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.

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.

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.

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.

Attitude and awareness towards organ donation in western India.

BACKGROUND: To determine the knowledge, attitudes and practices regarding organ donation in western India. METHODS: Convenience sampling was used to generate a sample of 250; 200 interviews were successfully completed and used for analysis. Data collection was carried out via face to face interviews based on a pre-tested questionnaire in selected public areas of Ahmedabad, Gujarat state of India. Data entry was made in excel software in codes and analysis was done by SPSS software. RESULTS: About 86% of participants were aware of the term organ donation but knowledge about its various aspects was low. About 48% aware people heard about organ donation through medical fraternity, whereas only about 21% became aware through mass media. About 59% of aware people believed there is a potential danger of donated organs being misused, abused or misappropriated. About 47% of aware people said they would consider donating organs, while only 16% said they would definitely donate irrespective of circumstances. Around 97.67% participants said they would prefer to donate to nonsmokers. About 74.41% participants were unaware about any legislation regarding organ donation. About 77% participants showed their will to donate to mentally sound persons, and 42.04% participants showed their will to donate even physically challenged people. Around 78 participants felt that they would donate organs to persons irrespective of their religion. About 81% of aware people were of the opinion that consent for organ donation after death should be given by family members. None of the interviewed participants had a donor card. CONCLUSION: Better knowledge and awareness will help in promoting organ donation. Effective campaign needs to be driven to educate people with relevant information with the involvement of media, doctors and religious scholars.

Increasing access to renal transplantation in India through our single-center kidney paired donation program: a model for the developing world to prevent commercial transplantation.

Because access to transplantation with HLA-desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end-stage renal disease (ESRD) patient in India. We present a government and institutional ethical review board approved study of 56 ESRD patients [25 two-way and 2 three-way pairs] who consented to participate in KPD transplantation at our center in 2013, performed to avoid blood group incompatibility (n = 52) or positive cross-match (n = 4). All patients had anatomic, functional, and immunologically comparable donors. The waiting time in KPD was short as compared to deceased donor transplantation. Laparoscopic donor nephrectomy was performed in 54 donors. Donor relationships were spousal (n = 40), parental (n = 13), others (n = 3), with median HLA match of 1. Graft survival was 97.5%. Three patients died with functioning graft. 16% had biopsy-proven acute rejection. Mean serum creatinine was 1.2 mg/dl at 0.73 ± 0.32 months follow-up. KPD is a viable, legal, and rapidly growing modality for facilitating LDRT for patients who are incompatible with their healthy, willing living donor. To our knowledge, this is the largest single-center report from India.

Mesenchymal stem cells and transplant tolerance.

Different strategies are being tried to induce transplant tolerance in clinical settings; however, none of them are both safe and effective. Mesenchymal stem cells have been found to be potent immunomodulators and immunosuppressants. We discuss in this review different sources of mesenchymal stem cells and the potent role of adipose tissue-derived mesenchymal stem cells in induction of transplant tolerance including when to use them and how to use them for achieving the Utopian dream of transplant tolerance.

Increasing access to kidney transplantation in countries with limited resources: the Indian experience with kidney paired donation.

According to the Indian chronic kidney disease registry, in 2010 only 2% of end stage kidney disease patients were managed with kidney transplantation, 37% were managed with dialysis and 61% were treated conservatively without renal replacement therapy. In countries like India, where a well-organized deceased donor kidney transplantation program is not available, living donor kidney transplantation is the major source of organs for kidney transplantation. The most common reason to decline a donor for directed living donation is ABO incompatibility, which eliminates up to one third of the potential living donor pool. Because access to transplantation with human leukocyte antigen (HLA)-desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end stage kidney disease patients. KPD is a rapidly growing and cost-effective living donor kidney transplantation strategy for patients who are incompatible with their healthy, willing living donor. In principle, KPD is feasible for any centre that performs living donor kidney transplantation. In transplant centres with a large living donor kidney transplantation program KPD does not require extra infrastructure, decreases waiting time, avoids transplant tourism and prevents commercial trafficking. Although KPD is still underutilized in India, it has been performed more frequently in recent times. To substantially increase donor pool and transplant rates, transplant centres should work together towards a national KPD program and frame a uniform acceptable allocation policy.

Outcome of renal transplantation from older living donors compared to younger living donor in developing country.

