Advertisment

Indian Journal of Nephrology About us |  Subscription |  e-Alerts  | Feedback | Login   
  Print this page Email this page   Small font sizeDefault font sizeIncrease font size
 Home | Current Issue | Archives| Ahead of print | Search |Instructions |  Editorial Board  

Users Online:556

Official publication of the Indian Society of Nephrology

Ahead of print articles
ORIGINAL ARTICLE
Ahead of print publication  

Outcome of COVID-19 in kidney transplant patients from Eastern India: A single center study


1 Department of Nephrology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
2 Department of Community Medicine, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

Date of Submission09-Sep-2021
Date of Acceptance10-Mar-2022
Date of Web Publication16-Jul-2022

Correspondence Address:
Amresh Krishna,
Room No.: 14, Department of Nephrology, Old Administrative Block, Indira Gandhi Institute of Medical Sciences, Patna - 800 014, Bihar
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijn.ijn_385_21

  Abstract 


Introduction: COVID-19 in kidney transplant recipients (KTR) had been associated with high incidence of acute kidney injury and higher mortality. Management of these patients is still evolving. Methods: A retrospective observational study was done that included all KTR aged ≥18 years and ≤65 years who had COVID-19 diagnosis via RTPCR test between 1 June 2020 and 30 May 2021. Severity of COVID-19 was determined as per the guidelines given by Government of India. Acute kidney injury was defined according to KDIGO guideline. Data was collected and analyzed using SPSS version 16.0 (Chicago, SPSS Inc.). Results: Out of 34 patients, 29 were men. Median age of patients was 39.9 years and median time since transplantation was 34 months. Presenting symptoms were fever (100%), cough (79.4%), gastrointestinal symptoms (23.5%), and dysgeusia/anosmia (23.5%). COVID-19 was severe in 17.6%, moderately severe in 32.4%, and mild in 50% of patients. Time since transplantation, duration of symptoms, hospital stay and inflammatory markers like CRP, LDH, ferritin and d-dimer were significantly associated with disease severity (P < 0.05). Steroids were increased in 55%, antiproliferative agents stopped in 97%, and calcineurin inhibitors stopped in 26% of patients. 70.6% of the patients were managed in home isolation. Acute kidney injury occurred in 58.8% cases. 75% of the AKI patients recovered by 28 days after discharge. Conclusion: Our study showed that outcome of COVID-19 in kidney transplant patients was reasonably good.

Keywords: Acute kidney injury, COVID-19, kidney transplant recipients, outcome, severity



How to cite this URL:
Singh PP, Krishna A, Singh T, Patel PS, Kumar A, Kumar O. Outcome of COVID-19 in kidney transplant patients from Eastern India: A single center study. Indian J Nephrol [Epub ahead of print] [cited 2022 Aug 19]. Available from: https://www.indianjnephrol.org/preprintarticle.asp?id=351269


  Introduction Top


The novel corona virus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of Coronaviridae family. The disease started at Wuhan, China in December 2019 leading to the ongoing global pandemic.[1] The record spike, noted in COVID-19 since March 2021 in India, has crippled lives and overwhelmed available health infrastructure. The government imposed “strict lockdown” in most of the states again in April 2021. Till 31 August 2021, India had reported 32,810,845 cases of COVID-19 with 439,020 (1.34%) deaths and Bihar state had 725,708 cases with 9653 deaths (1.33%).[2] The virus usually involves the respiratory tract; in severe cases, renal dysfunction and multi-organ failure are also seen. Kidney transplant recipients (KTR) are at higher risk of infection.[3–7] Recent studies have shown higher incidence of acute kidney injury (AKI) and significantly higher morbidity and mortality from COVID-19 in KTR as compared to general population and cohorts with other risk factors.[4–9] Management of KTR with COVID-19 remains challenging. There is no clear consensus on how to modify immunosuppression. Although interventions like HCQS, steroids, convalescent plasma transfusion and other experimental drugs were used in general population, their role in transplant patients remains uncertain. Recent studies have shown no significant benefit of these interventions except steroids.[10],[11] In contrast to higher mortality shown in various studies in India and abroad,[4–9] one case series of nine patients from eastern India showed no mortality or significant sequelae.[12] With this background, we studied the outcome, clinical and laboratory parameters, and management of COVID-19 in KTRs in Bihar, a resource-constrained state[13] of eastern part of India.


