Browsing by Author "Sharfuddin, Asif"
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Item Adrenocorticotropic Hormone in the Treatment of Focal Segmental Glomerulosclerosis Following Kidney Transplantation(Elsevier, 2019-07) Grafals, Mónica; Sharfuddin, Asif; Medicine, School of MedicineThis retrospective study examined the effect of adrenocorticotropic hormone therapy on remission of recurrent focal segmental glomerulosclerosis (FSGS) in patients with history of kidney transplant (KT) treated at 2 transplant centers. Patients with biopsy-confirmed FSGS following KT who received Acthar Gel (Mallinckrodt ARD, Bedminster, New Jersey, United States) treatment for ≥1 month were eligible. A total of 14 patients with idiopathic FSGS were included. Acthar Gel treatment resulted in complete remission of FSGS in 3 patients and partial remission in 2 patients for a total treatment response rate of 36% (5/14) of patients. Among patients showing complete or partial remission, Acthar Gel treatment duration ranged from 6 months to 2 years and 60% (3/5 patients) had serum creatinine ≤ 2 mg/dL at the start of Acthar Gel treatment. Patient outcomes suggest Acthar Gel may be an effective and tolerable treatment for recurrent FSGS in patients with history of KT. Early initiation of Acthar Gel treatment and therapy duration of at least 6 months may be needed for optimal response to Acthar Gel in patients with history of KT and recurrent FSGS.Item Cell-Free DNA and Active Rejection in Kidney Allografts(American Society of Nephrology, 2017-07) Bloom, Roy D.; Bromberg, Jonathan S.; Poggio, Emilio D.; Bunnapradist, Suphamai; Langone, Anthony J.; Sood, Puneet; Matas, Arthur J.; Mehta, Shikha; Mannon, Roslyn B.; Sharfuddin, Asif; Fischbach, Bernard; Narayanan, Mohanram; Jordan, Stanley C.; Cohen, David; Weir, Matthew R.; Hiller, David; Prasad, Preethi; Woodward, Robert N.; Grskovic, Marica; Sninsky, John J.; Yee, James P.; Brennan, Daniel C.; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators; Medicine, School of MedicineHistologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.Item Characteristics associated with access to kidney transplantation services in the Ohio River Valley(2024-04-26) Kelty, Catherine; Buford, Jade; Drewry, Kelsey; Adebiyi, Oluwafisayo; Sharfuddin, Asif; Fridell, Jonathan; Sher, Jawad; Huml, Anne; Moe, Sharon; Patzer, RachelItem Early Enterococcus-associated acute postinfectious glomerulonephritis after kidney transplant.(Oxford University Press, 2014-08) Tandon, Teena; Mujtaba, M.; Mishler, Dennis; Phillips, Carrie; Sharfuddin, Asif; Department of Medicine, IU School of MedicinePostinfection as an etiology for glomerulonephritis (GN) is rarely described in post-transplant recipients and may be due to impaired immune response. It is also possible that such cases are not biopsied or not reported. There are rare case reports in the literature. We report here a rare first case of Enterococcus-related postinfectious GN in a transplant recipient seen in our center.Item Epidemiology and Risk Factors for Invasive Fungal Infections in Pancreas Transplant in the Absence of Postoperative Antifungal Prophylaxis(Oxford University Press, 2023-09-26) Zachary, Jessica; Chen, Jeanne M.; Sharfuddin, Asif; Yaqub, Muhammad; Lutz, Andrew; Powelson, John; Fridell, Jonathan A.; Barros, Nicolas; Medicine, School of MedicineBackground: Invasive fungal infections (IFIs) remain a rare yet dreaded complication following pancreas transplantation. Current guidelines recommend antifungal prophylaxis in patients with 1 or more risk factors. At our center, single-dose antifungal prophylaxis is administered in the operating room but none subsequently, regardless of risk factors. Here we evaluate the 1-year incidence, outcome, and risk factors associated with IFI following pancreas transplantation. Methods: A retrospective, single-center cohort study was conducted in patients who underwent pancreas transplantation