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Table of Contents
April-June 2021
Volume 15 | Issue 2
Page Nos. 91-187
Online since Wednesday, June 30, 2021
Accessed 25,127 times.
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EDITORIAL
The ethical and moral compass of directed deceased donation
p. 91
Urmila Anandh, Manisha Sahay
DOI
:10.4103/ijot.ijot_3_21
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ORIGINAL ARTICLES
Prevalence of posttransplant anemia in patients undergoing renal transplantation at a tertiary care center in Kerala - A prospective observational study
p. 93
Surabhi Talwar, Rajesh Nair, Sandeep Sreedharan, Anil Mathew, Zachariah Paul, George Kurian
DOI
:10.4103/ijot.ijot_41_20
Background:
Studies on posttransplantation anemia (PTA) are scarce. There is a large variability in its prevalence (20%–70%). Research focuses on anemia in early (3–6 months) or late (>6 months) posttransplant period. Little is known about PTA within first 3 months.
Aim:
The aim of the study was to determine the prevalence and possible associated factors of immediate PTA in patients undergoing renal transplant.
Materials and Methods:
This was a prospective, observational, single-center study of 30 consecutive patients who underwent live renal allograft transplant. Follow-up period was 3-month posttransplant. Hemoglobin (Hb) was done at 1-week and 1, 2, and 3-month posttransplant. Erythropoietin (EPO) levels were recorded pre and posttransplant. Peripheral smear, lactate dehydrogenase, iron and ferritin levels, serum creatinine, days of hospital stay, rejections, infections, and immunosuppressive regime were recorded.
Results:
All patients were anemic within 1 week of transplantation and 40% had severe anemia. The prevalence of PTA at 3 months was 76.7%. PTA correlated with higher donor age, lower ferritin, Hb, and EPO levels in pretransplant period. However, even though EPO levels posttransplant were lower in patients with anemia, this correlation was not statistically significant. The lowest Hb correlated with Hb levels and dose of EPO-stimulating agents pretransplant.
Conclusions:
The prevalence of anemia is high in the immediate posttransplant period. High donor age, graft dysfunction, and iron stores before transplantation correlate with Hb levels at 3 months. It is prudent to maintain a better Hb in the pretransplant period to avoid PTA. Lower EPO levels before transplant may indicate immediate PTA. Correlation of EPO levels posttransplant with Hb needs further study.
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Evaluation of screening tests for pre-transplant compatibility testing in live-related kidney transplants: Single-center report from India - A prospective observational study
p. 99
Rajni Chauhan, Aseem Kumar Tiwari, Chhavi Rajvanshi, Simmi Mehra, Geet Aggarwal, Shyam Bihari Bansal, Vijay Kher
DOI
:10.4103/ijot.ijot_76_20
Introduction:
Pre-transplant compatibility testing involves the use of different methodologies (cell-based and solid phase based) for the determination of anti-human-leukocyte antigen (HLA) antibodies. Implementation of these donor-recipient methods in the screening of patients awaiting transplantation increased their chance of successful graft and patient outcomes.
Materials and Methods:
A total of 1054 patients visiting tertiary care hospitals for pretransplant compatibility testing were screened with cell-based tests; complement-dependent cytotoxicity crossmatch (CDC-XM) and flow cytometric crossmatch (FC-XM). The patients positive for either or both screening tests were suspected to have anti-HLA antibodies. Luminex single-antigen bead (SAB) tests were performed in such patients to determine and identify antibody specificity and establish donor-specific antibody (DSA).
Results:
The study showed a significantly higher sensitivity of the FCXM (94.6%) method when compared with CDC-XM (35.7%), considering the SAB assay as the gold standard technique. The specificity of CDC-XM (100%) was slightly higher than the FC-XM (76.3%). Combination of FC-XM with CDC-XM (17 cases) was 100% sensitive and specific to identify DSA (s). The graft-survival was 94.77% using the proposed algorithm.
Conclusions:
The combination of CDC-XM and FC-XM, along with SAB assay, could be used as a screening algorithm as it is a useful technique in identifying the specificities of alloantibodies, assessment of DSAs. Hence, the presented algorithm can become a new standard for the identification of potential recipients awaiting kidney transplantation in India.
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Evaluation of alternate-day valganciclovir prophylaxis for cytomegalovirus disease prevention in moderate risk renal transplant patients: A retrospective observational study
p. 104
Puneet Bhuwania, Ilangovan Veerappan, Ramaswami Sethuraman
DOI
:10.4103/ijot.ijot_84_20
Background:
Despite valganciclovir (VGCV) being the recommended agent for Cytomegalovirus (CMV) disease prevention, its optimal dose that maintains parity between the efficacies, toxicity profile, and most importantly, the cost has yet to be established. This study is the first to evaluate alternate day versus daily dose of VGCV prophylaxis in CMV prevention in moderate risk renal transplant patients (RTR).
