Publications by authors named "Simin Goral"

39 Publications

Use of Point-of-Care Ultrasound to Assess CKD.

Am J Kidney Dis 2021 01;77(1):A16-A19

Penn Medicine, Philadelphia, PA.

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http://dx.doi.org/10.1053/j.ajkd.2020.06.021DOI Listing
January 2021

Current state of kidney transplantation in patients with HIV, hepatitis C, and hepatitis B infection.

Clin Transplant 2020 10 29;34(10):e14048. Epub 2020 Aug 29.

Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common chronic viral infections in the end-stage kidney disease (ESKD) patient population that were once considered relative contraindications to kidney transplantation. In this review, we will summarize the current state of kidney transplantation in patients with HIV, HCV, and HBV, which is rapidly evolving. HIV+ patients enjoy excellent outcomes in the modern transplant era and may have new transplant opportunities with the use of HIV+ donors. Direct-acting antivirals for HCV have substantially changed the landscape of care for patients with HCV infection. HBV+ patients now have excellent patient and allograft survival with HBV therapy. Currently, kidney transplantation is a safe and appropriate treatment for the majority of ESKD patients with HIV, HCV, and HBV.
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http://dx.doi.org/10.1111/ctr.14048DOI Listing
October 2020

Lupus Nephritis and Kidney Transplantation: Where Are We Today?

Adv Chronic Kidney Dis 2019 09;26(5):313-322

Renal-Electrolyte and Hypertension Division, University of Pennsylvania Medical Center, Philadelphia, PA. Electronic address:

Lupus nephritis (LN) is the cause of end-stage kidney disease (ESKD) for 1.9% of the ESKD population in the United States. Although the incidence rates of ESKD from LN stopped rising in recent years, racial disparities in waiting time, pre-emptive kidney transplant, and transplant outcomes still exist. Patients with LN who progress to ESKD tend to be female, of African ancestry, and young. Kidney transplantation is safe in this population and associated with a substantial survival benefit, primarily due to reduced deaths from cardiovascular disease and infection. Transplant outcomes for patients with ESKD due to LN are similar to those without LN.
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http://dx.doi.org/10.1053/j.ackd.2019.08.007DOI Listing
September 2019

Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Transpl Int 2019 Dec 8;32(12):1268-1276. Epub 2019 Oct 8.

Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.
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http://dx.doi.org/10.1111/tri.13520DOI Listing
December 2019

Bariatric surgery before and after kidney transplantation: long-term weight loss and allograft outcomes.

Surg Obes Relat Dis 2019 Jun;15(6):935-941

Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Background: Severe obesity is frequently a barrier to kidney transplantation, and kidney transplant recipients often have significant weight gain following transplantation.

Objectives: The goals of this study were to evaluate the long-term risks and benefits of bariatric surgery before and after kidney transplantation.

Setting: University Hospital, United States.

Methods: We performed a retrospective cohort study of 43 patients who had pretransplantation bariatric surgery and 21 patients who had posttransplantation bariatric surgery from 1994 to 2017 with propensity-score matching to identify matched controls using national registry data.

Results: Body mass index at the time of transplantation was similar in patients who underwent bariatric surgery before versus after transplantation (32 versus 34 kg/m, P = .172). There was no significant difference in body mass index in the 5 years after bariatric surgery among patients who underwent bariatric surgery before versus after kidney transplantation (36 versus 32 kg/m, P = 0.814). Compared with matched controls, bariatric surgery before (n = 38) and after (n = 18) kidney transplantation was associated with a decreased risk of allograft failure (hazard ratio .31 [95% confidence interval .29-0.33] and .85 [95% confidence interval .85-.86] for pre- and posttransplant, respectively) and mortality (hazard ratio .57 [95% confidence interval .53-.61] and .80 [95% confidence interval .79-.82] for pre- and posttransplant, respectively).

Conclusions: Bariatric surgery before and after kidney transplantation results in similar maintenance of weight loss and improved long-term allograft survival compared with matched controls. Bariatric surgery appears to be a safe and reasonable approach to weight loss both before and after transplantation.
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http://dx.doi.org/10.1016/j.soard.2019.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690384PMC
June 2019

Single-center, real-world experience with granulocyte colony-stimulating factor for management of leukopenia following kidney transplantation.

Clin Transplant 2019 06 11;33(6):e13541. Epub 2019 Apr 11.

Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Leukopenia is a frequent complication following kidney transplantation. Granulocyte colony-stimulating factor (G-CSF) has been used to accelerate white blood cell (WBC) count recovery; however, published experience in kidney transplantation is limited.

Methods: We retrospectively reviewed our kidney transplant recipients from January 2012 to September 2016 with a G-CSF order to evaluate leukopenia management (defined as WBC <3000 cells/μL).

