with good outcome. Pre-implantation biopsy performed in marginal donors helped in decision making to take the kidney and increase the donor pool. Aims and Objectives: 1)To evaluate outcome of renal transplant recipients in deceased donor transplantation. 2)To evaluate the role of pre-implantation biopsy to improve donor selection for better long term outcome. Materials and Methods: Sixty-six deceased donor kidneys were transplanted into the recipients from our pool of 253 patients registered with the KNOS. Four cadaver kidneys were rejected based on pre-implantation biopsy. Fifty-nine transplants were done at VPS Lakeshore and seven were done at PVS Memorial Hospital, Kochi. Donors of age less than 65 years were considered. Pre-tranpslant evaluation of recipients on waiting list including lab and cardiac evaluation with PRA status was done. Cross match was done prior to transplant. Triple immunosuppression including cyclosporine, mychophenolate mofetil and prednisolone with basiliximab as induction agent was used in all cases. Low dose tacrolimus was introduced after the third month in some cases. Pre-implantation biopsy was done in marginal donors for better donor selection. Results: Of the 66 recipients, 52 (78.8%) were males and 14 (21.2%) were females. PRA status was negative in all recipients. Deceased donors <65 years of age were considered. Twenty deceased donor kidneys were biopsied before implantation, of which 16 were implanted. Four kidneys were rejected as one showed glomerulocystic changes . One had extensive thrombus in all glomeruli, one had >56% IFTA changes, and other had 30%–40% IFTA changes. Results at 4 years post-transplant showed graft survival in 55/66 (83.34%) and patient survival in 60/66 (90.91%) cases. Six patients died: two with pneumocystis carinii pneumonia (PCP) (at 9 months/3.3 years post-transplant), one with mucormycosis (at 16 months post-transplant), one with acute coronary syndrome (immediate post-transplant), and two patients with sepsis. The average serum creatinine was < 1.4 mg/dl in 48 (87.2%) cases, 1.4–2.4 mg/dl in 7 (12.7%) cases, and > 2.4 mg/dl in 1 (1.8%) case. The surgical outcome was good in all (100%) patients with no intraoperative surgical complications. Delayed graft function was noted in 18% of patients. Prolonged cold ischemia time was noted in patients with acute tubular necrosis. Six patients had acute rejection, of which two were antibody mediated, and four had acute cellular rejection. One patient had tacrolimus toxicity on biopsy and was shifted to everolimus. Infections included one patient with surgical wound infection, 12 patients with urinary tract infections, one patient with invasive fungal infection, and two patients with PCP. At 4 years, deceased donor transplantation has good graft and patient outcomes. Conclusion: Deceased donor transplantation has good graft outcome which is comparable to live non related donors. It has minimal paper work and less costly than routine live transplant. Pre-implantation biopsy should be considered in marginal donors for appropriate donor selection and avoid organ wastage in doubtful cases. In our study we noted that transplant outcome was better in recipients receiving kidney from with in the city limits because of less cold ischemia time. Hence facilities for early transportation of organs with minimal procedural hurdles to minimize cold ischemia time should be carried out by the concerned authorities. Proactivity from the Government at state, zonal and national level is needed to improve deceased donor pool and cadaver transplantation in India.
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Barriers and suggestions towards deceased organ donation in a government tertiary care teaching hospital: Qualitative study using socio-ecological model framework p. 194
Britzer Paul Vincent, Gunjan Kumar, Sreejith Parameswaran, Sitanshu Sekar Kar
Background: Although the science of transplant has grown, its complementary field “organ donation” is still in its infancy stage in India. There have been very few center-based studies to understand the barriers toward organ donation in a government hospital. Moreover, all of those few studies were from an objectivist point of view and were not subjectivist in approach. Aim: Therefore, this study aims to understand the subjective views on barriers in the process of deceased organ donation among the stakeholders and their suggestions to improve in a government hospital's transplant unit. Methods: Qualitative (subjectivist) method was undertaken to attain the aim of the study and was analyzed using the socio-ecological model (SEM). In-depth interviews were carried out with stakeholders such as nephrologist, urologist, transplant coordinator, a transplant nurse, donor family, and an organ recipient. Results: Each level of the SEM played a vital role in the process of organ donation and they were interwoven with each other. The barriers toward the process of deceased organ donation were mistrust on the health care, unknown will of the deceased, poor communication, interfering of untrained professionals during grief counseling, family background, and lack of incentives and support toward the deceased organ donation program from the administrators. Conclusion: It is worthy to consider the process of organ donation from a Multi-disciplinary viewpoint in planning for future policies, interventions, and research. It is essential to conduct qualitative research to understand more about the barriers toward the practice of organ donation from the service receiver's and provider's perspective.