between 1 January 2009 and 31 December 2019. Records were manually reviewed, and cases were adjudicated using consensus definitions. The 1-year cumulative incidence, mortality, and risk factors were analyzed by Kaplan-Meier method and differences between populations were assessed with Fisher test and Mann-Whitney U test. Results: Three hundred sixty-nine recipients were included. Twelve IFIs were identified: candidiasis (8), aspergillosis (2), histoplasmosis (1), and cryptococcosis (1). Intra-abdominal infections were the most common presentation (5), followed by bloodstream infections (3), disseminated disease (2), pulmonary disease (1), and invasive fungal sinusitis (1). Median time to IFI was 64 days (interquartile range, 30-234 days). One-year cumulative incidence was 3.25% (95% confidence interval, 1.86%-5.65%). There were no significant differences between patients with or without IFI regarding type of transplant (P = .17), posttransplant dialysis (P = .3), rejection (P = .5), cytomegalovirus serostatus (P = .45), or reoperation (P = .19). For patients with IFI, the 1-year graft and patient survival rates were 58% versus 95% (P < .0001) and 75% versus 98.6% (P < .001), respectively. Conclusions: Our study suggests that the use of a single-dose antifungal prophylaxis administered in the operating room but none subsequently does not result in an increased incidence of IFI following pancreas transplantation.Item Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience(Wiley, 2018) Cheng, Yao-Wen; Phelps, Emmalee; Ganapini, Vincent; Khan, Noor; Ouyang, Fangqian; Xu, Huiping; Khanna, Sahil; Tariq, Raseen; Friedman-Moraco, Rachel J.; Woodworth, Michael H.; Dhere, Tanvi; Kraft, Colleen S.; Kao, Dina; Smith, Justin; Le, Lien; El-Nachef, Najwa; Kaur, Nirmal; Kowsika, Sree; Ehrlich, Adam; Smith, Michael; Safdar, Nasia; Misch, Elizabeth Ann; Allegretti, Jessica R.; Flynn, Ann; Kassam, Zain; Sharfuddin, Asif; Vuppalanchi, Raj; Fischer, Monika; Medicine, School of MedicineFecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti‐CDI antibiotics, respectively. Ninety‐four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT‐related adverse events (AE) occurred in 22.3% of cases, mainly comprising self‐limiting conditions including nausea, abdominal pain, and FMT‐related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT‐related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus‐seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non‐CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.Item Long-term outcomes of transplant recipients referred for angiography for suspected transplant renal artery stenosis(Wiley, 2015-09) Ali, Anum; Mishler, Dennis; Taber, Tim; Agarwal, David; Yaqub, Muhammad; Mujtaba, Muhammad; Goggins, William; Sharfuddin, Asif; Department of Medicine, IU School of MedicineOur aim was to study the long-term outcomes of all transplant recipients who underwent angiography for suspected TRAS at our institution. The patients were divided into TRAS+ve and TRAS−ve groups based upon angiographically confirmed results. TRAS was confirmed in 58.1% of 74 patients with median time of 8.9 months. Primary angioplasty alone was performed in 56% of patients with TRAS, while the remaining had PTA with stent (PTAS). There was reduction in systolic and diastolic BP (165 ± 19–136 ± 15 mmHg and 82 ± 14 mmHg to 68 ± 12 mmHg; p < 0.05) and number of antihypertensive drugs (3.5 ± 0.9–2.7 ± 1.0; p < 0.05). Overall, graft survival and patient survival from time of transplant were similar in both groups. Graft function was similar for the patients with treated TRAS+ve as compared to TRAS−ve over time. Graft survival and patient survival when compared to an age- and year of transplant-matched cohort control group were also similar. In conclusion, angiography for suspected TRAS is more likely to yield a confirmatory result early in the transplant course as compared to late. Treatment of TRAS in these patients