Results: Thirty-six recipients were included. On average, G-CSF treatment began at 98 ± 38 days. At G-CSF initiation, mean WBC count was 1240 ± 420 cells/μL and absolute neutrophil count (ANC) was 653 ± 368 cells/μL. Mean G-CSF dose was 4.6 ± 1.2 mcg/kg/dose (total 11.8 ± 9.0 mcg/kg), 77.8% of recipients were prescribed G-CSF as outpatients, and overall, median time to WBC count recovery was 9 (IQR 4-14) days. Changes in immunosuppression and prophylaxis regimens for leukopenia were also common. Within 1 month following leukopenia onset, no patients experienced acute rejection and 5 (14%) developed infection requiring hospitalization or opportunistic infection.

Conclusion: In kidney recipients with leukopenia, G-CSF may be helpful to achieve WBC count recovery in addition to changes in immunosuppression and prophylaxis medications. Prospective, randomized data are still needed to determine optimal G-CSF dosing in this population.
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http://dx.doi.org/10.1111/ctr.13541DOI Listing
June 2019

Safety and Feasibility of Outpatient Rabbit Antithymocyte Globulin Induction Therapy Administration in Kidney Transplant Recipients.

Pharmacotherapy 2018 06;38(6):620-627

Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Kidney transplant induction therapy often includes inpatient administration of rabbit antithymocyte globulin (rATG) over multiple days. To reduce hospital length of stay (LOS) and drug expenditures, the rATG induction course was completed in the outpatient setting via peripheral intravenous administration. The present study assesses early readmission trends ascribable to an outpatient rATG administration protocol to ensure initial reduction in hospital LOS is sustained early after discharge.

Methods: This was a retrospective study of kidney recipient outcomes for patients transplanted between January 1, 2008, and February 29, 2016, immediately following implementation of an outpatient rATG protocol. Readmission data within 7 days of outpatient rATG administration were collected. The relatedness of rATG administration to an adverse drug reaction resulting in readmission was determined by the World Health Organization-Uppsala Monitoring Centre Causality Assessment Scale and the Naranjo Adverse Drug Reaction Probability Scale.

Results: A total of 1104 patients received outpatient doses of rATG and were included. An upward trend in kidney transplant volume and outpatient rATG administrations per year was found from 2008-2015. Following protocol implementation, the percentage of overall readmissions ranged from 9% to just over 12% from 2008-2014 and remained less than 10% for 2014 through 2016. The percentage of outpatient rATG infusions that potentially led to rATG-related readmissions was less than 4% per year over the study period. A total of 1124 hospital days were saved, 125 days per year on average.

Conclusions: Outpatient administration of rATG is feasible, safe, and did not increase readmissions in the period directly following administration. The findings of this analysis support our continued use of the outpatient rATG protocol at our institution.
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http://dx.doi.org/10.1002/phar.2116DOI Listing
June 2018

Adherence rates to ferric citrate as compared to active control in patients with end stage kidney disease on dialysis.

Hemodial Int 2017 04 12;21(2):243-249. Epub 2016 Sep 12.

University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Introduction: Oral phosphate binders are the main stay of treatment of hyperphosphatemia. Adherence rates to ferric citrate, a recently approved phosphate binder, are unknown.

Methods: We conducted a post-hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease (ESKD) who were randomized to ferric citrate vs. active control (sevelamer carbonate and/or calcium acetate). Adherence was defined as percent of actual number of pills taken to total number of pills prescribed.

Findings: There were no significant differences in baseline characteristics including gender, race/ethnicity, and age between the ferric citrate and active control groups. Baseline phosphorus, calcium, and parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and 81.7% (15.9) in the ferric citrate and active control groups, respectively (P = 0.88). Adherence remained similar between both groups after adjusting for gender, race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean [95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder. Subjects with CVD had lower adherence rates to phosphate binder; this was significant only in the active control group.

Discussion: Adherence rates to the phosphate binder, ferric citrate, were similar to adherence rates to active control. Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label. Gender, race/ethnicity, nor age influenced adherence.
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http://dx.doi.org/10.1111/hdi.12487DOI Listing
April 2017

Kidney transplantation due to medical urgency: time for reconsideration?

Nephrol Dial Transplant 2016 09 24;31(9):1376-7. Epub 2016 Mar 24.

Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

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http://dx.doi.org/10.1093/ndt/gfw035DOI Listing
September 2016

The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial.

Am J Kidney Dis 2015 Sep 7;66(3):479-88. Epub 2015 May 7.

Tufts Medical Center, Boston, MA.

Background: Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels.

Study Design: 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment.

Setting & Participants: Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders.