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Utility of induction agents in living donor kidney transplantation p. 202
Radhika Chemmangattu Radhakrishnan, Gopal Basu, Anjali Mohapatra, Suceena Alexander, Anna T Valson, Shibu Jacob, Vinoi George David, Santosh Varughese, Tamilarasi Veerasami
Aim: The outcome and long-term adverse events associated with induction agent use for living donor (LD) kidney transplantation (KT) in India were studied. Materials and Methods: Consecutive LD kidney transplant recipients (KTRs) from 2005 to 2013 were studied. They were divided based on induction agent use, into induction group and no induction group. The induction group was further subdivided into those receiving antithymocyte globulin (ATG group) and those receiving basiliximab (IL-2RB group). Study subjects were also classified into high and low immunological risk groups. Outcomes evaluated were patient and graft survival, acute rejections, infections, leucopenia, malignancy, new-onset diabetes mellitus, antibody-mediated rejections, and 1-year serum creatinine. Results: Of 605 LD-KTRs, 445 (73.6%) received induction. 403 (90.6%) received basiliximab induction. There was significant improvement in patient and graft survival in induction group (log rank P = 0.041 and 0.024, respectively), but this benefit disappeared when adjusting for immunosuppressive regimen as well as when only patients on tacrolimus-mycophenolate (Tac-MPA) were considered. There was significant reduction in acute rejections, tuberculosis (TB), and BK viremia in the induction group even in patients receiving Tac-MPA. There was no significant difference between basiliximab and ATG except for increased risk of BK viremia with ATG. Conclusions: The use of induction agents is associated with reduced incidence of acute rejections and serious infections (TB and BK viremia). The survival benefit of induction agent use is lost with the Tac-MPA-based immunosuppression. Thus, induction agent use is not essential for better survival if using Tac-MPA-based regimen.
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Incidence and risk factors for mortality in patients with cirrhosis awaiting liver transplantation p. 210
Mayank Jain, Joy Varghese, Chandan Kumar Kedarishetty, Vijaya Srinivasan, Jayanthi Venkataraman
Aim: This study aimed to determine the mortality in Indian patients awaiting liver transplantation and to assess the impact of cirrhosis-related complications (CRCs) on mortality. Materials and Methods: This was a prospective study on patients of Indian origin, aged >18 years, with cirrhosis liver (confirmed by imaging and/or liver biopsy), and registered for liver transplant (LTx) between November 2015 and May 2016. Patients were followed up for at least a year. Any admission or day-care procedure for complications after registration was recorded as an event, and outcome was noted as recovered, deterioration, or death. The primary end point of the study was LTx, survival, or death. Patients undergoing transplantation were grouped with survivors for analysis of factors predicting waitlist mortality. Statistics: t-test, Chi-square test, Mann–Whitney U-test, and univariate and logistic regression analyses were used for statistical analysis. P < 0.05 was considered statistically significant. Results: A total of 227 (72.3%) registered patients survived. Waitlist mortality at 1 year was 27.7%, and the waitlist mortality rate was 33.8 deaths/100 patient-years. A significant proportion of nonsurvivors belonged to the Child–Turcotte–Pugh C score (P = 0.031), with higher Model for End Stage Liver Disease (P = 0.002) and greater frequency of CRC (P < 0.001). Hepatic encephalopathy (HE), renal dysfunction (RD), infection, and variceal bleeding were significantly associated with death. A higher proportion of nonsurvivors had combination of more than two CRCs. Conclusion: The waitlist mortality was 27.7%. Complications such as variceal bleed, spontaneous bacterial peritonitis, HE, and RD were significantly high in nonsurvivors.
