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Infection Patterns and Survival Among Renal Transplant Recipients

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Background The outcome of kidney transplantation is determined by multiple factors and infections represent one of the major factors affecting graft and patient survival. Recent COVID-19 pandemic have adversely affected the transplant population. Very little data is available on post-transplant infections and patient survival from India. Materials and Methods In this retrospective observational study, data related to post-transplant infections from patients who had undergone renal transplantation between October 2014 and October 2021 were collected. Results A total of 255 infections episodes were observed in 118 patients. Bacterial infections were the most common (55%) followed by viral (35%), fungal (5%), mycobacterial (4%), and parasitic (1%). The most common bacterial and viral infections were urinary tract infections (70.5%) and COVID-19 (56%), respectively. BK virus and COVID-19 were associated with increased graft loss (p < 0.05). The majority of deaths due to infections were related to COVID-19 infection (71.42%). Kaplan-Meier survival analysis showed 1-, 3-, and 5-year patient survival of 98.23%, 96.36%, and 92.90% and graft survival of 98.14%, 95.97%, and 91.78, respectively. Conclusion Infections with their adverse impact remain a concern in kidney transplant patients. Comparable patient and graft survival to the Western data despite the high infection burden and the COVID-19 pandemic suggests that effective management can reduce the impact of infections on survival.

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Introduction Coronavirus disease 2019 (COVID-19) pandemic led to a sudden drop in renal transplant numbers across India in the initial months of 2020. Although the transplant numbers increased with easing of lockdown, the outcome of these transplants remains unknown. Methods This was a retrospective, observational, multi-center study done across 8 different transplant centers in India. All the transplants done from 30/01/2020 till 31/12/2020 were included. The primary outcomes studied were patient and death censored graft survival as well as incidence of COVID-19 infection and its outcomes. Results During the study period a total of 297 kidney transplants were done. After a median follow up of 265 days the patient and death censored graft survival was 95.3% and 97.6% respectively. Forty-one patients (13.8%) developed COVID-19 post-transplant. Majority (58.5%) were asymptomatic to mildly symptomatic and the case fatality ratio was 14.6%. On multivariable logistic regression analysis older age was associated with higher likelihood of COVID-19 infection (odds ratio 1.038; CI 1.002 to 1.077). Conclusions Patient and graft outcome of kidney transplants done during the COVID-19 pandemic in India was acceptable. The incidence of COVID-19 was 13.8% with a high case fatality ratio. This article is protected by copyright. All rights reserved
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Background: Pulmonary infection is a leading cause of morbidity and mortality in renal transplant recipients. In a prospective study we characterized their epidemiology in a tropical country with high infectious disease burden. Methods: Adult renal transplant recipients presenting with pulmonary infections from 2015-2017 were evaluated using a specific diagnostic algorithm. Results: 102 pulmonary infections occurred in 88 patients. 32.3% infections presented in the first year, 31.4% between 1-5 and 36.3% beyond 5 years after transplantation. Microbiological diagnosis was established in 69.6%, 102 microorganisms were identified. Bacterial infection(29.4%) was most common followed by tuberculosis(23.5%),fungal(20.6%), Pneumocystis jiroveci (10.8%), viral(8.8%) and nocardial(6.9%) infections. Tuberculosis and bacterial infections presented throughout the post-transplant period, while Pneumocystis(72.7%), cytomegalovirus(87.5%) and nocardia(85.7%) predominantly presented after >12 months. Fungal infections had a bimodal presentation, between 2-6 months(33.3%) and after 12 months(66.7%). In 16.7% cases, plain radiograph was normal and infection was diagnosed by a computed tomography imaging. Mortality due to pulmonary infections was 22.7%. On multivariate cox regression analysis, use of ATG(HR-2.39, 95% CI:1.20-4.78,p=0.013), fungal infection(HR-2.14,95% CI:1.19-3.84,p=0.011) and need for mechanical ventilation(9.68, 95% CI:1.34-69.82,p=0.024) were significant predictors of mortality in our patients. Conclusions: Community acquired and endemic pulmonary infections predominate with no specific timeline and opportunistic infections usually present late. Nocardiosis and MDR TB are emerging challenges. Keywords: Pulmonary infections; renal transplantation.
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Current short term kidney post‐transplant survival rates are excellent, but longer term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1‐year and 5‐year graft survival and half‐lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n=331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/‐13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000‐2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014‐2017 (1995‐1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995‐1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995‐1999 to an estimated 19.2 years for transplants in 2014‐2017. In conclusion, these data show continuous improvement in long term outcomes with more notable improvement among higher risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.