Intervention: 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate).

Outcomes: Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year.

Measurements: Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate.

Results: There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25 mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95 mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1 pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control.

Limitations: Open-label study, few peritoneal dialysis patients.

Conclusions: Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.
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http://dx.doi.org/10.1053/j.ajkd.2015.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868355PMC
September 2015

Transplant nephrectomy: histologic findings—a single center study.

Am J Nephrol 2014 9;40(5):491-8. Epub 2014 Dec 9.

Hospital of the University of Pennsylvania, Department of Medicine, Renal, Electrolyte, and Hypertension Division, Philadelphia, Pa., USA.

Aims: To identify the histopathological features of transplant nephrectomy (TN) specimens.

Methods: We performed retrospective analysis of 73 nephrectomies to review the histopathology in detail and correlate the Banff grading characteristics of TN specimens with time post engraftment and clinical features. Retrospective data on donor-specific antibodies (DSA) were also collected.

Results: The majority of patients who had TN in less than 3 months posttransplant (n = 20; median time to TN: 4 days) had hemorrhagic infarction; 7 patients (35%) had grade 3 acute rejection (AR). Patients who had TN later than 3 months posttransplant (n = 53; median time to TN: 67 months) had AR, grade 2B (21%) and 3 (43%), coexisting with advanced vascular injury in the form of interstitial hemorrhage, extensive interstitial fibrosis and tubular atrophy (IF/TA) as well as the presence of DSAs. Overall, the majority of patients without DSA pre-TN developed DSA post-TN.

Conclusions: Our data revealed extensive inflammation and ongoing immunologic activity in a subset of patients with a failed graft. Careful and individualized approach based on clinical and laboratory data should guide the decision for transplant nephrectomy.
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http://dx.doi.org/10.1159/000369865DOI Listing
August 2015

Persistent BK viremia does not increase intermediate-term graft loss but is associated with de novo donor-specific antibodies.

J Am Soc Nephrol 2015 Apr 25;26(4):966-75. Epub 2014 Sep 25.

Department of Medicine, Renal Electrolyte and Hypertension Division.

There are limited data regarding intermediate-term outcomes in patients with persistent BK viremia. Other viral infections have been implicated in the development of allosensitization through heterologous immunity, but the relationship between BK viremia and donor-specific antibodies (DSAs) is unexplored. In 2008, we initiated routine post-transplant BK viremia and DSA screening at our center; 785 kidney or kidney-pancreas transplant recipients were included in our study. Of these recipients, 132 (17%) recipients developed BK viremia during the study period. The median duration of BK viremia was 140 days (interquartile range=40-393 days), and persistent BK viremia was defined as lasting ≥140 days. Kaplan-Meier curves were generated to assess differences in patient and allograft survival on the basis of BK viremia status; survival was modeled using Cox proportional hazard regression. After a median follow-up of 3 years, there was no significant difference in terms of patient (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.28 to 2.49) or allograft survival (HR, 0.80; 95% CI, 0.37 to 1.73) between patients with and without BK viremia, which was confirmed in a time-varying analysis. In our logistic regression model, persistent BK viremia was strongly associated with the development of class II (HR, 2.55; 95% CI, 1.30 to 4.98) but not class I (HR, 1.13; 95% CI, 0.46 to 2.77) DSAs. These data suggest that persistent BK viremia does not negatively affect intermediate-term patient or allograft survival but is associated with increased risk for de novo DSA, although the exact mechanism is unclear.
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http://dx.doi.org/10.1681/ASN.2014010119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378106PMC
April 2015

BK virus infection: an update on diagnosis and treatment.

Nephrol Dial Transplant 2015 Feb 25;30(2):209-17. Epub 2014 Feb 25.

Renal, Electrolyte, and Hypertension Division, University of Pennsylvania Medical Center, Philadelphia, PA, USA.

BK virus, first isolated in 1971, is a significant risk factor for renal transplant dysfunction and allograft loss. Unfortunately, treatment options for BK virus infection are limited, and there is no effective prophylaxis. Although overimmunosuppression remains the primary risk factor for BK infection after transplantation, male gender, older recipient age, prior rejection episodes, degree of human leukocyte antigen mismatching, prolonged cold ischemia time, BK serostatus and ureteral stent placement have all been implicated as risk factors. Routine screening for BK has been shown to be effective in preventing allograft loss in patients with BK viruria or viremia. Reduction of immunosuppression remains the mainstay of BK nephropathy treatment and is the best studied intervention. Laboratory-based methods such as ELISPOT assays have provided new insights into the immune response to BK and may help guide therapy in the future. In this review, we will discuss the epidemiology of BK virus infection, screening strategies, treatment options and future research directions.
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http://dx.doi.org/10.1093/ndt/gfu023DOI Listing
February 2015

Plasmacytic post-transplant lymphoproliferative disorder: a case series of nine patients.

