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   Table of Contents - Current issue
July-September 2021
Volume 15 | Issue 3
Page Nos. 189-285

Online since Thursday, September 30, 2021

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Clinical characteristics and outcome of novel coronavirus disease in kidney transplant recipients: A single-center prospective observational study Highly accessed article p. 189
Venkatesh Arumugam, Bhagavatula V. R. H. Sastry, Dolphin J Solomon, Natarajan Gopalakrishnan, Badri Srinivasan Kannan, P Shankar, N Sheik Sulthan Alavudeen, Shivakumar Dakshinamoorthy, Malathy Natarajan
Background: Organ transplant recipients are at increased risk of infections which may result in acute graft dysfunction and death. Coronavirus disease (COVID-19) is the ongoing global infectious challenge and little is known about the impact of this novel virus in kidney transplant recipients. We here describe the clinical presentations, laboratory profile, and outcomes of 42 such patients, from a large tertiary care center in south India. Materials and Methods: This prospective, observational study included all renal transplant recipients with confirmed COVID-19 by reverse transcription polymerase chain reaction from the start of the outbreak till August, 2020. Clinical features at presentation, laboratory and radiological data, and outcomes were analyzed. Results: Forty-two patients were included in the analysis. As many as, 86.7% patients of our cohort had symptoms at presentation, with the most common symptoms being fever (52.5%), breathlessness (50%), and cough (40.5%). Significant need for respiratory support was noted in individuals with longer duration posttransplant (P < 0.03). Acute worsening of allograft function was observed in 22 (52.4%) patients. Fourteen (65%) of them had acute on chronic graft dysfunction and acute graft dysfunction was noted in 8 (35%) patients. Six patients (14.5%) died due to the disease and none of the parameters were found to be an independent predictor of mortality in regression analytic models including acute graft dysfunction (P = 0.49) or acute on chronic graft dysfunction (P = 0.07). There was no correlation between disease severity and baseline immunosuppressive agents whether tacrolimus or cyclosporine (P = 0.57) and mycophenolate mofetil or azathioprine (P = 0.91). Conclusions: Our largest cohort of patients from India showed higher incidence of acute graft dysfunction and significant mortality in patients with COVID-19.
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Changes in bone mineral density in patients undergoing kidney transplantation p. 199
Manjunath P Ramakrishna, Chankramath S Arun, Sandeep Sreedharan, Praveen V Pavithran, Nisha Bhavani, Renjitha Bhaskaran, Harish Kumar
Background and Aims: Bone health in chronic kidney disease (CKD) and its changes after kidney transplantation has been a subject of considerable interest. Kidney transplantation could potentially impact this process positively by reversing hyperparathyroidism, but immunosuppression including steroids could be deleterious to bone health. We studied the baseline and posttransplant bone mineral density (BMD) and factors affecting the changes in BMD after transplantation. Methods: Patients who were included in the study underwent biochemical tests and dual-energy absorptiometry for BMD. These tests were performed at baseline and 8 months after transplantation. Results: The mean BMD in lumbar spine was 1.09 ± 0.15 g/cm2 at baseline and 1.06 ± 0.15 g/cm2 posttransplantation (P = 0.002). The mean BMD at left forearm was 0.88 ± 0.10 g/cm2 at baseline and 0.89 ± 0.10 g/cm2 after transplantation (P = 0.013). The mean BMD at femur was 0.91 ± 0.16 g/cm2 and 0.89 ± 0.10 g/cm2 (P = 0.77) after transplantation. At baseline, intact parathyroid hormone (iPTH) had a significant negative correlation with femoral BMD (r = 0.44, P = 0.02) and 25-hydroxy Vitamin D (25(OH) Vit-D) had a positive correlation with forearm BMD (r = 0.50, P = 0.004). Eight months after transplantation, 25(OH) Vit-D levels showed a positive correlation with lumbar spine BMD (r = 0.36, P = 0.04). Cumulative steroid dose negatively correlated with spine BMD (r = −0.43, P = 0.01) posttransplantation. Conclusions: In this study, the baseline BMD was well preserved. Higher iPTH was associated with lower femoral BMD. Low 25(OH) Vit-D was associated with reduced forearm BMD. There was worsening of spinal BMD and improvement in forearm BMD 8 months after transplantation. No significant change in femoral BMD was noted. Cumulative steroid dose had a significant negative impact on BMD at spine. There were no fractures noted during the study, but two patients had avascular necrosis of the femur.
