I-JAMM-(I): A survey providing an insight into the practices of isoagglutinin titration in ABO incompatible kidney and liver transplantation.

BACKGROUND AND OBJECTIVES: ABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration. METHODS: The survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire. RESULTS: Results were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants. CONCLUSION: With increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.

COVID-19: Clinical Course and Outcome of hospitalized Hemodialysis Patients: Single-center Experience.

BACKGROUND: There is a paucity of data regarding the consequences of coronavirus disease 2019 (COVID-19) infection in patients with maintenance hemodialysis (MHD). Our objective was to identify the clinical manifestations and prognostic factors and to assess the impact of treatment schemes on the outcomeMaterials and methods: Here we present retrospectively collected data from medical records of patients on MHD hospitalized with COVID-19 infection from 1st June to 30th November 2020Result: Around 69 patients were admitted with a median age of 51 years. About 81% had hypertension, 41% had diabetes, and 24% had body mass index (BMI) ≥ 23 kg/m2 . Of all who died, 73.33% had dialysis vintage of <12 months (p = 0.06). Common presenting symptoms were fatigue (67%), fever (58%), cough (42%), and dyspnea (35%). Milder, severe, and critical disease was found in 35, 45, and 20% of patients, respectively. About 54 patients were living 4 weeks after discharge. Around 15 patients died, that includes all who received invasive ventilatory support. Nonsurvivors were older and had lower oxygen saturation on admission, lower hemoglobin (Hb), and worst lactate dehydrogenase (LDH), interleukin (IL)-6, and D-dimer values than survivors, which were statistically significant. Use of remdesivir and anticoagulant improves chances of survival (p-value 0.035 and 0.034, respectively) Conclusion: About one-third of patients had mild disease. Those with critical disease displayed high mortality. Older age, male gender, short dialysis vintage, lower oxygen saturation on admission, anemia, leucocytosis, higher inflammatory markers [except C-reactive protein (CRP)], bilateral lung opacity, and requirement of the mechanical ventilator are poor prognostic factors. CRP, ferritin, and lymphopenia are not good prognostic markers unlike in the general population. These findings need to be verified in larger cohorts.

Ethical review of COVID-19 vaccination requirements for transplant center staff and patients.

Transplant centers seeking to increase coronavirus disease 2019 (COVID-19) vaccine coverage may consider requiring vaccination for healthcare workers or for candidates. The authors summarize current data to inform an ethical analysis of the harms, benefits, and individual and societal impact of mandatory vaccination, concluding that vaccine requirements for healthcare workers and transplant candidates are ethically justified by beneficence, net utility, and fiduciary duty to patients and public health. Implementation strategies should mitigate concerns about respect for autonomy and transparency for both groups. We clarify how the same arguments might be applied to related questions of caregiver vaccination, allocation of other healthcare resources, and mandates for non-COVID-19 vaccines. Finally, we call for effort to achieve global equity in vaccination as soon as possible.

Humoral and cellular response of COVID-19 vaccine among solid organ transplant recipients: A systematic review and meta-analysis.

BACKGROUND: We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response. METHODS: We did a systematic review and meta-analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID-19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547. RESULTS: Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40-0.48]) in overall and in control studies (log-Odds-ratio [OR]: -4.46 [-8.10 to -2.35]). The humoral response was highest in liver (ES: 0.67 [0.61-0.74]) followed by heart (ES: 0.45 [0.32-0.59]), kidney (ES: 0.40 [0.36-0.45]), kidney-pancreas (ES: 0.33 [0.13-0.53]), and lung (0.27 [0.17-0.37]). The meta-analysis for standard and booster dose (ES: 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92-0.96] vs. ES: 0.40 [0.39-0.41]; p-value < .01). The seroresponse with mRNA-12723 mRNA was highest 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) and Belatacept (OR: 1.89 [1.3-2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32-0.52]) in overall and control studies (OR: -3.12 [-0.4.12 to -2.13]). INTERPRETATION: Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required.