Transpl Int 2013 Jun 28;26(6):616-22. Epub 2013 Mar 28.

Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. Although PTLD typically has a B-cell histology, an uncommon variant, plasmacytic PTLD can present as a monoclonal plasma cell proliferation similar to plasmacytomas seen in multiple myeloma. A retrospective analysis was performed on nine patients at our center with plasmacytic PTLD as characterized by plasmacytic histology with the presence of CD138 and lack of CD20. Of the 210 adult solid organ transplant PTLD patients diagnosed between 1988 and 2012, 9 (4%) had a histological appearance consistent with plasmacytic PTLD. The median time from transplant to diagnosis was 3.7 years (range 8 months-24 years). All patients presented with extranodal and often subcutaneous solid tumors. Laboratory features included elevated LDH and beta-2 microglobulin levels, monoclonal gammopathy, and EBV positivity of the tumor. Unlike conventional multiple myeloma, patients had normal calcium levels and only mild anemia. Six patients who have completed treatment achieved complete responses with radiation therapy and/or reduction in immunosuppression with two patients now greater than 5 years in continuous complete response. Plasmacytic PTLD, despite its plasmacytic histology, is responsive to conventional therapies used for B-cell PTLD including reduction in immunosuppression and radiation therapy.
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http://dx.doi.org/10.1111/tri.12091DOI Listing
June 2013

Elevated serum creatinine in a kidney transplant recipient: unusual suspect.

Clin Nephrol 2012 Oct;78(4):322-4

Department of Medicine, Renal, Electrolyte, and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.

We report a rare form of transplant renal artery stenosis discovered 3 months after transplantation. Our patient had mechanical renal artery "kinking", which responded to balloon angioplasty. Doppler ultrasound, followed by an arteriogram confirmed the diagnosis. This case demonstrates that transplant renal artery "kinking" stenosis,though rare, can cause graft dysfunction and worsening hypertension in kidney transplant recipients.
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http://dx.doi.org/10.5414/cn107121DOI Listing
October 2012

Efficacy and safety of extended-duration inpatient-to-outpatient rabbit antithymocyte globulin induction in de novo kidney transplant recipients: 6-month outcomes.

Transplantation 2012 Sep;94(5):506-12

Department of Pharmacy Services, Hospital of University of Pennsylvania, Philadelphia, PA 19104-4322, USA.

Background: In an effort to reduce length of stay (LOS) in kidney transplant recipients otherwise ready for discharge, we developed a protocol to extend rabbit antithymocyte globulin (rATG) induction therapy into the outpatient setting through peripheral dose administration.

Methods: A retrospective review of outpatient rATG group (n=185) that received the first two rATG doses inpatient and subsequent doses outpatient was used, compared with concurrently transplanted patients who received all doses of rATG as an inpatient (n=99).

Results: The outpatient group received more rATG (cumulative mg/kg induction) than the inpatient-only group (median [range], 4.8 mg/kg [3.2-10.0] vs. 4.4 mg/kg [2.8-8.6]; P<0.01). Outpatient usage avoided 246 hospital days that would have been required had rATG been administered in the inpatient setting. The incidences of perioperative leukopenia and thrombocytopenia were lower in the outpatient rATG group versus inpatient-only group (5% vs. 21%, P<0.01, and 2% vs. 9%, P<0.01, respectively) but were similar by 3 months. The outpatient rATG group experienced shorter hospitalization LOS compared with the inpatient-only group (median LOS [range], 4 [2-11] vs. 5 [3-20] days; P<0.01) and lower 30-day readmission rates (30% vs. 42%, P=0.03). At 6 months, there were no differences in incidences of biopsy-proven rejection episodes.

Conclusions: When implemented selectively among less complicated kidney transplant recipients, delayed extension of rATG into the outpatient setting was associated with LOS reduction and attendant cost saving without either increasing readmission rate or compromising short-term safety and efficacy.
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http://dx.doi.org/10.1097/TP.0b013e31825c58c0DOI Listing
September 2012

Changes in vitamin D binding protein and vitamin D concentrations associated with liver transplantation.

Liver Int 2012 Feb 9;32(2):287-96. Epub 2011 Sep 9.

Renal Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6021, USA.

Background: Vitamin D deficiency is associated with fractures, infections and death. Liver disease impairs vitamin D and vitamin D binding protein (DBP) metabolism.

Aims: We aimed to determine the impact of liver transplantation on vitamin D, particularly on DBP and free vitamin D concentrations.