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Our renal transplant protocols during COVID-19 times – A prospective study from high-volume tertiary center of North India p. 205
Nripesh Sadasukhi, Ketul Patel, TC Sadasukhi, Manish Gupta, HL Gupta, Ashish Sharma, Sandeep Malik
Introduction: There is a strong temporal association between the increase in coronavirus disease-2019 (COVID-19) infections and a striking reduction in overall solid-organ transplantation procedure. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health-care systems in the backdrop of a virulent pandemic. Our current communication shares a protocol for donor and transplant recipient selection during the COVID-19 pandemic to continue lifesaving kidney transplantation. This protocol was created utilizing the guidelines of various organizations and from the clinical experience of the authors and will continue to evolve as more is understood about severe acute respiratory syndrome coronavirus 2 and how it affects organ donors and transplant recipients. Objectives: In this study, we aimed to review the published literature and compare it with our kidney transplantation is done in 115 patients in our hospital from July 2020 to February 2021 in the time of COVID-19 and what protocols we follow before transplant to reduce the risk of COVID-19 infection. This article also contains currently available immunosuppressive strategies. Methods: A prospective study was done in Mahatma Gandhi Hospital Jaipur for the transplant done from July 2020 to February 2021. A total of 115 patients from 20th July to 28th February were considered for the study. Results: All 115 patients who were COVID negative on reverse transcriptase–polymerase chain reaction assay and high-resolution computed tomography were considered for the transplant. COVID status on discharge for all 115 recipients was negative. During workup, two donors were found COVID-19 positive and were shifted to COVID center for treatment and their transplant postpone. Out of 115 renal transplant patients, only 1 patient became COVID-19 positive after 5 days of operation. Conclusions: Every transplant center should put its local policy about transplantation depending on the state of the epidemic in the country. Nowadays, transplantation programs should be limited to urgent cases. We suggest lowering the threshold for diagnosis of COVID-19 among renal transplant recipients.
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Correlation of three-dimensional computerized tomographic renal parenchymal volumetry with DTPA split renal function in prospective donors - A retrospective study p. 211
Pavankumar G Kale, G. P. Venkat Choudary, P Sandeep, Amancharla Y Lakshmi, V Siva Kumar, Ranadheer Mantri
Introduction: Split renal function (SRF) in prospective renal donors is traditionally measured by means of scintigraphy. Recent studies have reported the utility of three-dimensional computerized tomographic renal volumetry as an alternative to scintigraphy in estimating SRF. As computed tomography (CT) angio is done routinely for donors use of the same CT for estimating renal functions can eliminate the radiation from scintigraphy. Methods: In our study, renal volume was estimated on computerized tomographic renal angiography images using Siemens volumetry software by drawing contours manually on images, wherein we found the mean total renal volume to be 212.7 ± 38 CC and mean split renal volume to be 49.76 CC ± 2.86 and 50.23CC ± 2.86 on the right and left side, respectively. Results: This split renal volume was corrected to body mass index and surface area wherein we found significant correlation between renal volume and function when both were corrected to body surface area (P < 0.0001). Conclusion: From our results, it appears that computerized tomographic renal angiography not only depicts anatomy but also can give information about renal function which needs further confirmation.