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Aim: To study the incidence, pattern of tuberculosis, Its risk factors, and prognosis in renal transplantation recipients in Indian population. Settings and design: This study retrospectively analyzed the patients who underwent renal transplantation at Ramaiah medical college Hospitals, India from 2004 to 2015. Methods and material: The study enrolled 244 patients. Diagnosis was based on radio0imaging, sputum smear, culture and polymerase chainreaction and histology. Statistical analysis used: A descriptive univariate analysis was performed to identify the individual risk factors. Results: The TB infection was present in 21/244 (8.6%) renal transplantation patients (mean age ± SD = 44.3 ± 12.9 years). Pulmonary tuberculosis was the commonest (57%) followed by extrapulmonary tuberculosis (43%). Type II diabetes mellitus (DM) (14.6%; p = 0.0169)was significant risk factor. Majority of the patients (n = 18, 10.7%) were on standard tripledrug immunosuppression. The median duration of anti0tubercular therapy was 14 months and crude mortality was 19%. Conclusions: High index of suspicion for tuberculosis is require d in renal transplant recipients owing to their immunocompromised status and atypical presentations. Higher age, DM and use of immunosuppressants increase the risk for post0renal transplantation tuberculosis. Interactions between anti0tubercular drugs and immunosuppressants need to be considered in these patients.
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Introduction: Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipient (RTR). Immunosuppressive drugs are one of the most important risk factor for post-transplant tuberculosis (PTTB). A paucity of data exists about the impact of the type of calcineurin inhibitor on PTTB. Methods: In this retrospective study, all adult patients on calcineurin inhibitor-based immunosuppression were included. Patients receiving TB chemoprophylaxis were excluded. Diabetes, duration of dialysis, hepatitis B and C, past treated TB, induction therapy, type of antimetabolite, acute rejection, new onset of diabetes after renal transplantation (RT) (NODAT) and cytomegalovirus (CMV) were analyzed in tacrolimus (Tac) and cyclosporine (CsA) groups. Primary outcome was incidence of TB and secondary outcomes were timeline of development of TB after RT and pattern of TB in the 2 groups. Results: Of the 1664 patients included, 582 patients received CsA-based immunosuppression while 1082 received Tac-based immunosuppression. Duration of dialysis, positive tuberculin skin test, use of induction, mycophenolate mofetil use, CMV infection, and NODAT were significantly more and, hepatitis B infection, past treated TB and acute rejection episodes were significantly less in the Tac group. At the end of follow-up, incidence of TB in the Tac group was significantly less that CsA group (6.1% vs. 19.9%, P<0.001). Mean time for development of TB after RT was similar in both the groups and nodal and disseminated TB were more common in the Tac group. Conclusion: In conclusion, our study shows that use of Tac as compared to CsA significantly decreases incidence of PTTB. Time of infection since transplant was similar in both the groups. However, nodal and disseminated TB were more common in the Tac group. This article is protected by copyright. All rights reserved.
Article
Infections after transplantation account for half the deaths that occur in this group of patients in India. The spectrum of infections, their chronological occurrence, and the risk factors are different from that of developed regions. The diagnostic and therapeutic protocols are adapted to the different medical and socioeconomic environment. Tuberculosis affects 10% to 15% of renal allograft recipients; the risk is twofold and fourfold greater in those with hyperglycemia and chronic hepatitis, respectively. Pretransplantation tuberculosis is predominantly located in the lymph nodes, whereas after transplantation, the disease is often disseminated and manifested earlier due to cyclosporine therapy. Gastric juice smears and cultures for Mycobacterium tuberculosis were found to be useful tests in this group. Primary drug resistance to this organism was a problem. Isoniazid prophylaxis offered some protection from tuberculosis but was limited in the high-risk population with hepatitis. The prevalence of deep mycoses was 3.8% to 6.1% and was associated with 70% mortality. Pneumocystis carinii pneumonia emerged after 1991. Nocardiosis occurred earlier in patients who received cyclosporine and was manifested frequently, along with tuberculosis and other infections. Chronic liver disease affected 30% of patients and caused 8% of deaths. It was an important comorbid factor in patients with serious infections. Hepatitis B virus was seen in 40% of patients and hepatitis C virus in 15%. Cytomegalovirus infection was found in 20% of patients. Plasmodium falciparum infected 22.5% of renal transplant patients in western India and produced acute renal failure in 60%. Most malignancies encountered in India have had a presumed viral origin. The pattern of infections changes as immunosuppressive protocols vary and as the use of hepatitis B vaccine, hepatitis C virus screening, erythropoetin, and chemoprophylaxis becomes the standard practice in India.