COVID-19 vaccination timing and kidney transplant waitlist management: An international perspective.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs worldwide. The aim of this study is to assess an international perspective on challenges faced by kidney transplant programs. METHODS: We administered an electronic survey instrument from January 3, 2021 to June 8, 2021 to staff at transplant programs outside the United States that comprised of 10 questions addressing the management of kidney transplant candidates with asymptomatic COVID-19 infection or unvaccinated who receive an organ offer. RESULTS: Respondents (n = 62) represented 19 countries in five continents. Overall, 90.3% of respondents encourage vaccination on the waiting list and prior to planned living donor transplant. Twelve percent of respondents reported that they have decided to inactivate unsensitized candidates (calculated panel reactive antibody, cPRA <80%) until they received the two doses of vaccination, and 7% report inactivating candidates who have received their first vaccine dose pending receipt of their second dose. The majority (88.5%) of international respondents declined organs for asymptomatic, nucleic acid testing (NAT)+ patients during admission without documented prior infection. However, 22.9% of international respondents proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. CONCLUSIONS: Practitioners in some countries are less willing to accept deceased donor organs for waitlist candidates with incomplete COVID-19 vaccination status and to wait longer before scheduling living donor transplant, compared to United States practices. Access to vaccinations and other resources may contribute to these differences. More research is needed to guide the optimal approach to vaccination before and after transplant.

Consequences of the first and second COVID-19 wave on kidney transplant recipients at a large Indian transplant centre.

BACKGROUND: There is a scarcity of data comparing the consequences of first and second COVID-19 waves on kidney transplant recipients (KTRs) in India. METHODS: We conducted a single-centre retrospective study of 259 KTRs with COVID-19 to compare first wave (March 15-December 31 2020, n = 157) and second wave (April 1-May 31 2021, n = 102). RESULTS: KTRs during second wave were younger (43 vs. 40 years; p-value .04) and also included paediatric patients (0 vs. 5.9%; p-value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p-value .007); COVID-19 positive patients had less frequent cough (32 vs. 13.8%; p-value .001), fever was less frequent (58 vs. 37%; p-value .001), and we observed fewer co-morbidities (11 vs. 20.6%; p-value .04). The percentages of neutrophils (77 vs. 83%; p-value .001) and serum ferritin (439 vs. 688; p-value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p-value .0001). Hydroxychloroquine (11 vs. 0%; p-value .0001) and tocilizumab (7 vs. 0%; p-value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p-value .0001) and remdesivir (47 vs. 65%; p-value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p-value .01) and ICU admissions (20 vs. 37.2%; p-value .002) were more frequent during second wave. The 28-day mortality rate (9.6 vs. 10%; p-value 1) was not different. CONCLUSIONS: There has been a different clinical spectrum of COVID-19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre.

Safety and Tolerability of Remdesivir in Patients with End-stage Renal Disease on Maintenance Hemodialysis.

Introduction: The use of remdesivir is not recommended in patients with end-stage renal disease (ESRD) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless potential advantage offset disadvantage due to limited safety data. Our objective was to assess the safety of remdesivir in patients with end-stage renal failure and evaluate the outcome of this vulnerable group. Methodology: We carried out a retrospective observational study in dialysis-dependent ESRD patients with SARS-CoV-2 infection who received a standard 5-day course of remdesivir (powder form) from June 2020 to December 2020. Oxygen requirement, hemogram, inflammatory markers, and liver function tests before and after remdesivir treatment were compared. Result: We found thirty-nine such patients with mean age of patients 58.79 ± 12.13 years. Diabetes mellitus, hypertension, and cardiac diseases were present in 58.97, 87.17, and 23.07% of patients, respectively. Mean oxygen saturation on admission was 85.41% (±7.73). There were no events of hepatotoxicity, altered behavior, or infusion reaction. There was statistically significant improvement in total leukocyte count, absolute lymphocyte counts, and C-reactive protein (p value <0.001, 0.01, and 0.02, respectively) post remdesivir treatment. A total of 60% of patients had improved oxygenation while 13% of patients had no change in oxygen requirement after completion of remdesivir course. Mortality in our study was 28.21%. We did not find any significant benefit of early remdesivir administration (3-6 days of illness) on mortality or days of hospitalization. Conclusion: The use of remdesivir in end-stage kidney disease is safe. Improvement in oxygenation was significant when baseline oxygen requirement was less. It requires prospective controlled trials with larger population to assess its impact on mortality. How to cite this article: Shah MK, Parikh M, Prajapati D, Kute VB, Bhende P, Prajapati A, et al. Safety and Tolerability of Remdesivir in Patients with End-stage Renal Disease on Maintenance Hemodialysis. Indian J Crit Care Med 2022;26(5):619-625.