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Value of ambulatory blood pressure monitoring in potential renal donors - A prospective observational study p. 215
Mital Dipakkumar Parikh, Umapati Hegde, Mohan Rajapurkar, Sishir Gang, Abhijit Konnur, Hardik Patel
Introduction: Hypertension is very common among urban as well as rural population. In our donor selection policy, uncontrolled hypertension or target organ damage is a contraindication to kidney donation. Studies of blood pressure (BP) response to unilateral nephrectomy in kidney donors in short- and long-term are needed. We studied BP in kidney donors by ambulatory BP monitoring (ABPM) and the effect of unilateral nephrectomy on BP in them for 1 year following kidney donation. Methodology: We enrolled 80 consenting kidney donors aged between 20 and 65 years and followed them serially at pre, 6, and 12 months postkidney donation. Estimated glomerular filtration rate (eGFR) was measured using chronic kidney disease exocrine pancreatic insufficiency (CKD EPI) formula. BP was measured in the clinic (sphygmomanometer) and by ABPM (MeditechABPM05). eGFR, two-dimensional echocardiography, ophthalmological fundus examination, and 24 h proteinuria measurement were done at each visit. Results: There was a significant difference in predonation systolic BP by clinic and ABPM (138.07 + 5.5 vs. 117.17 + 10.2; P < 0.001) suggestive of white coat hypertension (WC) effect in 32 donors (40%) which decreased to only 21 (26.25%) donors having WC effect at 12 months of follow-up. There was masked hypertension (MH) in total 3 (3.75%) donors with sustained hypertension (SH) in 10 (12.5%) donors. BP was stable by ABPM till 1-year postdonation. Mean systolic and diastolic BP by ABPM was significantly higher in SH and MH groups as compared to WC and sustained normotensives. Baseline predonation eGFR measured by CKD-EPI was 106.0 + 12.35. eGFR decreased to 80.15 ± 15.76, i.e. 76% of the baseline eGFR. Hypertension by ABPM at baseline was associated with more decrease in the eGFR at 1 year of follow-up particularly in those with age > 50 years and higher body mass index. Proteinuria increased from the baseline value of 82.7 ± 29.94–104.07 ± 49.36 mg/day at 1 year of follow-up. Conclusions: ABPM provides a more accurate and reproducible estimate of BP compared to clinic BP to rule out WC hypertension and MH in kidney donors. Unilateral nephrectomy has no significant impact on kidney function or proteinuria over 1 year.
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Comparison of donor corneas obtained from hospital cornea retrieval program and voluntary eye donation in South India - A prospective study p. 223
Vinitha L Rashme, Naveen Radhakrishnan, Manoranjan Das, Muthiah Srinivasan, N Venkatesh Prajna
Background: The aim of this study was to compare the donor characteristics, quality of tissues, and utilization rate of corneas collected through Hospital cornea retrieval program (HCRP) and voluntary eye donation (VED). Methods: A prospective nonrandomized comparative study of all consecutive donor corneas collected through HCRP and VED during December 2015 to November 2016 was performed. Details of the donor such as age, sex, cause of death, need for medicolegal clearance, death to enucleation time, slit-lamp grading, specular microscopy, and tissue utilization were documented. Results: Nine hundred and eighty-five eyes of 493 donors were included in the study, of which 606 (61.5%) eyes belonged to HCRP and 379 (38.5%) eyes in VED. HCRP donors were significantly younger (HCRP: 43.87 ± 19 years; VED: 72.8 ± 13 years; P < 0.001). Males were more common in HCRP (HCRP: 236, 77.6%; VED: 99, 52.2%; P < 0.001). The most common cause of death was road traffic accident (132, 43.6%) in HCRP and cardiovascular disease (93, 49%) in VED. 73.3% (222) of HCRP donors needed medicolegal clearance. Phakic donor eyes were significantly higher in HCRP (HCRP: 561, 92.6%; VED: 184, 48.6%; P < 0.001). Specular microscopy was possible in 396 (65.3%) eyes of HCRP and 129 (34%) eyes of VED. The mean endothelial cell density was 2931 ± 431.1 in HCRP and 2668.6 ± 381.1 in VED. The tissue utilization rate was significantly higher in HCRP (HCRP: 481, 79.4%; VED: 201, 53%; P < 0.001). Eighty-two percent of endothelial keratoplasty, 78.5% of optical penetrating keratoplasty, and 58% of therapeutic keratoplasty were from HCRP donors. Conclusion: Donor corneas collected through HCRP have higher tissue utilization.
