Layla Kamal

Safety and Efficacy of Treatment of Hepatitis C in Kidney Transplant Recipients with Directly Acting Antiviral Agents.

Background With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited data exists on its safety and efficacy. Methods We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function. Results A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332–6254). Conclusions Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.

Pretransplant immunologic risk assessment of kidney transplant recipients with donor-specific anti-human leukocyte antigen antibodies.

Background Patients with pretransplantation strong donor-specific anti–human leukocyte antigen (HLA) antibodies (DSA) are at higher risk for rejection. We aimed to study the safety of kidney transplantation in patients with lower strength DSAs in a prospective cohort study. Methods Three hundred and seventy-three consecutive adult kidney transplant recipients with (DSA+; n=66) and without (DSA−; n=307) DSA were evaluated. Anti-HLA antibodies with mean fluorescence intensity values over 5,000 for HLA-A, HLA-B, and HLA-DR and more than 10,000 for HLA-DQ were reported as unacceptable antigens. Patients received transplant if flow cytometry T-cell and B-cell cross-match channel shift values were less than 150 and 250, respectively, with antithymocyte globulin and intravenous immunoglobulin induction treatment. Results Patients had a mean number of 1.6±0.8 DSAs with a mean fluorescence intensity value of 2,815±2,550. Twenty-seven percent were flow cytometry cross-match positive with T-cell and B-cell channel shift values of 129±49 and 159±52, respectively. During a median follow-up of 24 months (range, 6–50), there were no statistically significant differences in patient (99% vs. 95%) and graft survival (88% vs. 90%) rates between DSA+ and DSA− groups, respectively. Cumulative acute rejection rates of 11% in the DSA+ group and 12% in the DSA− group were similar. Two DSA+ (3%) and five DSA− (2%) patients developed chronic antibody-mediated rejection (3%). The mean serum creatinine levels were identical between the two groups (1.4±0.6 mg/dL). Conclusion Similar patient and graft survival, and acute rejection rates can be achieved in DSA+ patients compared to DSA− patients with pretransplantation immunologic risk assessment.

Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies.

The diagnostic criteria for antibody-mediated rejection (AMR) are continuously evolving. Here we investigated the clinical and molecular significance of different Banff microvascular inflammation (MVI) scores in transplant kidney biopsies. A total of 356 patients with clinically indicated kidney transplant biopsies were classified into three groups based on MVI scores of 0, 1, 2, or more for Groups 1-3, respectively. Gene expression profiles were assessed using arrays on a representative subset of 93 patients. The incidence of donor-specific anti-HLA antibodies was increased from 25% in Group 1 to 36% in Group 2 and to 54% in Group 3. Acute and chronic AMR were significantly more frequent in Group 3 (15% and 35%) compared with the Group 2 (3% and 15%) and Group 1 (0% and 5%), respectively. Gene expression profiles showed increased interferon-γ and rejection-induced, cytotoxic and regulatory T-cell, natural killer cell-associated and donor-specific antibody (DSA)-selective transcripts in Group 3 compared with Groups 1 and 2. There was no significant difference in gene expression profiles between the Groups 1 and 2. Increased intragraft expression of DSA-selective transcripts was found in the biopsies of C4d- Group 3 patients. Thus, an MVI score of 2 or more was significantly associated with a histological diagnosis of acute and chronic antibody-mediated rejection. Hence, increased intragraft DSA-selective gene transcripts may be used as molecular markers for AMR, especially in C4d- biopsies.

Clinical, Histological, and Molecular Markers Associated With Allograft Loss in Transplant Glomerulopathy Patients.