Materials and Methods:
A single center, retrospective analysis of ninety-nine moderate risk RTR was done. The study participants received VGCV 450 mg/day (
n
= 49) versus VGCV 450 mg on alternative days (
n
= 50) for 90–100 days; as a prophylactic strategy against CMV disease. The primary endpoint was CMV disease incidence at 6 months. Graft survival, biopsy-proven rejection, hematological adverse events, opportunistic infections (OIs), and mortality have also been evaluated.
Results:
CMV disease occurrence at 6 months was zero in both the groups. Immunosuppression (induction and maintenance) were alike in both the groups except for higher tacrolimus trough levels in the 2
nd
month (
P
= 0.023) and lower mycophenolate acid area under curve levels in alternate-day group (
P
= 0.046). No difference was noted in biopsy-proven rejection, graft loss, mortality, and OIs, but leukopenia was more in patients receiving daily VGCV (
P
≤ 0.001), a multivariate logistic regression revealed a higher incidence of leukopenia in the daily group (
P
= 0.02; odds ratio, 13.6, 95% confidence interval 1.51–122.37).
Conclusions:
Alternate-day VGCV dosing provides similar efficacy as daily dosing in CMV prevention in D+/R + RTR with reduced leukopenia incidence and significant cost-benefit.
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Role of intravesical granulocyte-macrophage colony-stimulating factor in controlling hemorrhagic cystitis in patients undergoing stem cell transplantation - A retrospective cohort study
p. 111
Akanksha Garg, Roshni Dasgupta, Sandip Shah, Kinnari Patel, Kamlesh Shah
DOI
:10.4103/ijot.ijot_93_20
Introduction:
Hemorrhagic cystitis (HC) is a well-known complication in patients undergoing hematopoeitic stem cell transplantation (HSCT), contributing considerably to morbidity and prolonged hospital stay. Granulocyte-macrophage colony-stimulating factor (GM-CSF) affects the proliferation and differentiation of hematopoietic stem/progenitor cells and the functioning of monocytes, granulocytes, lymphocytes, and endothelial cells. The objective of this study was to evaluate the efficacy and safety of GM-CSF bladder irrigation for HC post-HSCT.
Materials and Methods:
We conducted a retrospective cohort study to assess the clinical effects of GM-CSF (GM-CSF group) in controlling HC in patients who had undergone HSCT at our institute. We also compared these patients with those who did not receive GM-CSF.
Results:
There were 12 patients in the GM-CSF group and seven patients in the non-GM-CSF (control) group. The median ages were 16 years (range: 4–33 years) and 19 years (range; 6–41 years), respectively. Median time-to-resolution of HC from day of onset was 9.5 days in the GM-CSF group versus 59 days in the non GM-CSF group (
P
= 0.001). Mortality was 85% in the control group as compared to 16% in GM-CSF group (
P
= 0.008). Among the GM-CSF responders, complete response was seen in eight patients (67%). None of the patients developed any systemic or local side effects to GM-CSF. Overall survival in the two groups was 75% and 14%, respectively (
P
= 0.043).
Conclusion:
GM-CSF was shown to be effective in controlling HC in post-HSCT patients, without any major side effects, along with decreased mortality and improved overall survival.
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Raoultella terrigena
infections in hematopoietic stem cell transplant recipients: High rate of mortality in multidrug-resistant strains - A retrospective observational study
p. 118
Ameni Mellouli, Yosra Chebbi, Anis Raddaoui, Rym El Fatmi, Saloua Ladeb, Tarek Ben Othmen, Wafa Achour
DOI
:10.4103/ijot.ijot_99_20
Background:
Raoultella terrigena
is a Gram-negative bacterium mainly reported as aquatic and soil organism. It is rarely involved in human infections. This study investigated the epidemiology of
R. terrigena
infections in the National Bone Marrow Transplant Center of Tunis (NBMTC) between January 2010 and March 2018, their associated antibiotics resistance patterns, and the molecular features of extended-spectrum β-lactamase (ESBL) producing strains.
Materials and Methods:
Our retrospective study concerned hematopoietic stem cell transplant (HSCT) adult recipients hospitalized at the NBMTC and infected with
R. terrigena
. The search of the ESBL and carbapenemases genes for multidrug-resistant strains was performed by PCR amplification.
