Dennis P Mishler

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States

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Publications (14)

  • [Show abstract] [Hide abstract] ABSTRACT: Outcomes of kidney Re-Transplant Recipients (RTR) were compared to Primary Recipients (FTR) from paired donor kidneys. OPTN database was used to identify deceased donors (n=6,266) who donated one kidney to a RTR and the mate kidney to a FTR between January 2000 to December 2010. As compared to FTR, RTR were younger (45 vs 52 years, p<0.001) and had higher proportion of PRA >80 (25% vs 7%, p<0.001). There were higher 0 mismatches in RTR (19% vs 16%, p<0.001). There were more pre-emptive transplants in RTR (24% vs 21%, p=0.002). Delayed graft function (28% vs 25%, P=0.007) was higher in RTR. Patient survival was similar in FTR and RTR groups at 1, 3 and 5 years (95.7%, 90.2% and 82.5% vs 95.2%, 89.8% and 82.7%). Allograft survival rates were higher in FTR group compared to RTR group at 1, 3 and 5 years (91.1%, 82.4% and 70.9% vs 87.8%, 77.4% and 66.1% p<0.001). Death-censored allograft survival rates were higher in FTR group at 1, 3 and 5 years (91.3%, 82.7% and 71.4% vs 88%, 77.7% and 66.5% p<0.001). In today's era of modern immunosuppression, graft survival in RTR has improved but remains inferior to FTR when controlling for donor factors. This article is protected by copyright. All rights reserved.
    Article · Feb 2016 · Clinical Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: Angiosarcomas are extremely rare malignant tumors of vascular origin. We describe a 63-year-old recipient after a kidney transplant who had an angiosarcoma in the lower extremity that presented after new-onset deep venous thrombosis and was not associated with any fistula. There was rapid progression to metastasis and death. We reviewed the literature of this rare malignant tumor in kidney transplant patients.
    Article · Jul 2015
  • Anum Ali · Dennis Mishler · Tim Taber · [...] · Asif Sharfuddin
    [Show abstract] [Hide abstract] ABSTRACT: Our 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 to 136±15 mm Hg and 82 ± 14mm Hg to 68 ± 12 mm Hg;p<0.05) and number of anti-hypertensive drugs (3.5±0.9 to 2.7±1.0;p<0.05). Overall graft and patient survival from time of transplant was similar in both groups. Graft function was similar for the patients with treated TRAS+ 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 was 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Article · Jun 2015 · Clinical Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: Post-kidney transplant recurrence of FSGS is a major problem. AT1R is expressed on podocyte; its expression is elevated in the proteinuric state. Using an ELISA based assay we tested pre-transplant sera of 28 patients with history of idiopathic FSGS for anti-AT1Rlevels and serum soluble urokinase-type plasminogen activator receptor (suPAR) as a biomarker for risk of recurrence of FSGS. Sera from 11 patients with polycystic kidney disease [PKD] were used as controls. Twelve patients had biopsy proven post-transplant FSGS recurrence at 1.5 months. No difference was found in the pre-transplant suPAR levels of FSGS patients (5993±2292 pg. /mL) vs. PKD (7334±4538pg. /mL), (p= 0.23). Serum suPAR levels in patients with FSGS recurrence (5786±1899 pg. /mL) vs. no FSGS recurrence (6149±2598 pg. /mL) (p= 0.69) were not different. Anti-AT1Rlevels in patients with FSGS were 12.66±11.85 U/mL vs. 8.69±6.52 U/mL in PKD (p= 0.32), however, a difference was found in patients with and without FSGS recurrence 20.41±14.36 U/ml 6.84±4.181 U/mL, respectively (p<0.01). Area under curve for suPAR and anti-AT1Rto predict post-transplant FSGS recurrence was 0.51 and 0.84 respectively. Pre-transplant anti-AT1R levels appear to be a helpful biomarker in identifying patients at high risk of post-transplant FSGS recurrence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Article · May 2015 · Clinical Transplantation
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    Teena Tandon · M. Mujtaba · Dennis Mishler · [...] · Asif Sharfuddin
    Full-text Article · Jul 2014 · CKJ: Clinical Kidney Journal
  • [Show abstract] [Hide abstract] ABSTRACT: IntroductionLiving donor evaluation involves imaging to determine the choice of kidney for nephrectomy. Our aim was to study the diagnostic accuracy and correlation between CT based volume measurements and split renal function as measured by nuclear renography in potential living donors and its impacton kidney selection decision.Methods We analyzed 190 CT-based volume measurements in healthy donors, of which 65 donors had a radionuclide study performed to determine split renal function.ResultsThere were no differences in demographics, anthropometric measurements, total volumes, eGFR, creatinine clearances between those who required a nuclear scan and those who did not. There was a significant correlation between CT volume measurement based split renal function and nuclear scan based split renal function (Pearson Coefficient r 0.59; p<0.001). Furthermore, selective nuclear based split renal function allowed careful selection of donor nephrectomy leaving the donor with the higher functioning kidney in most cases. There was also a significantly higher number of right sided nephrectomies selected after nuclear based split renal function studies.ConclusionCT based volume measurements in living donor imaging has sufficient correlation with nuclear based split renal function. Selective use of nuclear scan based split renal function allows careful selection for donor nephrectomy.This article is protected by copyright. All rights reserved.
