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Item Challenges of the Pioneer Renal Transplants at Moi Teaching and Referral Hospital, Eldoret, Kenya(Association of Kenya Physicians, 2007) Ganda, B. K.; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)History I –Theatre: • Eldoret Dist Hosp built in 1926 • 1926-1999. One operation table • 2000-Majaliwa Theatre 4 tables; intensive care room as ICU Indiana Community • 2007-2 More operation tables. Indiana Comm.Item Effect of kidney donation on bone mineral metabolism(Public Library of Science, 2020-07-07) Hiemstra, Thomas F.; Smith, Jane C.; Lim, Kenneth; Xu, Dihua; Kulkarni, Shreya; Bradley, J. Andrew; Paapstel, Kaido; Schoenmakers, Inez; Bradley, John R.; Tomlinson, Laurie; McEniery, Carmel M.; Wilkinson, Ian B.; Medicine, School of MedicineKidney donation results in reductions in kidney function and lasting perturbations in phosphate homeostasis, which may lead to adverse cardiovascular sequelae. However, the acute effects of kidney donation on bone mineral parameters including regulators of calcium and phosphate metabolism are unknown. We conducted a prospective observational controlled study to determine the acute effects of kidney donation on mineral metabolism and skeletal health. Biochemical endpoints were determined before and after donation on days 1, 2 and 3, 6 weeks and 12 months in donors and at baseline, 6 weeks and 12 months in controls. Baseline characteristic of donors (n = 34) and controls (n = 34) were similar: age (53±10 vs 50±14 years, p = 0.33), BMI (26.3±2.89 vs 25.9±3.65, p = 0.59), systolic BP (128±13 vs 130±6 mmHg, p = 0.59), diastolic BP (80±9 vs 81±9 mmHg, p = 0.68) and baseline GFR (84.4±20.2 vs 83.6±25.2 ml/min/1.73m2, p = 0.89). eGFR reduced from 84.4±20.2 to 52.3±17.5 ml/min/1.73m2 (p<0.001) by day 1 with incomplete recovery by 12 months (67.7±22.6; p = 0.002). Phosphate increased by day 1 (1.1(0.9–1.2) to 1.3(1.1–1.4) mmol/L, p <0.001) but declined to 0.8(0.8–1.0) mmol/L (p<0.001) before normalizing by 6 weeks. Calcium declined on day 1 (p = 0.003) but recovered at 6 weeks or 12 months. PTH and FGF-23 remained unchanged, but α-Klotho reduced by day 1 (p = 0.001) and remained low at 6 weeks (p = 0.02) and 1 year (p = 0.04). In this study, we conclude that kidney donation results in acute disturbances in mineral metabolism characterised by a reduced phosphate and circulating α-Klotho concentration without acute changes in the phosphaturic hormones FGF23 and PTH.Item Interindividual Variability in Lymphocyte Stimulation and Transcriptomic Response Predicts Mycophenolic Acid Sensitivity in Healthy Volunteers(Wiley, 2020-11) Collins, Kimberly S.; Cheng, Ying-Hua; Ferreira, Ricardo M.; Gao, Hongyu; Dollins, Matthew D.; Janosevic, Danielle; Khan, Nida A.; White, Chloe; Dagher, Pierre C.; Eadon, Michael T.; Medicine, School of MedicineMycophenolic acid (MPA) is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. MPA inhibits IMPDH2 within stimulated lymphocytes, reducing guanosine synthesis. Despite the widespread use of MPA, interindividual variability in response remains with rates of allograft rejection up to 15% and approximately half of individuals fail to achieve complete remission to lupus nephritis. We sought to identify contributors to interindividual variability in MPA response, hypothesizing that the HPRT1 salvage guanosine synthesis contributes to variability. MPA sensitivity was measured in 40 healthy individuals using an ex vivo lymphocyte viability assay. Measurement of candidate gene expression (n ± 40) and single‐cell RNA‐sequencing (n ± 6) in lymphocytes was performed at baseline, poststimulation, and post‐MPA treatment. After stimulation, HPRT1 expression was 2.1‐fold higher in resistant individuals compared with sensitive individuals (P ± 0.049). Knockdown of HPRT1 increased MPA sensitivity (12%; P ± 0.003), consistent with higher expression levels in resistant individuals. Sensitive individuals had higher IMPDH2 expression and 132% greater stimulation. In lymphocyte subpopulations, differentially expressed genes between sensitive and resistant individuals included KLF2 and LTB. Knockdown of KLF2 and LTB aligned with the predicted direction of effect on proliferation. In sensitive individuals, more frequent receptor‐ligand interactions were observed after stimulation (P ± 0.0004), but fewer interactions remained after MPA treatment (P ± 0.0014). These data identify a polygenic transcriptomic signature in lymphocyte subpopulations predictive of MPA response. The degree of lymphocyte stimulation, HPRT1, KLF2, and LTB expression may serve as markers of MPA efficacy.Item Kidney Transplantation From Donors with Hepatitis B(International Scientific Literature, 2016-04-28) Veroux, Massimiliano; Ardita, Vincenzo; Corona, Daniela; Giaquinta, Alessia; Ekser, Burcin; Sinagra, Nunziata; Zerbo, Domenico; Patanè, Marco; Gozzo, Cecilia; Veroux, Pierfrancesco; Department of Surgery, IU School of MedicineThe growing demand for organ donors