Article
Introduction : The major bane of renal transplantation recipients is infection. One quarter of all renal transplant recipients in the tropical countries develop a serious infection at some point in the post transplant period, that causes allograft dysfunction. Death was always a hazard. Many of these infections are endemic to the region. A multitude of factors including unhygienic conditions, tropical climate, late presentation, lack of knowledge about the spectrum of organisms in these areas, diagnostic techniques and lifesaving anti microbial agents available only at a premium had contributed to dismal outcome. Therefore we studied the pattern of infections in renal allograft recipients, their incidence, the time of onset and the influence on allograft function Materials and methods : A retrospective study of infections in renal transplant recipients from 1989 to December 2003 was undertaken. Results : An analysis of data of169 renal allograft recipients was done. The mean age of the renal allograft recipients was 34.1+ 11.4 years (range: 10-60 years). 136 patients were males. CMV, Tuberculosis and fungal infections were observed at a prevalence of 21.8%, 10.6% and 23.0% respectively. Fungal infections carried a high mortality of 54%. The protean manifestations of the opportunistic infections and non-availability of sensitive diagnostic tests in most centers in the underdeveloped countries often delay the diagnosis. Hence a time table of infections has been devised to guide the Nephrologist in the optimum utilization of the resources. Urinary tract infections and line infections are most common in the first month after renal transplantation and Cytomegalovirus is most common between four weeks to 3 months after renal transplantation.Tuberculosis may be reactivated commonly between three months to one year post transplant. Pnuemocystis carinii & Aspergillus are life threatening hazards that occur after one year. No difference of infection prevalence has been found between patients who received either OKT3 or IL-2 receptor blockers. Diabetes mellitus and post-transplant diabetes mellitus have not predisposed to infection in our study. Conclusion : This study has brought to light the fact that infections can be an important differential diagnosis in the event of allograft dysfunction, due to their widespread distribution through out the post transplantation phase. The infections appear to follow a pattern studying which may help in diagnosing them quickly. The new chronological order of appearance of infections in renal allograft recipients presented in this study is relevant to present times and differs from previous two published ones-one Indian and another western.
Article
We studied the incidence and the risk factors predisposing to post transplantation urinary tract infection (UTI) and the association with use of different immunosuppressive regimens. We performed a retrospective analysis of 152 recipients of renal transplantation over a period of two years. Seventy one (46.71%) patients had culture positive UTI, Escherichia coli (45.1%) being the commonest. Thirty four (22.39%) patients had acute rejection and 14.4% of those had suffered UTI in the early post transplant period. Immunosuppression included induction with various antibodies and maintenance on antirejection medications. Trimethoprim-sulphamethoxazole was given as prophylaxis throughout the period. The UTI was treated according to microbiological sensitivity. 2.8% died due to urosepsis. In our retrospective analysis renal transplant recipients under the age of 45, female gender and diabetics suffered more UTI. Combination therapy with micro-emulsion form of cyclosporine A, prednisolone and azathioprine developed more UTI (P= 0.0418).
Article
Long-term survival in renal transplant recipients with graft function. Death with graft function (DWGF) is a common cause of graft loss. The risks and determinants of DWGF have not been studied in a recent cohort of renal transplant recipients. We performed a population-based survival analysis of U.S. patients with end-stage renal disease (ESRD) transplanted between 1988 and 1997. Registry data were used to evaluate long-term patient survival and cause-specific risks of DWGF in 86,502 adult (>/=18 years) renal transplant recipients. Out of 18,482 deaths, 38% (N = 7040) were deaths with graft function. This accounts for 42. 5% of all graft loss. Patient survival with graft function was 97, 91, and 86% at 1, 5, and 10 years, respectively. The risk of DWGF decreased by 67% (RR = 0.33, P < 0.001) between 1988 and 1997. The adjusted rate of DWGF was 4.6, 0.8, 2.2, and 1.4 deaths per 1000 person-years for cardiovascular disease, stroke, infections, and malignancy, respectively. The suicide rate was 15.7 versus 9.0 deaths per 100,000 person-years in the general population (P < 0. 001). In multivariate analysis, the following factors were independently and significantly predictive of DWGF: white recipient, age at transplantation, ESRD caused by hypertension or diabetes mellitus, length of pretransplant dialysis, delayed graft function, acute rejection, panel reactive antibody> 30%, African American donor race, age> 45 years, and donor death caused by cerebrovascular disease. Patients with graft function have a high long-term survival. Although DWGF is a major cause of graft loss, the risk has declined substantially since 1990. Cardiovascular disease was the predominant reported cause of DWGF. Other causes vary by post-transplant time period. Attention to atherosclerotic risk factors may be the most important challenge to further improve the longevity of patients with successful renal transplants.