OBJECTIVES: To evaluate whether the outcomes of renal grafts from living related donors older than 60 years are acceptable, in terms of renal function and patient/graft survival. MATERIAL AND METHODS: One hundred and forty-seven patients who received kidneys from donor age ≥60 years constituted the study group (group 1). The control group (group 2) consisted of 1310 patients who received renal transplants from donor age <60 years. Outcome measures included graft, patient survival, acute rejection rate and serum creatinine (SCr) in patients/donors. Graft and patient survivals were compared using the Kaplan-Meier method. RESULTS: The mean age of donors was 62.7 ± 3.39 years in group 1 and 43.45 ± 9.65 years in group 2. Patient survival at 1, 3 and 5 years was 95.7%, 89.4% and 82.6% in group 1 and 93.8%, 89.1% and 83.1% in group 2 (p = 0.785), respectively. Death-censored graft survival at 1, 3 and 5 years was 98.5%, 94.8% and 94.8% in group 1 and 96.1%, 92.9% and 89% in group 2 (p = 0.166), respectively. Biopsy-proven acute rejections were 21% and 16.8% (p = 0.206) and chronic rejections 5% and 3.4% in group 1 and 2, respectively (p = 0.542). Recipient SCr (mg/dL) was 1.8 ± 0.31 in group 1 and 1.58 ± 0.37 in group 2. The donor SCr levels at the last follow-up were 1 mg/dL and 0.9 mg/dL in group 1 and 2, respectively. CONCLUSIONS: Donor age did not affect patient and graft survival in the 5-year follow-up in our study. Age alone seems not to be an exclusion criterion to living kidney donation.

Co-infusion of donor adipose tissue-derived mesenchymal and hematopoietic stem cells helps safe minimization of immunosuppression in renal transplantation - single center experience.

BACKGROUND: Stem cell therapy (SCT) is used for immunosuppression minimization in renal transplantation (RT). We carried out a prospective study to evaluate the benefits of co-infusion of donor adipose-derived mesenchymal stem cells (AD-MSC) + hematopoietic stem cells (HSC) in living donor RT (LDRT) under non-myeloablative conditioning. METHODS: In a demographically balanced three-armed LDRT trial with 95 patients in each arm, group-1 received portal co-infusion of AD-MSC + HSC, group-2 received HSC and group-3 received no SCT. Lymphoid irradiation and anti-thyroglobulin were used for conditioning. RESULTS: SCT was safe. At 1 and 5 years post-transplant, patient survival was 100% and 94.7% in group-1, 100% and 95.7% in group-2, and 94.7% and 84% in group-3, death-censored graft survival was 100% and 94.6% in group-1, 100% and 91.3% in group-2, and 98.9% and 94.4% in group-3 with mean serum creatinine (mg/dL) of 1.38 and 1.39 in group-1, 1.48 and 1.51 in group-2, and 1.29 and 1.42 and in group-3. Rejection episodes and immunosuppression requirement were lesser in SCT groups versus controls with best results noted in group-1. CONCLUSION: Coinfusion of donor AD-MSC +HSC in portal circulation pre-transplant under non-myeloablative conditioning is safe and effective for immunosuppression minimization in LDRT.

Outcome of renal transplantation from deceased donors: experience from developing country.

BACKGROUND: In India, there are a large number of end-stage renal disease (ESRD) patients waiting for renal transplantation (RT). Organ retrieval from brain dead deceased donor (DD) is getting increased attention as the waiting list for organ recipients far exceeds the organ donor pool. In our country, despite a large population, the number of brain dead donors undergoing organ donation is very less. DDRT is the possible solution to bridge the disparity between organ supply and demand. In India, the potential for DDRT is huge due to the high number of fatal road traffic accidents and this pool is yet to be tapped. PATIENTS AND METHODS: We report DDRT outcome in 294 patients (age: 36.5 ± 14.1 years; male:female, 200:94) between 2005 and 2012. All patients received single-dose rabbit-anti-thymocyte globulin for induction and steroids, calcineurin inhibitor, and mycophenolate mofetil/azathioprine for maintenance immunosuppression. RESULTS: Our retrospective study in 294 DDRT shows a fairly successful outcome. Over a mean follow-up of 3.93 years, patient and graft survival rates were 81.7% and 92.6%, respectively, with a median serum creatinine of 1.5 mg/dL. 20.7% had biopsy-proven acute rejection. CONCLUSION: Given the widespread organ shortage, DDRT has a potential to expand the donor pool and shorten the waiting list for RT, encouraging the use of this approach even in low-income countries. Aggressive donor management, increasing public awareness about the concept of organ donation, good communication between clinician and the family members, and a well-trained team of transplant coordinators can help in improving the number of organ donations.