Methods: Serum 25(OH)D, 1,25(OH)(2) D and DBP concentrations were measured in 202 adults before liver transplantation and 3 months later in 155. Free vitamin D concentrations were estimated from these values. Risk factors for 25(OH)D deficiency (<20 ng/ml) and low 1,25(OH)(2) D (<20 pg/ml) were examined with logistic regression, and changes in concentrations following transplantation with linear regression.

Results: Pretransplant, 84% were 25(OH)D deficient, 13% had 25(OH)D concentrations <2.5 ng/ml, and 77% had low 1,25(OH)(2) D. Model for end-stage liver disease score ≥ 20 (P < 0.005) and hypoalbuminemia (P < 0.005) were associated with low 25(OH)D and 1,25(OH)(2) D concentrations. Following transplantation, 25(OH)D concentrations increased a median of 17.8 ng/ml (P < 0.001). Albumin increased from a median of 2.7 to 3.8 g/dl (P < 0.001) and DBP from 8.6 to 23.8 mg/dl (P < 0.001). Changes in total 25(OH)D were positively and independently associated with changes in DBP (P < 0.05) and albumin (P < 0.001). Free 25(OH)D concentrations rose from 6.0 to 9.7 pg/ml (P < 0.001). In contrast, total 1,25(OH)(2)D concentrations rose only by 4.3 pg/ml (P < 0.001) and free 1,25(OH)(2D concentrations declined (P < 0.001).

Conclusions: Serum total and free 25(OH)D and DBP concentrations rose substantially following transplantation, while 1,25(OH)(2) D concentrations showed modest changes and free 1,25(OH)(2) D decreased. Studies of the effects of vitamin D status on diverse transplant complications are needed.
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http://dx.doi.org/10.1111/j.1478-3231.2011.02638.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566950PMC
February 2012

The influence of induction therapy for kidney transplantation after a non-renal transplant.

Clin J Am Soc Nephrol 2012 Jan 10;7(1):158-66. Epub 2011 Nov 10.

Division of Transplantation, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background And Objectives: Non-renal transplant recipients who subsequently develop ESRD and undergo kidney transplantation are medically and immunologically complex due to comorbidities, high cumulative exposure to immunosuppressants, and sensitization to alloantigen from the prior transplant. Although prior non-renal transplant recipients are one of the fastest growing segments of the kidney wait list, minimal data exist to guide the use of antibody induction therapy (IT+) at the time of kidney after lung (KALu), heart (KAH), and liver (KALi) transplant.

Design, Setting, Participants, & Measurements: This retrospective cohort study used national registry data to examine IT use and survival after kidney transplantation. Separate multivariate Cox regression models were constructed to assess patient survival for IT+ and IT- KALu (n=232), KAH (n=588), and KALi (n=736) recipients.

Results: Use of IT increased during the study period. The percentage of patients considered highly sensitized (panel reactive antibody ≥20%) was not statistically significant between IT+ and IT- groups. IT+ was not associated with improvement in 1- and 10-year patient survival for KALu (P=0.20 and P=0.22, respectively) or for KAH (P=0.90 and P=0.14, respectively). However, IT+ among KALi was associated with inferior patient survival at 1 and 10 years (P=0.04 and P=0.02, respectively).

Conclusions: Use of IT for kidney transplantation among prior non-renal transplant recipients may not offer a survival advantage in KALu or KAH. However, due to limited power, these findings should be interpreted cautiously. IT+ was associated with inferior outcomes for KALi. Use of IT should be judicially reconsidered in this complex group of recipients.
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http://dx.doi.org/10.2215/CJN.02360311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265339PMC
January 2012

Age, exclusion criteria, and generalizability of randomized trials enrolling kidney transplant recipients.

Transplantation 2011 Apr;91(8):858-63

Department of Medicine, Renal Division, University of Pennsylvania, Philadelphia, PA 19104-6021, USA.

Background: The proportion of elderly (≥65 years) kidney transplant recipients (KTRs) doubled in the United States from 1999 to 2008. Given higher mortality, more medication side effects, and less rejection among elderly KTRs, optimal care of these patients may require tailored decisions about transplant therapeutics. It is unknown whether participants in transplant clinical trials-which generate the best evidence for patient care-are representative of the aging population of KTRs.

Methods: Using PubMed, we identified randomized trials involving KTRs from 1999 to 2008 and determined age-exclusion criteria and the mean age of participants. The mean age of these trial participants was compared with the mean age of the overall population of incident KTRs in the United States.

