Muhammad A. Mujtaba

The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.

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.

Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

Background Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. Methods In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%–99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti–human leukocyte antigen antibodies were analyzed before and after desensitization. Results Reduction of cPRA from 25% to 50% was noted for anti–class I (5 patients, within 20–60 days) and anti–class II (3 patients, within 10–20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti–class I antibodies at 350 days and anti–class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti–class II antibodies, and history of previous transplant. Conclusions The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

Vascular catastrophes following pancreas transplantation: an evolution in strategy at a single center.

Fridell JA, Johnson MS, Goggins WC, Beduschi T, Mujtaba MA, Goble ML, Powelson JA. Vascular catastrophes following pancreas transplantation: an evolution in strategy at a single center. 
Clin Transplant 2012: 26: 164–172. 
© 2011 John Wiley & Sons A/S.

Risk factors for native kidney dysfunction in patients with abdominal multivisceral/small bowel transplantation

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.

BK virus nephropathy in simultaneous pancreas kidney transplant: A potentially preventable cause of kidney allograft loss

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.

Pancreas transplantation after bariatric surgery

Porubsky M, Powelson JA, Selzer DJ, Mujtaba MA, Taber T, Carnes KL, Fridell JA. Pancreas transplantation after bariatric surgery. 
Clin Transplant 2012: 26: E1–E6. 
© 2011 John Wiley & Sons A/S.

Correlation between CT-based measured renal volumes and nuclear-renography-based split renal function in living kidney donors. Clinical diagnostic utility and practice patterns

Living 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 (SRF) as measured by nuclear renography in potential living donors and its impact on kidney selection decision.

Impact of tacrolimus-sirolimus maintenance immunosuppression on proteinuria and kidney function in pancreas transplant alone recipients

Background Nephrotoxicity is a major complication with immunosuppression regimens used in transplantation. Calcineurin inhibitor–sparing or reduction regimens using sirolimus (SRL) have shown variable success in kidney transplantation. There is limited data on the role of SRL on native kidney function in pancreas transplantation. Methods All patients undergoing pancreas transplantation from 2003 to 2010 were enrolled in this study (n=65). Patient demographic characteristics were identified and divided into two groups: those receiving tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and those maintained on a regimen of Tac and SRL with or without MMF. The slopes for estimated glomerular filtration rate (eGFR), serum creatinine level (sCr), and proteinuria changes over time were assessed between groups. Urine protein and creatinine ratio (uPr/uCr) was used to assess proteinuria. Results There was no difference in baseline demographic characteristics. Patients were followed for a median of 3 years. Baseline sCr and eGFR were similar between groups. Differences in uPr/uCr and rate of change in sCr and eGFR were not significant between the groups overall or for any specific time. There was worsening of sCr, eGFR, and uPr/uCr within the groups over the period of study. There were no significant differences when groups were split by age or gender or when the SRL group was split further based on MMF inclusion. Conclusions Our study findings suggest that using a Tac-SRL regimen in patients with pancreas alone transplantation is a safe approach and may not lead to worsening proteinuria and kidney function when compared with regimens using Tac with MMF.

Effective ionic dialysance/blood flow rate ratio: an indicator of access recirculation in arteriovenous fistulae.

Effective ionic dialysance (EID) is an online measure of hemodialysis (HD) effective urea clearance that is calculated using changes in dialysate sodium conductivity. Effective ionic dialysance is blood flow (Qb) dependent. The presence of significant (≥5%) access recirculation (sAR) during dialysis lowers EID at a given Qb, thereby lowering EID/Qb. We propose using EID/Qb as a useful chairside tool for detection of sAR in arteriovenous fistulae (AVF). Data were collected from 47 patients with AVF (72% men, mean age 49 ± 11.8 years, duration on dialysis 3.78 ± 3.4 years, duration of fistula use 3.35 ± 3.42 years) dialyzed with an high-efficiency dialyzer with a mass transfer area coefficient (KoA) of 1714 ml/min. Effective ionic dialysance were measured at regular intervals by the Gambro Phoenix dialysis system during treatments. The access recirculation (AR) and access blood flow (Qa) were measured using the reference standard saline dilution technique (Transonic HD-02 monitor). Among the 323 HD sessions where Qb, EID, AR, and Qa were available, we identified 17 instances of sAR. The performance of EID/Qb as indicator of sAR was assessed by a receiver operator characteristic (ROC) curve (Stata version 10.1). The area under the ROC curve was 0.935 (95% confidence interval 0.869–1.000), which demonstrated a sensitivity of 76.5% and specificity of 96.4% at an EID/Qb ≤50% with a positive likelihood ratio of 21, negative likelihood ratio of 0.24, positive predictive value of 54.2%, and negative predictive value of 98.7%. We found similar test performance in patients who received HD with dialyzers with smaller surface areas and lower KoAs. The high specificity of EID/Qb makes it an excellent yet simple and early chairside indicator of AVF recirculation.

Early findings of prospective anti-HLA donor specific antibodies monitoring study in pancreas transplantation: Indiana University Health Experience

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.