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Renal transplantation in bilateral iliac vein thrombosis: A difficult case scenario p. 216
Debayan Banerjee, Tarshid Ali Jahangir, Tapas Kumar Saha, Anup Dutta Baruah
A case of end-stage renal disease with bilateral iliac vein thrombosis underwent renal transplantation at our institute. Right external iliac vein (EIV) is the common site for anastomosing renal vein during renal transplantation. Patients undergoing repeated venous access for hemodialysis particularly femoral venous cannulation, have iliac vein thrombosis which we encounter during transplant workup. A 51-year-old diabetic, hypertensive female with end-stage renal disease with a history of multiple arteriovenous fistulae and bilateral femoral venous cannulation was planned for renal transplantation. On evaluation, her right common iliac vein and left EIV showed diffuse narrowing in computed tomography angiography. The renal vein was anastomosed to the proximal part of the inferior vena cava and the stump of the renal artery anastomosed to the right common iliac artery. Creatinine showed gradual decline, and the patient was discharged home on the 10th postoperative day with serum creatinine value of 1.76 mg/dl.
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Primary cutaneous aspergillosis in a renal allograft recipient p. 219
Luvdeep Dogra, Manisha Sahay, Kiranmai Ismal, PS Vali, Anuradha K
Cutaneous fungal infection due to aspergillus is relatively less known. Mostly it occurs due to Aspergillus flavus. This entity should be included in differential diagnosis of cutaneous fungal infections
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Decision-making in complex clinical scenarios using an ethical framework: Kidney transplantation in a patient with severe left ventricular dysfunction p. 221
Sreejith Parameswaran, Suman Lata, Santhosh Satheesh, Manikandan Ramanitharan
Complex medical scenarios such as organ transplantation often bring up complex ethical issues for the medical practitioner. Knowledge about evidence-based medical evaluation and management combined with adhering to fundamental principles of medical ethics will go a long way in protecting the interests of all the stakeholders. Here, we discuss a complex scenario faced by our kidney transplantation team about offering transplantation for a patient with severe left ventricular dysfunction and how we used a framework of ethical principles in clinical decision-making.
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Successful treatment of isolated vascular arteritis in renal allograft recipients: A treatable new histological entity p. 225
Khandalvalli Pradeep, Manjusha Yadla, Megha Harke
C4d-negative isolated endarteritis is an entity yet to be recognized as an independent entity in Banff Classification. Pathogenesis and treatment of this entity are not well understood. Although it was identified as an entity similar to T-cell rejection based on the response to T-cell depletion therapies in a large retrospective study, this observation is yet to be supported in molecular experimental studies.
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Renal transplant in a patient with idiopathic thrombocytopenic purpura refractory to steroid and intravenous immunoglobulin p. 228
Shubham Agarwal, Pankaj Beniwal, Dhananjai Agarwal, Vinay Rathore
Chronic kidney disease in immune thrombocytopenia (ITP) is uncommon, and renal transplant in this setting is especially rare. We present a case of successful renal transplantation in a patient with chronic ITP refractory to steroid and intravenous immunoglobulin (IVIg). A 27-year-old female suffering from ITP was referred to our center for renal transplant with her mother as a donor. Her platelets count failed to improve despite treatment with prednisolone (1 mg/kg/day for 4 weeks) and IVIg (1 g/kg/day for 2 consecutive days). She was then treated with eltrombopag (50 mg/day), a thrombopoietin receptor agonist, following which her platelet counts improved and allowed kidney transplantation to be performed safely. At 1 year of follow-up, her graft was functioning normally. The case report highlights that renal transplantation is feasible in patients with ITP, even if the disease is refractory to first-line agents. Eltrombopag may be used to increase the platelet count and decrease the risk of bleeding during the peritransplant period.