    Article · Mar 2014 · Clinical Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: Kidney transplantation faces many challenges not the least of which is the presence of pre-formed HLA antibodies. At our institution, we have used a combination of methods to immunomodulate sensitized patients. Most recently, this has been attempted with a combination of immunoglobulin (IVIG) and rituximab (Rituxan; Genetech, CA, USA). A total of 31 patients were followed for up to one yr following treatment with IVIG (2 gm/kg on day 1 and day 30) and rituximab (1 g - day 15). Antibody levels were followed serially at designated time points via solid-phase single-antigen beads (SAB) method (One Lambda, Inc., Canoga Park, CA, USA). Concentration of antibodies was based on median fluorescence intensity (MFI). The majority of patients had both class I and class II antibodies (79%). Our results showed that this protocol appeared to be patient and antibody specific. The most pronounced MFI reduction in antibodies occurred within the 30- to 100-d period post-treatment. Calculated panel-reactive antibodies decreased but rebound tended to occur by 104 d after antibody MFI nadir. Because of this rebound, it can be inferred that the patients did not show a durable increase in their potential for transplantation. The search for a more effective method to immunomodulate patients continues.
    Article · May 2013 · Clinical Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: The significance of donor-specific antibodies (DSA) is not well known in the setting of pancreas transplantation. Since December 2009, we prospectively followed pancreas transplant patients with single-antigen-luminex-bead testing at one, two, three, six, and then every six months for the first two yr. Thirty-five of the 92 patients that underwent pancreas transplantation (13 pancreas-alone [PTA], 20 with a kidney [SPK], and two after a kidney [PAK]) agreed to participate in study. Median age at transplant was 45 yr and follow-up was 23 months. Majority were Caucasian (n = 33) and male (n = 18). Rabbit anti-thymocyte globulin induction was used. Median HLA-mismatch was 4.2 ± 1.1. Eight patients (7SPK, 1PAK) developed post-transplant DSA at median follow-up of 76 d (26-119), 1 SPK had pre-formed DSA. Seven patients had both class I and class II DSA, one with class I and one with class II only. Mean peak class I DSA-MFI was 3529 (±1456); class II DSA-MFI was 5734 (±3204) whereas cumulative DSA MFI (CI + CII) was 9264 (±4233). No difference was observed in the patient and donor demographics among patients with and without DSA. One patient in non-DSA group developed acute cellular rejection of pancreas. From our data it appears that post-transplant DSA in pancreas allograft recipients may not impact the early-pancreatic allograft outcomes. The utility of prospective DSA monitoring in pancreatic transplant patients needs further evaluation and long-term follow-up.
    Article · Sep 2012 · Clinical Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: Kidney dysfunction is a recognized complication after non-renal solid organ transplantation, particularly after intestinal transplant. In our study, we reviewed data on 33 multivisceral transplant (MVT)- and 15 isolated small bowel (ISB)-transplant patients to determine risk factors for kidney dysfunction. Kidney function was estimated by modified diet in renal disease (MDRD) and Schwartz formula for adults and children, respectively. Acute kidney injury (AKI) was defined as an increase in the serum Cr (sCr) greater than twofold. Kidney function declined significantly at one yr after transplantation with 46% of subjects showing an estimated GFR (eGFR) <60 mL/min. Patients with an episode of AKI were more likely to have reduced eGFR than those without AKI (p < 0.025). In linear regression analyses, age, pre-transplant sCr, eGFR at postoperative day (POD) 30, 90, 180, 270, and tacrolimus level at POD 7 showed significant correlation with one yr post-transplant eGFR (p < 0.05). Pediatric patients and patients with MVT had lesser decline in kidney function compared with adults or patients with ISB. In conclusion, risk factors for post-transplant kidney dysfunction in intestinal transplantation included age, pre-transplant sCr, AKI episode, eGFR at POD 30, 90, 180, 270, and tacrolimus level at POD 7.