Results:
Twelve strains of
R. terrigena
were responsible for infections in 10 hematopoietic stem cell transplant recipients (1.2% of total HSCT recipients). They were responsible for skin (
n
= 4) and urinary tract infections (
n
= 4). The first-line antibiotherapy was based on a monotherapy in one case and a dual therapy in eleven cases. Imipenem was the most prescribed antibiotic (
n
= 7/12). Mortality was attributable to
R. terrigena
infection in two over ten patients. Nine strains were producing ESBL. Five strains were resistant to ertapenem, two to imipenem, ten to ciprofloxacin, and five to amikacin.
Bla
CTX-M1
,
bla
OXA-48,
and
bla
KPC
were found in seven, four, and one strains, respectively.
Conclusion:
Low prevalence of
R. terrigena
infections in HSCT recipients but high rates of attributable mortality and multidrug-resistant strains.
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Matched unrelated donor hematopoietic stem cell transplantation: Roles and responsibilities of workup coordinator - An observational study
p. 122
Vikash Chandra Mishra, Dinesh Chandra, Nikki Dey, Amit Kr Bhardwaj, Archana Anthwal, Vimarsh Raina
DOI
:10.4103/ijot.ijot_120_20
Background:
With only 25% chances of finding a human leukocyte antigen matched stem cell donor within the family, in case of minimal residual disease, the dependence on matched unrelated donor (MUD) is inevitable. With increasing awareness about the MUD stem cell registries, the numbers of registrations for voluntary stem cell donations are also increasing each day. A workup coordinator is a strong and the most crucial link in the MUD hematopoietic stem cell transplantation (HSCT) workup. The coordination between the stem cell registry and transplant center TC in need of a MUD HSCT workup is handled by a workup coordinator.
Aims and Objectives:
The aim here is to highlight key roles and responsibilities of workup coordinators, without whom it can be impossible to complete a MUD HSCT.
Materials and Methods:
We accessed the roles and responsibilities of workup coordinators via the MUSD HSCT workup assisted by Genebandhu from May 2012 to August 2020. The methodology mainly involved was electronic communication between stem cell registry/transplant center (TC)/donor center/collection center/patient/donor. All these activities of coordinators were closely observed to understand their roles, requirements, and responsibilities in detail.
Results:
The workup coordinator has been successfully involved in 33 MUD HSCT workups since its inception. Out of these, 18 were from international stem cell registries and 15 with TC s from India.
Discussion:
Workup coordinator acts like a catalyst during a MUD HSCT. Appropriate and timely exchange of information between the registry and the TC is managed by a coordinator.
Conclusion:
This study showed the crucial role, requirements, and responsibilities of the coordinators and their importance in MUD HSCT workups.
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Cytomegalovirus infection and kidney transplantation- A retrospective study of risk factors and long-term clinical outcome
p. 125
Aravinth Kumar Rajendiran, Dhanapriya Jeyachandran, Natarajan Gopalakrishnan, Venkatesh Arumugam, Dineshkumar Thanigachalam, Sakthirajan Ramanathan
DOI
:10.4103/ijot.ijot_116_20
Aim:
The aim was to study the clinical characteristics of postrenal transplant cytomegalovirus (CMV) infection and analyze its risk factors and its impact on graft and patient survival.
Materials and Methods:
We reviewed medical records of 739 renal transplant patients over 17 years (2002–2018). The demographic characteristics of patients were collected and compared with and without CMV infection. Multiple logistic regression analysis was done to identify risk factors for posttransplant CMV infection. Kaplan–Meier survival curve analysis was performed to analyze graft and patient survival by CMV infection.
Results:
The prevalence of CMV infection in our center was 12.4%. The most common presentation of CMV infection posttransplant is CMV syndrome. The use of antirejection therapy (hazard ratio [HR] 4.2, 95% confidence interval [CI] 2.6–6.9,
P
= 0.00), and new-onset diabetes after transplantation (NODAT) (HR 5.95, 95% CI 3.4–10,
P
= 0.00) was independently associated with postrenal transplant CMV infection. In Kaplan–Meier survival analysis, death-censored graft survival was significantly superior in patients without CMV infection/disease (CMV group: 55.4% vs. non-CMV group: 70.6% at 140 months
P
= 0.046). Patient survival was also significantly superior in patients without CMV infection (CMV group :59.8% vs. non-CMV group: 75.9% at 140 months
P
= 0.016).
Conclusions:
The use of antirejection therapy and NODAT are strong risk factors for developing CMV infection. Posttransplant CMV infection has a significant negative impact on graft and patient survival.