Organ Donation after Circulatory Determination of Death in India: A Joint Position Paper.

Organ donation following circulatory determination of death (DCDD) has contributed significantly to the donor pool in several countries. In India, majority of deceased donations happen following brain death (BD). While existing legislation allows for DCDD, there have been only few reports of kidney transplantation following DCDD from India. This document, prepared by a multidisciplinary group of experts, reviews international best practices in DCDD and outlines the path for DCDD in India. Ethical, medical, legal, economic, procedural, and logistic challenges unique to India have been addressed. The practice of withdrawal of life-sustaining treatment (WLST) in India, laid down by the Supreme Court of India, is time-consuming, possible only in patients in a permanent vegetative state, and too cumbersome for day-to-day practice. In patients where continued medical care is futile, the procedure for WLST is described. In controlled DCDD (category-III), decision for WLST is independent of and delinked from the subsequent possibility of organ donation. Families that are inclined toward organ donation are explained the procedure including the timing and location of WLST, consent for antemortem measures, no-touch period, and the possibility of stand-down and return to the intensive care unit (ICU) without donation. In donation following neurologic determination of death (DNDD), if cardiac arrest occurs during the process of BD declaration, the protocol for DCDD category-IV has been described in detail. In DCDD category-V, organ donation may be possible following unsuccessful cardiopulmonary resuscitation of cardiac arrest in the ICU. An outline of organ-specific requisites for kidney, liver, heart, and lung transplantation following DCDD and techniques, such as normothermic regional perfusion (nRP) and ex vivo machine perfusion, has been provided. The outcomes of transplantation following DCDD are comparable to those following DBDD or living donor transplantation. Documents and checklists necessary for successful execution of DCDD in India are described. How to cite this article: Seth AK, Mohanka R, Navin S, Gokhale AGK, Sharma A, Kumar A, et al. Organ Donation after Circulatory Determination of Death in India: A Joint Position Paper. Indian J Crit Care Med 2022;26(4):421-438.

Successful management of dengue in renal transplant recipients: A retrospective cohort from a single center.

INTRODUCTION: The literature on dengue infection in renal transplant recipients has shown wide diversity in clinical presentation and outcome. The objective of this study was to report the clinical profile, short-term and long-term outcomes of dengue among renal transplant recipients. METHODS: A total of 59 post-transplant dengue suspected cases were admitted from July 2019 to April 2020 of which 31 had confirmed dengue infection. The clinical and laboratory profile of the confirmed dengue cases (n = 31) were compared with non-dengue cases (n = 28). RESULTS: Among the clinical and laboratory features retro-orbital pain, conjunctival redness, thrombocytopenia on admission, and absence of arthralgia were significantly associated with dengue compared to non-dengue cases. No mortality was observed in the dengue cases. Allograft dysfunction, acute rejection and graft losses were identified in 64.5% (n = 20), 6.4% (n = 2) and 6.4% (n = 2) dengue cases respectively. No rejection or graft losses were observed in 1-year follow-up. CONCLUSIONS: We report a differential clinical profile for dengue in transplant settings which will aid in the diagnosis. We also report successful management of dengue infection in renal transplant recipients with the majority having allograft dysfunction. A long-term follow-up of the cohort was uneventful.

Non-simultaneous kidney exchange cycles in resource-restricted countries without non-directed donation - a prospective single-center cohort study.