    Article · Jun 2012 · Clinical Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: More than half of the simultaneous pancreas kidney transplant (SPK) patients afflicted with BK virus nephropathy (BKVN) lose their kidney allograft. Fear of pancreatic rejection limits the ability to reduce immunosuppression; this may result in inadequate treatment of BKVN. This single-center retrospective review included 138 SPK patients who underwent periodic BKV screening and were managed with IS reduction alone as a treatment of choice for BKVN. All patients underwent rabbit anti-thymocyte globulin (rATG) induction and were maintained on tacrolimus/sirolimus or mycophenolate. The incidence of BKVN was 4.4%. BKVN was diagnosed at a median of 11 months; mean serum creatinine 2.1 mg/dL and the geometric mean BK serum viral load at diagnosis 1 758 000 DNA copies/mL. Median time to BKV clearance was 5.6 months; there was 96% reduction in the mycophenolate dose, 100% reduction in sirolimus, and 40% reduction in the tacrolimus blood level at BKVN clearance. No BKVN-related kidney failure was noted, and patients retained excellent kidney and pancreatic allograft function till last follow-up (43 months). BKVN in SPK is a potentially preventable cause of end-stage kidney disease, and IS reduction alone is an acceptable treatment modality in SPK without a higher risk of kidney/pancreas allograft loss as long as close monitoring can be ensured.
    Article · Mar 2012 · Clinical Transplantation
  • Article · Apr 2011 · American Journal of Kidney Diseases
  • [Show abstract] [Hide abstract] ABSTRACT: Kidney re-transplantation (KRT) candidates are considered at high risk for graft failure. Most of these patients are kept on a chronic steroid maintenance (CSM) regimen. The safety of early steroid withdrawal (ESW) remains unanswered in KRT. This study was aimed at comparing the outcomes of ESW and CSM in KRT. Retrospective analysis of 113 KRT patients (ESW, n=59; CSM, n=54) was performed. All patients received rabbit anti-thymocyte globulin/steroid induction and were maintained on mycophenolate/tacrolimus (±steroids). One- and 5-year patient survival for the ESW and the CSM group were not significantly different (98 versus 96% and 91 versus 88%, respectively; P=0.991). No significant difference was seen in the graft survival for both groups at 1 and 5 years (98 versus 93% and 80 versus 74%, respectively; P=0.779). Mean 1- and 5-year estimated GFR was not statistically different between the groups (P=0.773 and 0.790, respectively). The incidence of acute rejection at 1 year was 17 and 22% in ESW and CSM patients, respectively (P=0.635). Compared with the ESW group, patients in the CSM group were more likely to be hyperlipidemic (P=0.044), osteoporotic (P=0.010), post-transplant diabetics (P=0.051) and required more medications to control BP (P=0.004). ESW seems to be a reasonable approach in KRT recipients because the short and intermediate patient survival, graft survival, and graft function is comparable to CSM immunosuppression.
    Article · Nov 2010 · Clinical Journal of the American Society of Nephrology
  • [Show abstract] [Hide abstract] ABSTRACT: Mujtaba MA, Goggins W, Lobashevsky A, Sharfuddin AA, Yaqub MS, Mishler DP, Brahmi Z, Higgins N, Milgrom MM, Diez A, Taber T. The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients. Clin Transplant 2011: 25: E96–E102. © 2010 John Wiley & Sons A/S. Abstract: The aim of this study was to evaluate the utility of donor-specific antibodies (DSA) and flow cytometry crossmatch (FCCM) as tools for predicting antibody-mediated rejection (AMR) in desensitized kidney recipients. Sera from 44 patients with DSA at the time of transplant were reviewed. Strength of DSA was determined by single antigen Luminex bead assay and expressed as mean fluorescence intensity (MFI). T- and B-cell FCCM results were expressed as mean channel shift (MCS). AMR was diagnosed by C4d deposition on biopsy. Incidence of early AMR was 31%. Significant differences in the number of DSAs (p = 0.0002), cumulative median MFI in DSA class I (p = 0.0004), and total (class I + class II) DSA (p < 0.0001) were found in patients with and without AMR. No significant difference was seen in MCS of T and B FCCM (p = 0.095 and p = 0.307, respectively). The three-yr graft survival in desensitized patients with DSA having total MFI < 9500 was 100% compared to 76% with those having total MFI > 9500 (p = 0.022). Desensitized kidney transplant recipients having higher levels of class I and total DSA MFI are at high risk for AMR and poor graft survival. Recipient DSA MFI appears to be a more reliable predictor of AMR than MCS of FCCM.
    Article · Oct 2010 · Clinical Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: Indiana University's kidney transplant program has undergone changes in the program's approach to immunosuppression. This change in philosophy has moved the program away from multiple chronic maintenance immunosuppression strategies with corticosteroids to steroid-free maintenance immunosuppressive strategies for both adults and pediatric recipients. Anti-thymocyte globulin induction (beginning pre-reperfusion) has allowed for the rapid post-transplant withdrawal of corticosteroids. Steroid-free maintenance immunosuppression has been achieved with excellent patient and graft survival as well as lower rejection rates in the first posttransplant year. Desensitized recipients can also be safely included in steroid-free protocols. The administration of anti-thymocyte globulin prereperfusion combined with pulsatile perfusion storage of deceased donor kidneys has led to an extremely low delayed graft function rate.
    Article · Jan 2009 · Clinical transplants