Results: The 87,222 participants in 573 trials were significantly younger than the US KTR population (P<0.05). This age discrepancy worsened over the study period (during the years 2006 to 2008, the mean age was 45 years for trial participants versus 50 years for US KTRs, P<0.05). Thirty percent of trials had an exclusion criterion based on older age, and 16% excluded recipients aged 65 years or older. In multivariable regression, immunosuppression trials (P<0.01) and trials in higher impact journals (P=0.03) were more likely to exclude the elderly, but there was no significant difference in exclusion of elderly patients based on a trial's geographic location.

Conclusions: Trial participants are younger than KTRs in the United States and many trials exclude older patients. Transplant investigators should make strong efforts to recruit patients across the total age spectrum.
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http://dx.doi.org/10.1097/TP.0b013e31820f42d9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462443PMC
April 2011

Kidney transplantation in patients with a prior heart transplant.

Transplantation 2010 Feb;89(4):427-33

Division of Transplant Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA.

Background: Chronic kidney disease among prior heart transplant recipients is a growing problem that is likely to place an increased demand on a limited supply of kidney allografts. Allocation of the limited resource of kidneys for transplantation requires consideration of the demands of fair distribution and optimizing patient and graft survival. The aim of this study was to compare the kidney transplant outcomes among recipients of kidney after prior heart transplantation (KAH, n=456) with kidney transplantation in other clinical settings.

Methods: A retrospective cohort study using United Network for Organ Sharing registry data (1995-2008) was performed comparing renal allograft survival among KAH recipients with patients who underwent simultaneous kidney-heart transplant (SKH, n=252), primary kidney transplant alone (KA1, n=112,882), or repeat kidney transplant alone (KA2, n=14,070).

Results: The annual number of KAH recipients more than quadrupled during the study period from 24 in 1995 to 99 in 2008. In a multivariable analysis using Cox regression, allograft survival among KAH recipients was not different from SKH (P=0.16, hazards ratio [HR]=0.79, confidence interval [CI]=0.57-1.10), and KA2 (P=0.11, HR=0.86, CI=0.72-1.04), but it was inferior to KA1 (P<0.001, HR=0.66, CI=0.55-0.80). Patient death accounted for 75.2% of KAH kidney loss. Kidney quality as measured by living or deceased donors (P=0.62) and standard criteria or extended criteria (P=0.87) was not associated with survival; however, there was a trend toward improved survival (P=0.08) among recipients of a preemptive transplant.

Conclusion: Kidney graft survival among prior heart transplant recipients is inferior to KA1 but similar to other clinical scenarios. Preemptive transplantation with an extended criteria or living donor kidney should be encouraged.
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http://dx.doi.org/10.1097/TP.0b013e3181c42248DOI Listing
February 2010

Aortic calcification predicts cardiovascular events and all-cause mortality in renal transplantation.

Nephrol Dial Transplant 2009 Apr 22;24(4):1314-9. Epub 2009 Jan 22.

Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Background: Cardiovascular disease is a leading cause of death among renal transplant recipients. Aortic calcification is associated with increased mortality in dialysis subjects. The significance of aortic calcification among renal transplant recipients is unknown. Our objective was to prospectively examine the association of aortic calcification with cardiovascular events and all-cause mortality among asymptomatic incident renal transplant recipients.

Methods: One hundred and twelve renal transplant recipients underwent electron beam computed tomography. Aortic calcification was scored by the Agatston method. The mean follow-up time was 5.1 years. Cardiovascular events (heart failure, coronary artery disease, peripheral arterial disease and stroke) and all-cause mortality were recorded.

Results: The cohort consisted of 62% Caucasians, 38% African Americans and 62% male gender. The mean age was 49.0 +/- 12.5 years. Thirty-four percent had aortic calcification. During follow-up, 12 cardiovascular events and 10 deaths were recorded. Subjects with aortic calcification had more cardiovascular events compared to those without aortic calcification (23.7 versus 4.1%, P = 0.001). Recipients with aortic calcification had higher mortality compared to those without aortic calcification but it did not reach statistical significance (15.8 versus 5.4%, P = 0.07). The univariate hazard ratio of aortic calcification score in a proportional hazard Cox model to assess event-free survival was 1.15 (1.04-1.27, P = 0.01). Diabetes and aortic calcification score were independently associated with survival. In addition to the predictors above, dialysis vintage was an independent predictor for combined future cardiovascular event and mortality.

Conclusions: In conclusion, aortic calcification is prevalent among renal transplant recipients and is predictive of future cardiovascular events. Aortic calcification is easily identified by non-invasive testing, and should be considered when assessing cardiovascular risk in asymptomatic renal transplant recipients.
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http://dx.doi.org/10.1093/ndt/gfn753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721431PMC
April 2009

Kidney transplantation at the University of Pennsylvania: 1998-2008.