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Tacrolimus therapeutic drug monitoring and correlation with clinical events – A single-center prospective study p. 227
Mayoor V Prabhu, Akash Nayak Karopadi, Sreepada V Subhramanyam, B. H. Santhosh Pai, KS Nayak
Background: Tacrolimus exposure is estimated by trough levels (C0). Recent studies suggest that C0 may not accurately reflect the area under the curve (AUC) and may not correlate with clinical events like acute rejection (AR) and nephrotoxicity. Materials and Methods: In an open, prospective, single-center study, 29 consecutive recipients of renal transplantation underwent C0 along with 2-h (C2), 4-h (C4), and 6-h (C6) estimation of blood tacrolimus levels by enzyme-linked immunosorbent assay, 72 h after initiation with tacrolimus or after a change in its dosage. AUC was estimated by trapezoidal method. C0, C2, C4, and C6 levels were correlated with the AUC. Results: Thirty-six AUC estimations were made over a 2-year period. The best correlate was C6. Correlation coefficients were C0 – 0.868, C2 – 0.788, C4 – 0.839, and C6 – 0.904. C6 values accounted for 79% of the variability of the AUC. Six patients experienced AR, with 5 having C0 within the target range. C6 values correlated best with AUC in these patients (C0 – 0.970, C2 – 0.833, C4 – 0.942, and C6 – 0.970). This was statistically significant. Three patients developed tacrolimus toxicity. In these patients, the correlation coefficients were C0 – 0.551, C2 – 0.556, C4 – 0.77, and C6 – 0.941. By regression analysis, we developed predictive equations. The equation AUC = 12.126 + 2.81 × C0 + 2.92 × C6 best predicted the AUC. Conclusions: Overall C6 levels were more predictive of the AUC, accurately predicting AR and nephrotoxicity. Incorporating C6 may improve tacrolimus therapeutic drug monitoring.
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Posttransplant renal allograft dysfunction – A retrospective observational study p. 232
Mathew George Kunthara, Manisha Sahay, Hakim Imran Hussain, Kiranmai Ismal, P Sharmas Vali, Anuradha Kavadi, B Vikram Kumar
Background: In India, a large number of end-stage renal disease patients are undergoing renal replacement therapy. A successful renal transplantation relives the burden of dialysis with improved quality of life and a productive life thereafter. This also reduces the cost of health care to the government and the society. Graft dysfunction is an important cause of graft loss.The objective of this retrospective study is to evaluate the graft dysfunction and its impact on patient and graft survival. Methods: We did a retrospective record-based analysis of 83 cases (including both deceased and live-related renal transplants) from 2014 to 2019 who were on triple immunosuppression (tacrolimus, mycophenolate mofetil, and steroids) as maintenance therapy. Patients who had graft dysfunction, underwent graft biopsy and were analyzed subsequently. Results: The most common causes for graft dysfunction on biopsy were acute rejection, acute tubular injury, and calcineurin inhibitor toxicity. About 39% of the patients had infections, predominantly bacterial and viral infections. The rejections were associated with poor patient survival (statistically significant). The overall patient survival at our center after 1 year and 3 years was 88% and 84%, respectively, while the death-censored graft survival was 86% and 81%, respectively. Conclusion: In our center, following renal transplantation, patients had a fairly successful outcome. However, early detection and prompt management of the graft dysfunction can improve the graft and the patient survival.
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Peripheral lymphocyte subsets in acute cellular rejection in living donor liver-transplant recipients: A prospective observational study p. 241
Pradeep Kumar, Viniyendra Pamecha, Archana Rastogi, Rajeev Khanna, Nirupma Trehanpati
Introduction: The aim of the study was to assess the peripheral blood lymphocyte subsets as immune markers for acute cellular rejection (ACR) in the living donor liver-transplant (LDLT) recipients using high-dimensional flow cytometry. Materials and Methods: This is a prospective observational study in which 19 LDLT recipients undergoing liver biopsy for suspected rejection were enrolled after informed and written consent. They were divided into two groups as rejection group (11/19) and no rejection group (6/19). In addition to this, nine healthy subjects were also enrolled as controls. Biochemical and immune parameters were analyzed among these groups. Results: It was observed that hematocrit, total protein, and serum albumin levels were significantly higher in rejection group as compared to no rejection group (P = 0.021, 0.006, and 0.044, respectively), whereas aspartate transaminase was significantly lower in rejection group compared to no rejection group (P = 0.027). It was seen that central memory (CM) helper T (TH) cells and CM cytotoxic T (TC) cells were significantly lower in no rejection group when compared to healthy controls (P = 0.02 and 0.009, respectively). The effector TH cells and TH1 cells were significantly higher in the rejection group when compared to healthy controls (P = 0.03 and 0.04, respectively). However, the effector CD8+ T cell and memory B cell subsets were significantly higher in rejection and no rejection group compared with healthy controls (P = 0.03, 0.01 and P = 0.02, 0.009 respectively). The activated regulatory T cells (TREG) and plasmablasts were significantly higher in no rejection group when compared with healthy control (P = 0.038 and 0.016, respectively). The naïve B cells were significantly lower in rejection and no rejection group compared to healthy controls (P = 0.001 and 0.01, respectively). However, when immune profile was compared among the rejection and no rejection group, we could not arrive at statistically significant results owing to the small sample size. Conclusion: The data in this study show that there is difference in immune profile of lymphocyte subsets among rejection and no rejection groups compared to healthy controls and hence can be used to characterize these patients. The promising immune subsets that can serve as biomarkers for ACR post-LDLT are TH1 cells, CM TH cells, effector TH cells, CM TC cells, effector TC cells, activated TREG cells, naïve B cells, memory B cells, and plasmablasts.