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SPECIAL ARTICLE
ISOT consensus statement for the kidney transplant recipient and living donor with a previous diagnosis of COVID-19
p. 131
Vivek B Kute, Sandeep Guleria, Anil K Bhalla, Ashish Sharma, Sanjay K Agarwal, Manisha Sahay, Santosh Varughese, Narayan Prasad, Prem P Varma, Sunil Shroff, Harsh Vardhan, Manish R Balwani, Shruti D Dave, Dhamendra Bhadauria, Manish Rathi, Dhananjai Agrawal, Pankaj R Shah, Jai Prakash
DOI
:10.4103/ijot.ijot_26_21
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REVIEW ARTICLES
Challenges of COVID-19 vaccination in the context of transplantation - A narrative review
p. 134
Hari Shankar Meshram, Vivek B Kute, Sanjay K Agarwal, Manisha Sahay
DOI
:10.4103/ijot.ijot_52_21
Coronavirus disease 19 (COVID-19) vaccination is imperative for preventing disease transmission and combating the associated mortality. Vaccination in the setting of transplantation is a complex issue. Owing to the chronic immunocompromised state in a transplant recipient, the immunogenicity of the vaccines is expected to be attenuated. Immunizing pretransplant patients will also be a challenge, as chronic kidney disease is also an immunocompromised state causing a lower seroconversion rate. The protective immune response generated is also expected to fade earlier. Enumerable psychosocial barriers exist regarding vaccine acceptance and a tender bond between health care providers and patients is essential for the smooth conduct of the vaccination program. The tolerability and safety profile of different available vaccines are reassuring in the general population but more data are needed in transplant communities. In addition, the efficacy data of COVID-19 vaccines are derived from the general population and preliminary reports in transplant patients have shown weakened immune response to vaccination. As of May 2021, Indian government advisories have approved three vaccines: COVIDSHIELD, COVAXIN, and Sputnik. Hence, research on vaccine efficacy with different vaccine constituents, dosing, and intervals is necessary for an effective protocol for vaccination in transplantation.
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Social media and organ donation - A narrative review
p. 139
Gopal Basu, Sanjeev Nair, Sibel Gokcay Bek, Prashant Dheerendra, Krishnam Raju Penmatsa, Karthikeyan Balasubramanian, Aakash Shingada, Arvind Conjeevaram
DOI
:10.4103/ijot.ijot_138_20
Increasing demand for organ transplantation which is often the lifesaving treatment for organ failure and a shortage of organs is a crisis prevalent in many countries. Proactive engagement of the society by improving awareness about organ donation is perceived to be the key to address the problem of organ shortage. In the current digital era, social media (SoMe) organ donation campaigns are one of the most practical and effective ways to disseminate information and promote collaboration among participants. Many governmental and nongovernmental organizations and social activists are utilizing popular SoMe platforms such as Facebook, Twitter, YouTube, and Instagram to promote organ donation awareness. Although such SoMe campaigns are impactful and open unique possibilities to address organ shortage, one should also be aware of the challenges of maintaining confidentiality, the potential for misuse, misinformation, and negative framing. In this narrative review, we review the use of SoMe to promote organ donation including its benefits, pitfalls, and attempt to list some recommendations.
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Pathobiology of Non-HLA immunity in renal transplantation
p. 147
Praveen Kumar Etta, Thatipamula Madhavi, Namrata Parikh
DOI
:10.4103/ijot.ijot_57_20
Conventionally, major histocompatibility complex (MHC)-encoded human leukocyte antigens (HLAs) of a donor are considered as the principal targets of the recipient's immune system in renal transplantation (RT), and the clinical significance of anti-HLA allo-antibodies (Abs) is well established. In contrast, the importance of non-HLA immunity in RT is being increasingly recognized. Majority of non-HLA immune targets are the non-MHC-encoded proteins on vascular endothelial cells and exist as cryptic autoantigens. The synergistic triad of tissue injury, anti-HLA, and non-HLA immunity is involved in many cases of graft rejection and loss. The exact mechanisms by which the non-HLA auto-Abs are produced and induce graft injury are still speculative and under research. Understanding them enables the development of novel diagnostic assays and therapeutic strategies and thereby improves long-term graft outcomes. In this review, we discuss the pathobiology and novel mechanisms of non-HLA immunity in RT.
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Immunosuppression in lung transplantation: Changing perspectives
p. 157
Unmil Shah, Vijil Rahulan, Pradeep Kumar, Prabhat Dutta, Sandeep Attawar
DOI
:10.4103/ijot.ijot_98_20
Lung transplantation is a definitive treatment option for select end-stage lung disease patients. Post lung transplantation, immunosuppression plays a significant role in a successful outcome. Rejection and infection are commonly encountered where immunosuppression plays an important role. Many immunosuppressive strategies have been designed and their protocols might vary from center to center. This review will focus on these perspectives as well as emerging perspectives during COVID times.