Clin Transpl 2009 :143-52

University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Kidney transplantation at the University of Pennsylvania has grown substantially over the past 11 years. Although our transplant volume has increased primarily as a consequence of multiorgan transplants as well as the utilization of historically "marginal" allografts, our post-transplantation outcomes remain excellent in both children and adults. We attribute these outcomes to technical improvements in tissue typing and donor-recipient crossmatching, modification of immunosuppression protocols, and rigorous donor and recipient selection. In the next decade, we hope to substantially expand our living donor program and refine our overall donor and recipient selection process such that we maintain excellent post-transplant outcomes in the face of aging and increasingly comorbid donors and recipients. We further predict significant changes in post-transplant management of kidney recipients with respect to immunosuppression regimens. In particular, we anticipate the modulation of immunosuppression regimens in recipients with high titers of donor-specific antibody and the integration of B-cell specific immunosuppression into post-transplant patient care. Only time will tell whether such therapies will 1) improve long-term outcomes, 2) allow us to diminish the degree of non-specific pharmacologic immunosuppression currently in use, 3) or even promote donor-specific tolerance in kidney transplant recipients.
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July 2010

Experience with antibody-mediated rejection in kidney allograft recipients.

Clin Transpl 2006 :439-46

Department of Pharmacy, Kidney Transplantation Program, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

In our case series, AMR occurred in patients who had DSA. Twelve of the 21 patients (57%) who developed de novo antibodies post-transplant had biopsy-proven episodes of either rejection (of any Banff classification) and/or chronic allograft nephropathy. Only one-third of these 12 patients with rejection episodes were classified as AMR. It is unclear when and how often measurements for DSA should be performed after transplantation. When AMR is suspected, the detection of anti-HLA antibodies should be done using very sensitive assays. An increase in PRA and/or the detection of anti-HLA antibodies specific to previous sensitization events may precede an episode of AMR, even in the absence of DSA. Prospective clinical trials are needed to assess the predictive value of the presence of DSA after transplant. It is uncertain which therapeutic response should follow after the detection of these antibody responses in the absence of clinical symptoms. AMR requires intensive therapy, but no standard treatment has been established. Three patients who had AMR at our center were treated with rituximab in addition to various combinations of plasmapheresis, methylprednisolone, OKT3, and intravenous immune globulin. Only one patient responded to this treatment. Well-controlled clinical trials would help to evaluate the efficacy and benefit of B-cell depletion in combination with other immunosuppressive agents.
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May 2008

Preformed donor-directed anti-HLA-DP antibodies may be an impediment to successful kidney transplantation.

Nephrol Dial Transplant 2008 Jan 23;23(1):390-2. Epub 2007 Oct 23.

Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.

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http://dx.doi.org/10.1093/ndt/gfm703DOI Listing
January 2008

Rapidly reversible cardiogenic shock as a pheochromocytoma presentation.

Am J Med 2007 Sep;120(9):e1-2

Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

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http://dx.doi.org/10.1016/j.amjmed.2006.08.031DOI Listing
September 2007

Posttransplantation anemia at 12 months in kidney recipients treated with mycophenolate mofetil: risk factors and implications for mortality.

J Am Soc Nephrol 2006 Nov 11;17(11):3240-7. Epub 2006 Oct 11.

Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6144, USA.

Although posttransplantation anemia (PTA) is common in the mycophenolate mofetil era, its impact on patient survival is unknown. This retrospective cohort study characterized factors that are associated with PTA 12 mo after transplantation in mycophenolate mofetil-treated kidney recipients and explored whether 12-mo PTA affects outcomes. The records of 626 kidney recipients were examined for presence of anemia (hemoglobin <12 g/dl). Multivariate regression models, fit with covariates that had unadjusted relationships, investigated both risk factors for 12-mo PTA and whether 12-mo PTA contributes to mortality. Anemia prevalence was 72, 40, and 20.3% at 1, 3, and 12 mo, respectively. By multivariate logistic regression, anemia at 3 mo (odds ratio [OR] 10.0; 95% confidence interval [CI] 5.3 to 17.1; P = 0.0001), donor age (OR 1.0; 95% CI 1.1 to 1.3; P = 0.005), and 3-mo creatinine (OR 2.0; 95% CI 1.2 to 3.3; P = 0.044) were associated with 12-mo PTA. The PTA cohort had inferior patient survival (P = 0.02, log rank) and a higher proportion of cardiovascular deaths (6.3 versus 2.2%; P = 0.017) than nonanemic patients. By Cox regression, 12-mo PTA (hazard ratio [HR] 3.0; 95% CI 1.3 to 6.7; P = 0.009), 12-mo creatinine (HR 1.3; 95% CI 1.1 to 1.4; P = 0.008), age at transplantation (HR 1.1; 95% CI 1.1 to 1.2; P = 0.004), and hepatitis C seropositivity (HR 2.8; 95% CI 1.1 to 7.0; P = 0.03) were associated with mortality. There was no interaction between 12-mo PTA and serum creatinine. In conclusion, 12-mo PTA is associated with an increased risk for patient death. The presence of anemia 3 mo after kidney transplantation is a major determinant of 12-mo PTA. PTA in kidney recipients therefore should be defined by its persistence or occurrence beyond the third posttransplantation month.
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http://dx.doi.org/10.1681/ASN.2006010027DOI Listing
November 2006

Recurrence of lupus nephritis after renal transplantation: if we look for it, will we find it?