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Transplant renal artery stenosis: urgent and judicious to avoid disaster; A narrative review p. 251
Nalaka Gunawansa, David Aziz, Ajay Sharma, Ahmed Halawa
Transplant renal artery stenosis (TRAS) remains a dreaded complication of renal transplant surgery with potentially devastating sequelae. TRAS occurring early in the posttransplant period is mainly due to technical faults related to the graft implantation process. Late TRAS, in contrast, is more the result of either progressive atherosclerotic disease in the recipient vasculature or immunological, infective, and drug toxicity-related intimal injury. The clinical presentation may range from asymptomatic incidentally detected lesions to frank stenosis causing refractory hypertension or graft dysfunction. Accurate diagnosis with prompt intervention in the clinically significant lesions is the hallmark of successful management in TRAS, thereby averting the possible risk of renal artery thrombosis and graft loss.
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How to set a heart transplantation unit in India - A narrative review p. 257
TK Jayakumar, Joseph Thomas, Dhaval Bhimani
Cardiovascular diseases (CVDs) have become the leading cause of mortality in India. This epidemiological transition is largely because of the increase in the prevalence of CVDs and CVD risk factors in India. In 2016, the estimated prevalence of CVDs in India was estimated to be 54.5 million. Heart failure (HF) is a major health problem in India with a postadmission mortality of 20%–30%. Heart transplant is the final treatment for HF if intractable to medical management. Number of heart transplantations done in India is still very less compared to the disease burden and may be attributed to less awareness for organ donation in India. As the number of heart transplantation is increased drastically in the past decade, we need to have proper information about heart transplantation program in India. This is our attempt to simplify information regarding heart transplantation for cardiothoracic units planning to start such a program.
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Transplantation of human organs act: Act of transplantation – Time to act on the act! - Narrative review p. 260
Manjusha Yadla
When the transplant act was brought in by the Central Government of India, the number of centers performing organ transplants and the number of patients undergoing transplants were much lesser compared to the present-day statistics. Knowing that the shortage of organs is the driving force behind illegal organ trade, strategies for legal and ethical expansion of the donor pool should be framed. Although Transplantation of Human Organs Act (Amended 2011 and Transplantation of Human Organs and Tissues Act Rules 2014) included swap transplantation and laid down certain rules for empowerment of deceased donor organ transplantation, certain changes are the need of the hour to expand the donor pool. Safeguarding the physicians' security and the recipient and donor rights is of prime concern in the process of organ transplantation. The present Act needs certain changes which clearly define the legal definition of brain death, legal issues involved in brain death, ethical and legal means of expansion of donor pool, and objective assessment of altruism.
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Seizure and hemichorea post renal transplantation: A recipient with heterogeneous risk factors - A case report p. 266
Appu Jose, Deepa Usulumarty, Viswanath Billa, Kuldeep Singh
Kidney transplantation is the preferred renal replacement therapy for patients with end-stage kidney disease. However, these patients are vulnerable to multiple complications arising out of immunosuppression, comorbidities, and opportunistic infections. We report a case of hemichorea in a transplant recipient. This patient had concurrent polycythemia, new-onset diabetes after transplantation, and was on calcineurin-based immunosuppression. The magnetic resonance imaging ascribed her hemichorea to Non ketotic hyperglycemia (NKH) which recovered completely with prompt treatment of the hyperglycemia.