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Antibody-mediated pure red cell aplasia after treatment with darbepoetin-alpha postrenal transplantation p. 231
Badarinath Vellaboina, Ravishankar Bonu, Topoti Mukherjee, Rohan Augustine
Pure red cell aplasia (PRCA) is a rare normochromic, normocytic anemia with a near-to-complete absence of erythroblasts in the bone marrow. Erythropoiesis-stimulating agents have been used widely to improve anemia in patients with chronic kidney disease. We present a case of a 38-year-old woman who was detected to have anemia (hemoglobin: 10 g/dl) and renal dysfunction (creatinine: 3 mg/dl) on a routine health check in December 2016. Her kidney biopsy showed chronic interstitial nephritis. She received intravenous (IV) iron and was started on darbepoetin-alpha. Her hemoglobin after 3 months of treatment was 12 mg/dl. She underwent preemptive one haplomatch renal transplantation on June 2017. She was discharged with serum creatinine of 0.9 mg/dl and hemoglobin of 8 g/dl. She was not on any Erthropoietin stimulating agents (ESA) at discharge. In the 4th week after transplant, her hemoglobin dropped to 7 g/dl, and she was restarted on darbepoetin-alpha 40 μg subcutaneously once a week. In the 6th week posttransplant, her hemoglobin dropped to 6 g/dl. Her peripheral smear showed normocytic normochromic anemia with no evidence of hemolysis. Transferrin saturation was 81%, serum ferritin levels were 1812 ng/ml, and reticulocyte count was 0.1%. Bone marrow biopsy showed suppression of erythroid precursors with myeloid-to-erythroid ratio of 8:1, adequate iron stores, and normal white blood cell and platelet precursors with no dysplastic cells. Paroxysmal Nocturnal hemoglobinuria (PNH) workup; antinuclear antibody; and screening for hepatitis B, hepatitis C, HIV, CMV, and human parvovirus B19 were negative. Anti-erythropoietin (EPO) antibody by enzyme-linked immunosorbent assay was positive. She was diagnosed to have PRCA secondary to anti-EPO antibodies. She was managed with pulse doses of methylprednisolone, adequate dose of tacrolimus, IV immunoglobulin of 125 g (2 g/kg) over 5 days, and two packed red cell transfusions. Darbepoetin-alpha was stopped. At present, her hemoglobin is 12.5 g/dl with serum creatinine of 1 mg/dl on triple immunosuppression with no requirement of ESA.
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Successful renal transplantation in a patient with perinuclear antineutrophil cytoplasmic antibody-associated vasculitis with chronic kidney disease with complement-dependent cytotoxicity crossmatch positivity (autoantibody induced) and donor-specific antibodies and flow cytometry crossmatch negative p. 234
GS Kasat, JC Patel, MV Patil, DP Kumar, VB Kute, PR Shah, HV Patel, PR Modi, VR Shah, VB Trivedi, HL Trivedi
The positive complement-dependent cytotoxicity crossmatch (CDCXM) is considered as a contraindication for renal transplantation (RT) since long in an effort to avoid immediate rejection. There has been tremendous development in our understanding of transplant immunology today, and more sensitive and specific methods such as flow cytometry crossmatch (FCXM) and solid-phase antibody screening are used for detailed immunological assessment. We report successful RT in a 23-year-old girl with end-stage renal disease due to vasculitis on dialysis for 2 years. Before transplantation, the patient had Anti Human Globulin CDCXM positive while Dithioerythritol (DTT)-CDCXM was negative. The patient had no donor-specific antibodies examined by Luminex single-antigen beads and her FCMXM was negative. In the posttransplant period, there was no evidence of immune injury. Her serum creatinine was 0.7 mg/dl on the 3rd posttransplant day at the time of discharge. Induction immunosuppression was rabbit thymoglobulin (1.5 mb/kg) and methylprednisolone (500 mg, 3 doses) and maintenance immunosuppression was tacrolimus + prednisolone + mycophenolic acid. We found that even though CDCXM positivity has been traditionally considered as a contraindication for renal transplantation, in few carefully selected patients, we can still proceed to renal transplantation even if CDCXM is positive if more advanced and robust immunological tools such as FCMXM and donor-specific antibodies are negative. In our patient, AHG-CDCXM was positive while DTT-CDCXM was negative making it clear that antibodies of IgM origin were probably responsible for CDCXM positivity.
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