  Methods Top


This is a retrospective observational study done at Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India. The study was approved by the institute ethics committee (letter no. 132/IEC/IGIMS/2021). All kidney transplant recipients aged more than 18 years and less than 65 years evaluated at IGIMS and tested positive on RT-PCR test for SARS-CoV-2 between 1 June 2020 and 30 May 2021 were included in the study. Severity of the COVID-19 was determined as per “CLINICAL MANAGEMENT PROTOCOL FOR COVID-19”, published by Ministry of Health and Family Welfare, Government of India.[14] AKI was defined as increase in serum creatinine ≥0.3 mg/dl within 24 hours or ≥1.5 times the baseline.[15]

Clinical data including age, sex, transplant vintage, immunosuppressive treatment, comorbidities, signs and symptoms, severity, and biochemical parameters including kidney function tests, liver function tests, and inflammatory markers were noted. Data were collected at the time of hospitalization, at the time of discharge, and at follow up done one month after discharge, from hospital records and electronic communications (e.g., telephone/SMS/WhatsApp®/emails).

Data was collected, compiled, processed, and analyzed using SPSS for Windows, version 16.0 (Chicago, SPSS Inc.). The categorical variables were expressed as number and percentage, and continuous variables were shown as mean, standard deviation, median and interquartile range (IQR), where appropriate. For comparing categorical variables, Chi-squared test or Fisher's exact test (when expected frequencies of cells were < 5) were used. Shapiro–Wilk test of normality was performed and data was found to be not normally distributed for many independent variables. As the assumptions of ANOVA were violated due to non-normality and outliers in the data, Kruskal–Wallis H test was performed. P value of <0.05 was considered significant.


  Results Top


We had 194 KTRs in our active follow up in 2020–2021. Out of 194 KTRs, 34 (17.5%) were detected COVID-positive by RT-PCR method over 12 months period from 1 June 2020 to 31 May 2021. 29 patients (85%) were men with a median age of 39.9 years. Baseline characteristics of the patients and transplantation are given in [Table 1]. All but one had received live kidney donation. 28 patients (82.4%) had received anti-thymocyte globulin (ATG) induction at the time of transplant and all were on triple immunosuppressive agents (ISA) including prednisolone, calcineurin inhibitors (CNI)/mTOR inhibitors, and mycophenolate mofetil (MMF). History of graft rejection was present in six patients (acute antibody mediated and acute cellular rejections in three each).
Table 1: Baseline characteristics of kidney transplant recipients with COVID-19

Click here to view


Presenting symptoms were fever (100%), cough (79.4%), shortness of breath (38.2%), gastrointestinal symptoms (23.5%), and dysgeusia and/or anosmia in 23.5% cases [Table 2]. None of the patients developed complications related to bleeding diathesis or hypercoagulation. Laboratory parameters according to severity of COVID-19 are presented in [Table 3]. COVID-19 was severe in six (17.6%), moderately severe in 11 (32.4%) and mild in 17 (50%) patients. In mild, moderate and severe cases, median oxygen saturation (SPO2) was 97%, 93%, and 84% respectively. Overall, 24 patients (70.6%) were managed in home isolation. Out of ten hospitalized patients, one patient each needed BiPAP and mechanical ventilation.
Table 2: Clinical parameters of kidney transplant recipients with COVID-19

Click here to view
Table 3: Laboratory parameters according to severity of COVID-19

Click here to view


Dose of prednisolone was not changed in 15 patients (44.1%) and increased in 12 (35.3%). Prednisolone was substituted with dexamethasone in 6 patients (17.6%) while with intravenous methyl prednisolone in 1 patient. Antiproliferative drugs were stopped in 33 patients and additionally CNI was stopped in 9 patients (26%) who had severe COVID-19 and/or had AKI. Three patients received remdesivir and one received favipiravir. AKI developed in 20 patients (58.8%). AKI occurred in 47%, 54.5% and 100% of mild, moderate and severe cases, respectively.