Background We aimed to investigate the clinical, histopathological, and molecular factors associated with allograft loss in transplant glomerulopathy (TGP) patients. Methods Of the 525 patients who underwent clinically indicated kidney biopsies, 52 (10%) had diagnosis of TGP. Gene expression profiles of 28 TGP and 11 normal transplant kidney biopsy samples were analyzed by Affymetrix HuGene 1.0 ST expression arrays. Results Over a median follow up of 23 months (1-46 months) after the diagnosis of TGP by biopsy, 17 patients (32%) lost their allografts at a median of 16 months (1-44 months). There was no difference between the 2 groups in terms of any demographic variables, serum creatinine, panel reactive antibody levels, donor-specific antibody frequency, or mean fluorescence intensity values. Patients who lost their allograft had a significantly higher median spot protein to creatinine ratio 2.81 (1.20-6.00) compared to no graft loss patients 1.16 (0.15-2.53), (P < 0.01), and a trends toward a higher mean chronic glomerulopathy (cg) score (1.65 ± 0.93 vs 1.11 ± 0.93) (P = 0.05). There was also no difference in microvascular inflammation or any other Banff injury scores between the 2 groups. Although 117 gene transcripts were upregulated in both groups, 86 and 57 were upregulated in graft loss and functioning allograft groups, respectively. There were significantly increased levels of intragraft endothelial cell–associated transcripts, gene transcripts associated with complement cascade, interleukins and their receptors and granulysin in graft loss patients compared to patients with a functioning allograft. Conclusion Our results demonstrate differential intragraft gene expression profiles in TGP patients with allograft loss.

Increased access to transplantation of highly sensitized patients under the new kidney allocation system. A single center experience

We aimed to investigate the impact of the new kidney allocation system (KAS) on the rate of transplantation of sensitized patients at our center. Pre-KAS and post-KAS intervals were Jan 1st to Dec 3rd 2014 and Jan 1st 2015 to Dec 3rd 2015, respectively. The number of deceased-donor crossmatches performed by flow cytometry increased from 715 pre-KAS to 1188 post-KAS. The percent of crossmatches performed for sensitized patients with calculated panel reactive antibody (cPRA)>0% increased from 19% pre-KAS to 26% post-KAS (p<0.0001). The number of deceased-donor kidney transplants performed at our center increased from 115 pre-KAS to 125 post-KAS (9% increase). There was a significant increase in the percentage of deceased-donor kidney transplants received by sensitized candidates (from 14% to 26% pre- and post-KAS, respectively; p<0.0001). The highest increase was seen in the patients with cPRA>98%, from 0% to 9%, followed by the group with cPRA 50-79%, from 5% to 8%. This increase was balanced by a decrease of 12% in the percentage of non-sensitized recipients, and a modest decrease of 1% in the group with cPRA 1-49%. In conclusion, transplant rate has increased in sensitized patients after KAS. The highest increase was observed among highly sensitized patients (cPRA>98%).

Pregnancy in sensitized kidney transplant recipients: a single-center experience

We aimed to examine the clinical outcomes of sensitized pregnant kidney transplant recipients.

Outcomes of Kidney Transplant Recipients From Donation After Circulatory Death Donors Without Preagonal Heparin Administration.

Machine Perfusion Terminal Resistive Index <0.2 mm Hg/mL per min 41.7 52.2 0.46 0.21-0.35 mm Hg/mL per min 41.7 43.5 >0.35 mm Hg/mL per min 16.7 4.4 Recipient, Black race 51.7 56.5 0.21 Recipient, Female 51.7 30.4 0.16 Recipient age, y 54.3 ± 16.3 55.4 ±. 10.1 0.78 Recipient, diabetes mellitus 44.8 56.5 0.58 Previous solid organ transplant 10.3 0 0.25 Thymoglobulin induction 55.2 30.4 0.10 Panel-reactive antibody > 0 27.6 4.4 0.03 Human leukocyte antigen mismatch > 4 58.6 34.8 0.10

Kidney transplantation in patients with severe preoperative hypertension

Severe systemic hypertension (HTN) is a risk factor for perioperative cardiovascular complications; however, its impact at the time of kidney transplantation (KTX) is not well defined.

Kidney transplant complications from undiagnosed benign prostatic hypertrophy

It is estimated that approximately 50% of males over 50 have benign prostatic hypertrophy (BPH). BPH is underappreciated in anuric patients with end stage renal disease, and failure of diagnosis in this population can lead to complications after kidney transplantation.

Improving pancreas graft utilization through importation

We analyze our outcomes utilizing imported allografts as a strategy to shorten wait list time for pancreas transplantation.