Recent reports suggest that bridge-donor reneging is rare (1.5%) in non-simultaneous kidney exchange chains. However, in developing countries, the non-directed donors who would be needed to initiate chains are unavailable, and furthermore, limited surgical space and resources restrain the feasibility of simultaneous kidney exchange cycles. Therefore, the aim of this study was to evaluate the bridge-donor reneging rate during non-simultaneous kidney exchange cycles (NSKEC) in a prospective single-center cohort study (n = 67). We describe the protocol used to prepare co-registered donor-recipient pairs for non-simultaneous surgeries, in an effort to minimize the reneging rate. In addition, in order to protect any recipients who might be left vulnerable by this arrangement, we proposed the use of standard criteria deceased-donor kidneys to rectify the injustice in the event of any bridge-donor reneging. We report 17 successful NSKEC resulting in 67 living-donor kidney transplants (LDKT) using 23 bridge-donors without donor renege and no intervening pairs became unavailable. We propose that NSKEC could increase LDKT, especially for difficult-to-match sensitized pairs (25 of our 67 pairs) in countries with limited transplantation resources. Our study confirms that NSKEC can be safely performed with careful patient-donor selection and non-anonymous kidney exchanges.

Long-term follow-up of SARS-CoV-2 recovered renal transplant recipients: A single-center experience from India.

INTRODUCTION: Follow-up studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in kidney transplant recipients (KTR) are scarcely reported. METHODS: We studied 142 hospitalized KTR for a median (interquartile range) follow-up of 9 (8-11) months who recovered from SARS-CoV-2 during May 2020 to Dec 2020. The outcomes were to assess persistent symptoms post-discharge; EuroQoL visual analogue score (EQ-VAS); EuroQoL 5-dimension score (E5-QD-5L) score and modified medical research dyspnea score (mMRC) at 1 month, 3-month, and beyond 6 months. Graft outcome was also analyzed. RESULTS: The age of the cohort was 43 (34-69) years and COVID-19 severity ranged from asymptomatic (4%), mild (50%), moderate (35%) to severe (12%). The most common persistent symptom was fatigue which significantly decreased in the follow-up (n = 45 [32.3] vs. 10 [7.4] vs. 4 [2.9]; p-value = 0.001) at 1-month, 3-month, and beyond 6 months respectively. Decrement in the mean (standard deviation) EQ-VAS score from baseline was also improved (28.6 [13] vs. 10.4 [12.5] vs. 7.5 [12.0]; p-value = 0.012). There was significant improvement in all EQ-5D-5L scores in follow-up. There was no deterioration in mMRC scores during the follow-up (n = 4, 3% vs. 7, 5% vs. 3, 2%; p-value = 0.86). Cases requiring oxygen had significantly poorer overall scores initially, but there was no difference at 6 months. All 10 graft losses had oxygen requirement and chronic graft dysfunction at baseline. CONCLUSION: Our initial assessment reports significant improvement in the quality of life in follow-up. The majority recovered from allograft dysfunction. Further research is warranted to study the full spectrum of follow-up.

Feasibility and safety of remdesivir in SARS-CoV2 infected renal transplant recipients: A retrospective cohort from a developing nation.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has drastically impacted the transplant communities. Remdesivir (RDV) has shown some promising results in coronavirus disease (COVID-19) albeit with low certainty. Data in kidney transplant recipients (KTR) are still lacking. METHODS: This was a retrospective cohort of 57 moderate to severe COVID-19 positive KTR in a single center who received RDV as a part of COVID-19 management. No dose adjustments were done. The outcomes were measured as acute kidney injury (AKI) recovery; liver function tests abnormalities; other side effects; graft loss and death. RESULTS: The median (inter-quartile range) age of presentation was 44 (31-51) years. The duration from onset of symptoms to RDV initiation was 6 (5-7) days. Thirty-two (56%) cases received RDV on the day of admission. Forty-six (81%) cases were on oxygen support upon initiation of RDV. Thirty-eight (66.6%) cases had acute kidney injury on admission. The median baseline, admission, and 28-day follow-up serum creatinine of the cohort were 1.59 (1.1-2.1), 2.13 (1.3-3.1), and 1.58 (1.05-2.1) mg/dl, respectively. A total of 8(14%) cases died in the study with 1 (1.7%) graft loss. All those cases that died were on oxygen therapy at the time of initiation of RDV. No liver function derangements or any other major adverse events with the drug were reported. CONCLUSION: RDV therapy is safe and clinically feasible in renal transplant recipients as seen in our cohort. Larger clinical registries and randomized clinical trials should be conducted to further explore the efficacy in transplant recipients.