One patient who needed mechanical ventilation died and one patient who had chronic graft dysfunction and needed hemodialysis remained dialysis dependent even after 28 days since discharge.


  Discussion Top


India is among the most severely COVID-affected countries globally. COVID-19 overwhelmed the existing health system several weeks. Kidney transplant recipients are susceptible to COVID-19 infection with worst outcome as shown in few Indian studies[7],[16],[17] and also in various studies from different countries.[4],[5],[6],[8],[18] Although data regarding transplant recipients are now emerging in the form of case series and registries worldwide, the same from India are still limited. There is no published data on KTR with COVID-19 from eastern part of the India to the best of the authors' knowledge.

We present data on 34 kidney transplant patients affected with COVID-19. IGIMS is a low volume transplant center situated in a resource-constrained state. COVID positivity rate at our center is 17.5% which is much higher than that shown in various studies.[8],[9],[16],[17] 85% of kidney transplant recipients (KTRs) were male while 80% live donations came from women, reflecting prevalent gender bias in kidney transplant.[9] We had a relatively younger cohort of transplant recipients with a median age of 39.9 years.[8.9] Apart from immunosuppressive state, two most important risk factors for COVID-19 namely hypertension and diabetes were seen in approximately 80% and 25% patients, respectively. Disease severity varied from severe (17.6%), moderately severe (32.4%), to mild (50%) patients similar to that observed in Indian reports.[4],[16] The incidence of AKI (58%) was at par with other studies reporting incidence of AKI ranging from 42%–57%.[4],[7],[8],[9],[19] Out of 20 AKI patients, only seven (35%) had serum creatinine declined to their pre-COVID serum creatinine at the time of discharge, but follow up after 28 days showed recovery to pre-COVID serum creatinine in 15 (75%) patients.

Although there was no clear consensus on how to manage immunosuppression in these cases, learning from the past, we discontinued antimetabolites in all patients and decreased the dose of tacrolimus in almost half of the patients, including withdrawal of tacrolimus in one-fourth of cases with moderate-to-severe disease and in those with AKI. Prednisolone dose was increased in 35% cases while intravenous dexamethasone was used for short-term in 6 patients (17%) in accordance with RECOVERY trial recommendations.[11] 70% of kidney transplant recipients were managed at home with telemedicine support, 30% were admitted in the hospital and overall, 97% recovered from COVID-19.


  Conclusion Top


Kidney transplant recipients are at a high risk of contracting COVID-19 and acute kidney injury. Duration of symptoms and level of inflammatory markers were significantly associated with severity. Most of the patients were managed successfully at home and outcome of COVID-19 in kidney transplant patients was better in terms of higher recovery rate and lesser mortality.

Acknowledgment

We acknowledge our gratitude to all patients who consented for sharing their data and cooperated with us during the study period.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol 2020;92:479-90.  Back to cited text no. 1
    
2.
Available from: https://www.mohfw.gov.in/. [Last accessed on 2021 Sep 01].  Back to cited text no. 2
    
3.
Pal SP, Amit G, Vardhan H, Narayan P, Sharma RK. Pattern of infections in immediate post renal transplant period: A single centre experience. Indian J Transplant 2016;10:105-6.  Back to cited text no. 3
    
4.
Alberici F, Delbarba E, Manenti C, Econimo L, Valerio F, Pola A, et al. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney Int 2020;97:1083-8.  Back to cited text no. 4
    