to supply the increasing number of patients on kidney waiting lists has led most transplant centers to develop protocols that allow safe use of organs from donors with special clinical situations previously regarded as contraindications. Deceased donors with previous hepatitis B may be a safe resource to increase the donor pool even if there is still controversy among transplantation centers regarding the use of hepatitis B surface antigen-positive donors for renal transplantation. However, when allocated to serology-matched recipients, kidney transplantation from donors with hepatitis B may result in excellent short-term outcome. Many concerns may arise in the long-term outcome, and studies must address the evaluation of the progression of liver disease and the rate of reactivation of liver disease in the recipients. Accurate selection and matching of both donor and recipient and correct post-transplant management are needed to achieve satisfactory long-term outcomes.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 Pre-transplant antibody screening and anti-CD154 costimulation blockade promote long-term xenograft survival in a pig-to-primate kidney transplant model(Wiley Blackwell (Blackwell Publishing), 2015-05) Higginbotham, Laura; Mathews, Dave; Breeden, Cynthia A.; Song, Mingqing; Farris, Alton Brad; Larsen, Christian P.; Ford, Mandy L.; Lutz, Andrew J.; Tector, Matthew; Newell, Kenneth A.; Tector, A. Joseph; Adams, Andrew B.; Department of Surgery, IU School of MedicineXenotransplantation has the potential to alleviate the organ shortage that prevents many patients with end-stage renal disease from enjoying the benefits of kidney transplantation. Despite significant advances in other models, pig-to-primate kidney xenotransplantation has met limited success. Preformed anti-pig antibodies are an important component of the xenogeneic immune response. To address this, we screened a cohort of 34 rhesus macaques for anti-pig antibody levels. We then selected animals with both low and high titers of anti-pig antibodies to proceed with kidney transplant from galactose-α1,3-galactose knockout/CD55 transgenic pig donors. All animals received T-cell depletion followed by maintenance therapy with costimulation blockade (either anti-CD154 mAb or belatacept), mycophenolate mofetil, and steroid. The animal with the high titer of anti-pig antibody rejected the kidney xenograft within the first week. Low-titer animals treated with anti-CD154 antibody, but not belatacept exhibited prolonged kidney xenograft survival (>133 and >126 vs. 14 and 21 days, respectively). Long-term surviving animals treated with the anti-CD154-based regimen continue to have normal kidney function and preserved renal architecture without evidence of rejection on biopsies sampled at day 100. This description of the longest reported survival of pig-to-non-human primate kidney xenotransplantation, now >125 days, provides promise for further study and potential clinical translation.Item Renal relevant radiology: imaging in kidney transplantation(American Society of Nephrology, 2014-02) Sharfuddin, Asif; Department of Medicine, IU School of MedicineKidney transplantation can be associated with various complications that vary from vascular complications to urologic disorders to immunologic adverse effects. In evaluating the recipient with graft dysfunction, clinicians can choose among several imaging modalities, including ultrasonography, nuclear medicine studies, computed tomography, and magnetic resonance imaging. This review discusses the evaluation of the kidney transplant recipient using these imaging procedures, emphasizing the clinical diagnostic utility and role of each modality. A kidney biopsy is often required as a gold standard for diagnostic purposes. However, because of the inherent risks of a kidney biopsy, noninvasive imaging in diagnosing causes of graft dysfunction is a highly desired tool used and needed by the transplant community. Because the diagnostic accuracy varies depending on the time course and nature of the transplant-related complication, this review also addresses the advantages and limitations of each modality. The recent advances in kidney transplant imaging techniques and their clinical implications are also discussed.Item Renal Transplant at MTRH(Association of Kenya Physicians, 2007) Owiti, M. O. G.; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)J.A. 48 yrs male - Diabetic since July 1997, on insulin. Crf & high Bp-2004.urea=57.3, crt=1040. Lt kid-7.27x3.62, rt kid8.51x3.34cm, loss of cmd. Haemodialysis x2 wkly till last two wksx3. While on treatment Bp=150/100, pulse78/min. on Adalat 20mg b.d,lasix 80mg od, captopril 25mg b.d,ca-sandoz i.o.d, recormon 2000i.u x2wkly, venofer 100 wkly, ranitidine150 mgo.d. N.C. 17 yrs female - Facial puff, head ache,oliguria, epigastric and bil loin Painsx3/52. 03.08.2004. Post herbal use. Abortion –pph, 07.06.04, post abortal psychosis. Bp220/110mmhg, hb=7.6g/dl, Op=600mls, ip=1.5l.