Expanding donor pool by utilizing deceased donors with snake envenoming.

In India, the deceased kidney transplant program is still in its preliminary stage, and accepting deceased donors with snakebite is just a forward step to expand the donor pool. We report here the outcome of 8 successful renal transplantations from brain-dead donors who died from a neurotoxic snakebite. We accepted them as donors as they had no evidence of hemotoxic snakebite. 7 recipients did well. 1 died due to sepsis with a functioning graft. 1 required renal biopsy that showed acute tubular necrosis. 1 required re-exploration due to graft collection due to a surgical issue. Patient and graft survival in follow-up were similar to other matched deceased donors in our center. According to our experience, utilizing brain-dead donors who died from a neurotoxic snakebite is safe and may dramatically expand the donor pool especially in countries where death due to snakebite is high in numbers.

Hospitals may Become "Disease Hotspots" for COVID-19 amid Shortage of Personal Protective Equipment.

How to cite this article: Patel MP, Kute VB, Goswami J, Balwani MR. Hospitals may Become "Disease Hotspots" for COVID-19 amid Shortage of Personal Protective Equipment. Indian J Crit Care Med 2020;24(11):1145-1146.

Impact of single centre kidney paired donation transplantation to increase donor pool in India: a cohort study.

In a living donor kidney transplantation (LDKT) dominated transplant programme, kidney paired donation (KPD) may be a cost-effective and valid alternative strategy to increase LDKT in countries with limited resources where deceased donation kidney transplantation (DDKT) is in the initial stages. Here, we report our experience of 300 single-centre KPD transplantations to increase LDKT in India. Between January 2000 and July 2016, 3616 LDKT and 561 DDKT were performed at our transplantation centre, 300 (8.3%) using KPD. The reasons for joining KPD among transplanted patients were ABO incompatibility (n = 222), positive cross-match (n = 59) and better matching (n = 19). A total of 124 two-way (n = 248), 14 three-way (n = 42), one four-way (n = 4) and one six-way exchange (n = 6) yielded 300 KPD transplants. Death-censored graft and patient survival were 96% (n = 288) and 83.3% (n = 250), respectively. The mean serum creatinine was 1.3 mg/dl at a follow-up of 3 ± 3 years. We credit the success of our KPD programme to maintaining a registry of incompatible pairs, counselling on KPD, a high-volume LDKT programme and teamwork. KPD is legal, cost effective and rapidly growing for facilitating LDKT with incompatible donors. This study provides large-scale evidence for the expansion of single-centre LDKT via KPD when national programmes do not exist.

Invasive fungal infections in renal transplant patients: a single center study.

BACKGROUND: Timely diagnosis of invasive fungal infections (IFI) in renal transplant (RT) patients on immunosuppression is often difficult, jeopardizing their life and graft. We reported IFI and their causative fungal agents in post-RT patients. MATERIALS AND METHODS: This was a retrospective 6-year clinical study carried out from 2010 to 2015 on 1900 RT patients. Clinical data included patient-donor demographics, time to onset of infection, risk factors and graft function in terms of serum creatinine (SCr). To identify IFI, we examined bronchoalveolar lavage (BAL), blood, tissue, and wound swab samples by conventional mycological methods. RESULTS: IFI were diagnosed in 30 (1.56%) patients on triple immunosuppression, mainly males (n = 25) with mean age of 36.57 ± 11.9 years at 13.12 ± 18.35 months post-RT. Aspergillus species was identified in 11 BAL, one tissue, and one wound specimen each, 30.76% of these were fatal and 15.38% caused graft loss; Candida albicans was in nine BAL, four blood, two wound swab, and one tissue specimens, 25% of these were fatal and 25% had graft loss and one mucor in BAL which was fatal. Seven patients were diabetic, 10 had superadded cytomegalovirus infection, and 15 were anti-rejected. CONCLUSION: IFI are associated with increased morbidity and mortality in RT patients. Triple immunosuppression, broad spectrum antibiotics for ≥ two weeks, diabetes and superadded infection are added risks for these patients. Prevention, early diagnosis, and appropriate management are necessary to improve their prognosis.