5.
Akalin E, Azzi Y, Bartash R, Seethamraju H, Parides M, Hemmige V. Covid19 and kidney transplantation. N Engl J Med 2020. doi: 10.1056/NEJMc2011117.  Back to cited text no. 5
    
6.
Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M. Early experience with COVID-19 in kidney transplantation. Kidney Int. 2020;97:1074-5.  Back to cited text no. 6
    
7.
Kute VB, Bhalla AK, Guleria S, Ray DS, Bahadur MM, Shingare A, et al. Clinical profile and outcome of COVID-19 in 250 kidney transplant recipients: A multicenter cohort study from India. Transplantation 2021;105:851-60.  Back to cited text no. 7
    
8.
Toapanta N, Torres IB, Sellarés J, Chamoun B, Serón D, Moreso F. Kidney transplantation and COVID-19 renal and patient prognosis. Clin Kidney J 2021;14(Suppl 1):i21-9. doi: 10.1093/ckj/sfab030.  Back to cited text no. 8
    
9.
Mahalingasivam V, Craik A, Tomlinson LA, Ge L, Hou L, Wang Q, Yang K, et al. A systematic review of COVID-19 and kidney transplantation. Kidney Int Rep 2021;6:24-45.  Back to cited text no. 9
    
10.
WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al. Repurposed antiviral drugs for Covid-19-Interim WHO solidarity trial results. N Engl J Med 2021;384:497-511.  Back to cited text no. 10
    
11.
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704.  Back to cited text no. 11
    
12.
Krishna A, Singh PP, Vardhan H, Kumar O. Better outcome of coronavirus disease 2019 infection in kidney transplant recipients: A case series from eastern India. Saudi J Kidney Dis Transpl 2021;32:875-9.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Central Bureau of Health Intelligence (CBHI), MOHFW, GOI. National Health Profile 2019. 14th issue. Available from: www.cbhidghs.gov.in/showfile.php?lid=1147. [Last accessed on 2021 Jul 07].  Back to cited text no. 13
    
14.
Ministry of Health and Family Welfare. Government of India. CLINICAL MANAGEMENT PROTOCOL FOR COVID-19. Version 6. (Published on 24 May 2021). Available from: https://www.mohfw.gov.in/pdf/UpdatedDetailedClinical ManagementProtocolforCOVID19adultsdated24052021.pdf. [Last accessed on 2021 Jul 07].  Back to cited text no. 14
    
15.
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL et al. Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012;2:1-138. doi: 10.1038/kisup. 2012.1.  Back to cited text no. 15
    
16.
Bhandari G, Tiwari V, Gupta A, Bhargava V, Malik M, Gupta A, et al. COVID-19 infection in renal transplant patients: Early report from India. Indian J Nephrol 2021;31:271-5.  Back to cited text no. 16
  [Full text]  
17.
Kumaresan M, Babu M, Parthasarathy R, Matthew M, Kathir C, Rohit A, et al. Clinical profile of SARS-CoV-2 infection in kidney transplant patients-A single centre observational study. Indian J Transplant 2020;14:288-92.  Back to cited text no. 17
  [Full text]  
18.
Jager KJ, Kramer A, Chesnaye NC, Couchoud C, Sánchez-Álvarez JE, Garneata L, et al. Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe. Kidney Int 2020;98:1540-8.  Back to cited text no. 18
    
19.
Fisher M, Neugarten J, Bellin E, Yunes M, Stahl L, Johns TS, et al. AKI in hospitalized patients with and without COVID-19: A comparison study. J Am Soc Nephrol 2020;31:2145-57.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

 
Top
 
 
  Search
 
  

 
  In this article
   Abstract
  Introduction
  Methods
  Results
  Discussion
  Conclusion
   References
   Article Tables

 Article Access Statistics
    Viewed101    
    PDF Downloaded2    

Recommend this journal

Indian Journal of Nephrology
Published by Wolters Kluwer - Medknow
Online since 20th Sept '07