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CASE REPORTS
A directed deceased donation that never was - A case report
p. 166
Avnish Kumar Seth, Twinkle Singh
DOI
:10.4103/ijot.ijot_45_20
The family of a 48-year-old female with brain death requested for directed donation of a kidney to her brother. Failure to comply with the wishes of the family due to medical reasons resulted in the withdrawal of consent for the donation of all organs. The status of deceased directed donation is discussed and a checklist suggested for the same in India.
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Invasive fungal diseases in renal transplantation - Case series
p. 169
Kartik Ganesh, M Abi Abraham, Jithin S Kumar, Sunita Simon
DOI
:10.4103/ijot.ijot_28_20
We describe 6 cases of invasive fungal diseases in the post kidney transplant setting. These include 2 cases each of mucormycosis and Aspergillosis and 1 case each of pheohyphomycosis and histoplasmosis. Our case series includes the first described case of aspergillus sacroilitis post kidney transplant and also reviews the literature on various modalities of treatment of fungal infections, follow up, diagnostic modalities and appropriate drug choices.
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Progressive familial CD10 deficient ductopenic disorder; Hitherto an unnamed entity! - A case report
p. 176
Nalini Bansal, Mukul Rastogi, Vivek Vij
DOI
:10.4103/ijot.ijot_29_20
Inherited liver disorders are group of genetic diseases that cause early liver involvement many of them progressing to early cirrhosis. Of the familial cholestatic disorders most widely studied are progressive familial intrahepatic cholestatic disorders. These disorders are caused by defects in enzymes involved with the formation and excretion of bile constituents. They are, however, not associated with ductopenia. We herein report the first case of a familial cholestatic disorder in three female siblings resident of Lahore, Pakistan presenting as chronic cholestasis all progressing to cirrhosis before 10 years of age. The first two female siblings underwent liver transplants for chronic cholestasis. The third sibling underwent liver biopsy for the evaluation of cholestasis and later liver transplant for same. There are no other associated cardiac or skeletal anomalies in any of the sisters. The findings of biopsy and explant tissue were similar in all three sibling sisters. There are features of advanced fibrosis, significant ductopenia, bile ductular reaction at the porto-parenchymal interface, cholestasis, increased copper stores on rhodanine stain no loss of bile salt export pump, and multi-drug resistant 3 protein (MDR3), and the absence of CD10 from canaliculi. The findings raised differentials for progressive familial intrahepatic cholestasis (PFIC) type 3, Alagille syndrome, and variant of familial cholestatic disorder. PFIC 3 causes cholestasis, but the presence of MDR3 stain, ductopenia, and deficient CD10 are not seen in PFIC 3. Familial ductopenic disorders have been identified in the adult population called as idiopathic adulthood ductopenia and had autosomal dominant pattern of inheritance. The argument against Alagille syndrome is the absence of any other syndromic features of Alagille and autosomal recessive mode of inheritance. These findings led us to conclude if there is a need to redefine a new entity of progressive familial CD10 deficient ductopenic disorder. The findings though limited by genetic studies give way for further research on the subject.
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Case of renal transplant recipient with twin pregnancy - A case report
p. 181
Atul Kumar Srivastava, Md Rasheed, Indranil Ghosh, Sudhir Mansingh
DOI
:10.4103/ijot.ijot_51_20
Kidney transplant can restore fertility in young recipients. Preconception counseling should be done for each kidney transplant recipient (KTR) of childbearing age; however, multiple gestations can occur in these patients spontaneously and with assisted reproduction. Pregnancy in KTR can have impact on graft functioning and has obstetrical and fetal implications. We report a 28-year-old KTR with twin pregnancy following intrauterine insemination and challenges associated with it during the pregnancy.
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Bilateral superior parathyroid adenoma postkidney donation: A riddle, well, solved!! - A case report
p. 184
Avinash Rao Ullur, Shakuntala V Modi, Nitin M Nayak, Ramakrishnan Santanaraman, Dilip Rangarajan, Padmanabhan Subramanian
DOI
:10.4103/ijot.ijot_86_20
Kidney transplantation with living kidney donation is an optimal treatment modality for end stage kidney disease. Although the risks after kidney donation are few in number, the unrecognised complications due to suboptimal evaluation have been reported in the literature. We hereby report a case of a kidney donor, who was detected to have parathyroid adenoma on routine evaluation for metabolic bone parameters two years post kidney donation. Although she was treated timely, we learnt the importance of careful evaluation of the donor biochemistry prior to transplant.
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th
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