had sustained long-term graft function. Alternative etiologies of HTN and graft dysfunction should be sought for recipients further out from transplant.Item Operational challenges in the COVID‐19 era: Asymptomatic infections and vaccination timing(Wiley, 2021-11) Axelrod, David A.; Ince, Dilek; Harhay, Meera N.; Mannon, Roslyn B.; Alhamad, Tarek; Cooper, Matthew; Josephson, Michelle A.; Caliskan, Yasar; Sharfuddin, Asif; Kumar, Vineeta; Guenette, Alexis; Schnitzler, Mark A.; Ainapurapu, Sruthi; Lentine, Krista L.; Medicine, School of MedicineThe coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid test (NAT) for COVID-19 is unclear as this may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of prospective data, transplant professionals at U.S. adult kidney transplant centers were surveyed to determine community practice (N: 92 centers, capturing 40.8% of centers and 56.6% of transplants performed). The majority (96.8%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 31.6% of centers proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with transplant in patients with positive tests due to presumed viral shedding. Furthermore, very few centers are requiring COVID-19 vaccination prior to transplantation despite early evidence suggesting reduced immunogenicity in transplant patients on immunosuppression.Item Patient and Graft Survival Outcomes During 2 Eras of Immunosuppression Protocols in Kidney Transplantation: Indiana University Retrospective Cohort Experience(Elsevier, 2021-12) Adebiyi, Oluwafisayo; Umukoro, Peter; Sharfuddin, Asif; Taber, Tim; Chen, Jeanne; Lane, Kathleen A.; Li, Xiaochun; Goggins, Williams; Yaqub, Muhammad S.; Biostatistics, School of Public HealthBackground Since 1964 when Indiana University performed its first kidney transplant, immunosuppression protocol was steroid-based until 2004 when steroid-free immunosuppression protocol was adopted. We describe clinical outcomes on our patients administered early steroid withdrawal (ESW) protocol (5 days) compared with our historical cohort (HC), who were on chronic steroid-based immunosuppression. Methods We performed a retrospective study evaluating kidney transplant recipients between 1993 and 2003 (HC, n = 1689) and between 2005 and 2016 (ESW cohort, n = 2097) at the Indiana University program, with a median follow-up of 10.5 years and 6.1 years, respectively. Primary outcomes were patient and death-censored graft survival at 1, 3, and 5 years in both study cohorts. Secondary outcomes were 1-year rates of biopsy-proven acute rejection; graft function at 1, 3, and 5 years; and risk of post-transplant infection (BK virus and cytomegalovirus) in the ESW cohort. Cox proportional model and Kaplan-Meier estimates were used to estimate survival probabilities. Fisher exact tests were used to compare episodes of acute rejection in the ESW cohort. Results No difference was observed in patient survival between the ESW and HC cohorts (P = .13). Compared with the ESW cohort, death-censored graft survival was significantly worse in the HC (5 year: 86.4% vs 90.6%, log-rank P < .001). One-year acute rejection reported in the ESW cohort alone was 15.7% and significantly worse in Black patients and younger patients (P < .05). Conclusions In this sizeable single-center cohort study with significant ethnic diversity, ESW is a viable alternative to steroid-based immunosuppression protocol in kidney transplant recipients.Item Re-exposure to beta cell autoantigens in pancreatic allograft recipients with pre-existing beta cell autoantibodies(Wiley, 2015-11) Mujtaba, Muhammad Ahmad; Fridell, Jonathan; Book, Benita; Faiz, Sara; Sharfuddin, Asif; Wiebke, Eric; Rigby, Mark; Taber, Tim; Department of Medicine, IU School of MedicineRe-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p < 0.0001), 12 months (p < 0.0001), and from post-6 to post-12 months (p = 0.0002) was seen. No new BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.