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Unusual presentation of posttransplant renal artery stenosis - A case report p. 269
Sashi Kiran Annavarajula, B Suryaprakash, D Kashinatham, Pawan Poddar
Transplant renal artery stenosis (TRAS) is a well-recognized and potentially treatable cause of early graft dysfunction. Recognition of TRAS can sometimes be difficult, and the presentation may mimic acute allograft rejection. A high index of suspicion along with arteriography is crucial in early recognition and management.
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Organ transplantation, immunosuppressant therapy, and management dilemma in drug-induced psychiatric manifestations: Lessons learned from a case report p. 272
Shivani Dua, Jayaprakash Russell Ravan, Vijay Raj Pratheek, J Ipsita Pattnaik, Sai P Sahoo
Solid organ transplantation is the intervention of choice for end-stage renal disease burdening the patient and care givers. Posttransplant patients receive immunosuppression therapy to prevent graft rejection which might lead to psychiatric side effects induced by the drugs, which require psychotropics for symptomatic relief. We present the case of a young man who developed tacrolimus-induced psychosis and management dilemma due to the drug interactions. Risperidone or haloperidol, which is usually given for acute management of psychotic symptoms, is contraindicated due to the interactions with immunosuppressant therapy. In consultation–liaison psychiatry, it is imperative to know the interactions between psychotropics and transplant medications. We also discuss in detail the posttransplant psychiatric conditions and safer alternative psychotropics for different psychiatric conditions in view of potential drug–drug interaction of other medications with that of immunosuppressants.
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Varying presentations of pulmonary nocardiosis in kidney transplant recipients - Case series p. 275
Kumar Shabeen, Sandeep Sreedharan, Zachariah Paul Polachirakkal, Nandita Shashindran, Anil Mathew, V Anil Kumar, George Kurian, Rajesh R Nair
Infections continue to be a significant cause of morbidity and mortality after solid organ transplantation. Early identification of the pathogenic organism is extremely important as the disease process might progress rapidly resulting in fatality. In this case series, we describe varying presentations of pulmonary nocardiosis, an uncommon opportunistic bacterial infection that often complicates the diagnosis of pneumonia, especially in immunocompromised patients. Although cough, fever, expectoration and breathlessness are the most common symptoms of pulmonary nocardiosis, they can also manifest as night sweats, weight loss and malaise. Some are incidentally diagnosed while being evaluated for other causes. Radiological features are also non-specific, usual findings being irregular nodules, cavitation, reticulo nodular diffuse pneumonia and pleural effusions. Bronchoalveolar lavage has the best diagnostic yield, but may have to be repeated several times to confirm a diagnosis, if the index of suspicion is high. Initial therapy with high dose trimethoprim- sulfamethoxazole is found to be effective in most of the cases. Duration of treatment should be a minimum of 6 months, and at least 12 months if central nervous system is affected. Other agents used for treatment include imipenem, minocycline, third generation cephalosporins, linezolid and amikacin. A high index of suspicion, with aggressive evaluation in an immunosuppressed individual will enable an early diagnosis, leading to prompt treatment and limit dissemination of disease thus preventing fatality.
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Pretransplant compatibility tests in kidney transplants: Significance of adding HLA bead-based assay to direct cell-based cross-match assays - A case report p. 279
Chhavi Rajvanshi, Aseem K Tiwari, Swati Pabbi, Geet Aggarwal, Abhishek Saini, Rajni Chauhan, Simmi Mehra, Poonam Kumari
Pre-transplant compatibility work-up has evolved tremendously from conventional CDC only to CDC with more sensitive FCXM testing with bead-based assays (LMX and SAB). Detection of alloantibodies is one of the major objective in work-up algorithm. Conventionally cell-based tests were used, if both are negative, hospital usually proceeds for transplantation. If one of the screening tests (CDC/FCXM) is or both (CDC and FCXM) screening tests are positive, antibody identification is performed on Luminex platform to determine DSA by virtual cross-match. However, cell-based tests have their limitations. Here, we described a case which could have gone unnoticed if HLA bead-based assay was not there and could have triggered AMR (Antibody mediated rejection) as detected antibody (DRB1*07:01; BCM is 16416) was DSA.
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Chronic allograft nephropathy with proteinuria Highly accessed article p. 282
Praveen Kumar Etta, Thatipamula Madhavi
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De novo membranous nephropathy in an allograft p. 284
Swarnalata Gowrishankar
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