Article
Systemic mycoses have a high impact on tropical renal-transplant recipients. Data from 1,476 primary renal-transplant recipients was prospectively recorded from 1986 to 2000 at a single center. Cumulative incidence of systemic mycoses, its time of occurrence, risk factors, outcome, and postmortem findings in 30 patients with systemic mycoses were analyzed. A total of 110 episodes of systemic mycoses occurred in 98 patients. The fungal genera Aspergillus, Cryptococcus, and Candida constituted 61% of pathogens, 45% localizing to the lungs. Cytomegalovirus (CMV) disease caused a 5-fold and chronic liver disease a 2-fold increase in systemic mycoses. Tuberculosis (TB) with or without nocardiosis was a significant coinfection. Cyclosporine (CsA) was associated with nearly a 4-fold risk of systemic mycoses less than 6 months from the time of transplantation as compared with prednisolone+azathioprine (PRED+AZA) therapy. Overall, the probability of survival with systemic mycoses was 73.4%, 60.8%, 39.5%, and 25.6% and was 92.5%, 87.5%, 80.0%, and 75.5% without systemic mycoses at 1, 2, 5, and 10 years, respectively (P<0.0001). An extended Cox model with time-independent and dependent covariates showed greater than 15 times the risk of death among those who develop systemic mycoses. Similarly, Posttransplantation (postTX) TB+/-Nocardiosis, preTX TB, CMV disease, diabetes mellitus, PTDM, chronic liver disease (>40 months), and Pred+AZA immunosuppression (>2 years) had 3.5, 1.5, 2.9, 1.9, 1.4, 1.6, 2.3 times the risk for death, respectively, as compared with those who did not have those risk factors. There is a recent predominance of Aspergillus among the transplant recipients. The risk factors for systemic mycoses are CMV disease, chronic liver disease, and hyperglycemia, and TB is an important coinfection. Systemic mycoses increased in the early postTX period with CsA. The risk factors for death are systemic mycoses, CMV disease, chronic liver disease (>40 months), diabetes mellitus, and Pred+AZA immunosuppression (>2 years). Overall, the probability of survival with systemic mycoses was poor; however, survival has recently improved.
Article
Risk factors for Nocardia infection in organ transplant recipients have not been formally assessed in the current era of transplantation. We performed a matched case-control study (1:2 ratio) between January 1995 and December 2005. Control subjects were matched for transplant type and timing. Univariate matched odds ratios were determined and conditional logistic regression was performed to identify independent risk factors. Clinical and microbiological characteristics of all case patients were reviewed. Among 5126 organ transplant recipients, 35 (0.6%) were identified as having cases of Nocardia infection. The highest frequency was among recipients of lung transplants (18 [3.5%] of 521 patients), followed by recipients of heart (10 [2.5%] of 392), intestinal (2 [1.3%] of 155), kidney (3 [0.2%] of 1717), and liver (2 [0.1%] of 1840) transplants. In a comparison of case patients with 70 matched control subjects, receipt of high-dose steroids (odds ratio, 27; 95% confidence interval, 3.2-235; P=.003) and cytomegalovirus disease (odds ratio, 6.9; 95% confidence interval, 1.02-46; P=.047) in the preceding 6 months and a high median calcineurin inhibitor level in the preceding 30 days (odds ratio, 5.8; 95% confidence interval, 1.5-22; P=.012) were found to be independent risk factors for Nocardia infection. The majority of case patients (27 [77%] of 35) had pulmonary disease only. Seven transplant recipients (20%) had disseminated disease. Nocardia nova was the most common species (found in 17 [49%] of the patients), followed by Nocardia farcinica (9 [28%]), Nocardia asteroides (8 [23%]), and Nocardia brasiliensis (1 [3%]). Of the 35 case patients, 24 (69%) were receiving trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis. Thirty-one case patients (89%) experienced cure of their Nocardia infection. Receipt of high-dose steroids, history of cytomegalovirus disease, and high levels of calcineurin inhibitors are independent risk factors for Nocardia infection in organ transplant recipients. Our study provides insights into the epidemiology of Nocardia infection in the current era, a period in which immunosuppressive and prophylactic regimens have greatly evolved.
Tuberculosis in renal transplant recipients: Our decade long experience with an opportunistic invader
  • M Eswarappa
  • Gayathri Devi
  • H J John
  • M M Chennabasappa
  • G K Siddaiah
Eswarappa M, Gayathri Devi H J, John MM, Chennabasappa GK, Siddaiah GM. Tuberculosis in renal transplant recipients: Our decade long experience with an opportunistic invader. Indian J Tuberc 2020;67:73-8.