Nat Clin Pract Nephrol 2005 Dec;1(2):62-3

Saint Barnabas Medical Center in Livingston, NJ, USA.

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http://dx.doi.org/10.1038/ncpneph0028DOI Listing
December 2005

24-week oral ganciclovir prophylaxis in kidney recipients is associated with reduced symptomatic cytomegalovirus disease compared to a 12-week course.

Transplantation 2006 Apr;81(8):1106-11

Division of Renal-Electrolyte and Hypertension, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Background: Cytomegalovirus (CMV) infection is associated with reduced graft and patient survival among kidney recipients. The highest risk of CMV infection occurs in CMV-naive recipients of kidneys from seropositive donors (D+/R-). Optimal CMV prophylaxis is not established. This prospective cohort study compared the safety and efficacy of prophylaxis with 12 versus 24 weeks of oral ganciclovir.

Methods: We prospectively administered 24 weeks ganciclovir to 31 D+/R- recipients. The control group comprised 39 patients transplanted in the immediately preceding era who received a 12-week course of prophylaxis. All patients received cytolytic therapy within the first month, as well as a tacrolimus-based maintenance regimen. A logistic regression model was fit to examine the relationship between 24 weeks ganciclovir prophylaxis and the odds of developing CMV infection by one year.

Results: Groups were matched, though the 12-week cohort had more delayed graft function than their 24-week counterparts (45% vs. 29%, P=0.04). CMV infection occurred in 31% and 7% patients in the 12-week and 24-week groups, respectively (P
Conclusions: Oral ganciclovir prophylaxis for 24 weeks is associated with a lower risk of symptomatic CMV disease than a 12-week course in high risk D+/R- kidney recipients.
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http://dx.doi.org/10.1097/01.tp.0000204048.90367.97DOI Listing
April 2006

Macroscopic hematuria in a kidney transplant recipient: a rare cause.

Am J Kidney Dis 2006 Jan;47(1):e3-7

Division of Renal, Electrolytes and Hypertension, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-0812, USA.

Pseudoaneurysm formation in a renal transplant is an uncommon complication of such interventional procedures as percutaneous nephrostomy or renal biopsy; symptoms may be delayed for days or even years. Presentation may vary from incidental discovery to worsening renal insufficiency to life-threatening hemorrhage. We report a case of macroscopic hematuria from a pseudoaneurysm that developed in a kidney transplant recipient after placement of a percutaneous nephrostomy tube. This patient was treated with transcatheter embolization, which is highly effective. A high index of suspicion, along with early diagnosis and transcatheter embolization, are essential for the management of hematuria caused by pseudoaneurysm formation from percutaneous nephrostomy tube placement.
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http://dx.doi.org/10.1053/j.ajkd.2005.09.016DOI Listing
January 2006

Complications related to dapsone use for Pneumocystis jirovecii pneumonia prophylaxis in solid organ transplant recipients.

Am J Transplant 2005 Nov;5(11):2791-5

Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

Dapsone, used for prevention of Pneumocystis jirovecii infections, has been reported to cause hemolytic anemia and methemoglobinemia; its tolerability in solid organ transplant recipients is not well described. We investigated dapsone-related adverse events in patients undergoing solid organ transplantation from 1999 to 2004. Transplant providers identified patients for the investigators who then reviewed the patients' hospital and outpatient records. Sixteen solid organ transplant recipients fit case definitions for dapsone-related hemolytic anemia (n = 11) or methemoglobinemia (n = 5). Median time from event to dapsone discontinuation was 15 days; all patients improved after drug discontinuation. G6PD enzyme activity was normal in all patients whose test results were available. Dapsone may be associated with hemolytic anemia or methemoglobinemia, even with normal G6PD levels. These events are often not promptly recognized, and drug discontinuation is delayed. Dapsone-related hemolytic anemia or methemoglobinemia should be considered in solid organ transplant recipients with unexplained anemia or hypoxia.
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http://dx.doi.org/10.1111/j.1600-6143.2005.01079.xDOI Listing
November 2005