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Objectives: Plasma cell-rich acute rejection is an aggressive form of acute rejection that occurs late after transplant and is usually resistant to standard antirejection therapy. This study reports the safety, efficacy, and outcomes of plasma cell-rich acute rejection after treatment with bortezomib, a proteasome inhibitor, in 10 patients after a first living-related renal transplant., Materials and Methods: Plasma cell-rich acute rejection was diagnosed using the 2007 Banff classification. The treatment protocol for plasma cell-rich acute rejection included methylprednisolone (500 mg/kg), 7 sessions of plasmapheresis, antithymocyte globulin (3-5 mg/kg/day for 10 days), rituximab (2 doses at 375 mg/m2), and bortezomib (1 cycle at 1.3 mg/m2)., Results: The mean age of recipients and donors was 23.70 ± 11.39 and 37.30 ± 12.82 years, respectively. The mean time to plasma cell-rich acute rejection was 3.1 ± 2.5 years. The mean serum creatinine level at rejection was 4.8 ± 2.7 mg/dL. After treatment, serum creatinine decreased to 3.3 ± 1.8 mg/dL. Serum creatinine levels at 1-year and 2-year follow-up were 3.0 ± 2.3 and 3.3 ± 0.9 mg/dL, respectively. There was 1 graft failure due to recurrence of glomerulonephritis/de novo glomerulonephritis. No significant adverse effects were noted in the patients. Bortezomib successfully reverted plasma cell-rich acute rejection and stabilized graft function, with patients showing 2-year graft survival after rejection of 90%., Conclusion: Bortezomib-based treatment was successful in reverting plasma cell-rich acute rejection and stabilizing graft function, with graft survival of 90% at 2 years. Further studies with large cohorts and randomized trials with or without bortezomib will help in better evaluation of its efficacy, safety, and outcomes.

Aim: Living donor kidney is the main source of donor organs in low to middle income countries. We aimed to develop a living donor risk model that predicts graft and patient survival in an emerging economy., Methods: We used data from the Sindh Institute of Urology and Transplantation (SIUT) database (n = 2283 recipients and n = 2283 living kidney donors, transplanted between 1993 and 2009) and conducted Cox proportional hazard analyses to develop a composite score that predicts graft and patient survivals., Results: Donor factors age, creatinine clearance, nephron dose (estimated by donor/recipient body weight ratio) and human leukocyte antigen (HLA) match were included in the living donor risk model. The adjusted hazard ratios (HRs) for graft failures among those who received a kidney with living donor scores (reference to donor score of zero) of 1, 2, 3 and 4 were 1.14 (95%CI: 0.94-1.39), 1.24 (95%CI:1.03-1.49), 1.25 (95%CI:1.03-1.51) and 1.36 (95%CI:1.08-1.72) (P-value for trend =0.05). Similar findings were observed for patient survival., Conclusions: Similar to findings in high income countries, our study suggests that donor characteristics such as age, nephron dose, creatinine clearance and HLA match are important factors that determine the long-term patient and graft survival in low income countries. However, other crucial but undefined factors may play a role in determining the overall risk of graft failure and mortality in living kidney donor transplant recipients., (© 2016 Asian Pacific Society of Nephrology.)

Objectives: Our aim was to analyze the immunohistopathologic features of plasma cell-rich acute rejection in a living-related renal transplant setting., Materials and Methods: Renal allograft biopsies of 50 cases of plasma cell-rich acute rejection were reviewed, and the main immunohistopathologic features were analyzed. The biopsies were studied using light microscopy, immunofluorescence, and immunohistochemistry and reported according to Banff classification. Biopsy findings were correlated with graft function and outcome., Results: From February 2012 to December 2013, 50/1630 (3%) dysfunctional renal allograft biopsies showed plasma cell-rich acute rejection. Among acute changes, interstitial inflammation was of moderate degree in 8 cases (16%) and severe in 42 cases (84%). Mild tubulitis was found in 4 cases (8%), moderate tubulitis in 8 cases (16%), and severe tubulitis in 38 cases (76%). Glomerulitis was found in 2 cases (4%). No presence of arteritis was found. All plasma cell-rich acute rejection cases were of tubulointerstitial type, and most were of type IB. The mean percent of plasma cells on light microscopy in all cases was 28.8 ± 11.7%, and the range was 10% to 60%, with 46 cases (92%) showing plasma cell percent of ≥ 20%. The mean plasma cell percent on immunohistochemistry for CD138 was 29.0 ± 12.4%. Microvascular inflammation was found in 34 cases (68%). C4d testing was done by immunofluorescence in 22 cases (44%) and was positive in 8 cases (36%). Interstitial fibrosis/tubular atrophy was mild in 18 (36%), moderate in 28 (56%), and severe in 4 cases (8%). Plasma cell enrichment did not correlate with a variety of clinical and pathologic features (all P > .05)., Conclusions: Plasma cell enrichment is not an independent prognostic morphologic feature and may represent either T-cell-mediated or antibody-mediated rejection or a mixture of these processes. Further investigations regarding its pathogenesis, accurate categorization, and treatment are needed.

Objectives: Our aim was to determine the clinical significance of borderline lymphocytic infiltrates on indicated renal allograft biopsies in a living related renal transplant setting., Materials and Methods: The study was conducted at the histopathology department of Sindh Institute of Urology and Transplantation. A retrospective review of 421 renal transplant patients was conducted from October 2007 to September 2008 to identify patients in whom a histologic diagnosis of borderline changes was made on dysfunctional renal allograft biopsies. Demographic, clinical, and laboratory data; biopsy findings; treatments given; and responses to treatment were collected and analyzed. Standard biopsy indications determined the need for graft biopsies. Biopsies were reported according to Banff criteria., Results: Mean age was 26.92 ± 9.14 years (range, 10-45) for recipients and 38.46 ± 9.16 years (range, 19-50) for donors. Males were predominant among recipients (84.6% vs 15.4%), and females were predominant among donors (57.7% vs 42.3%). The best serum creatinine levels were 1.79 ± 1.15 mg/dL (range, 0.83-6.12). These were achieved after a median of 3 days (interquartile range, 2-7.25). Dysfunctional biopsies exhibiting borderline infiltrates were performed at a median duration of 5.5 days (interquartile range, 3-14.25). Mean serum creatinine at the time of biopsy was 2.34 ± 1.43 mg/dL (range, 1.25-8.25). The biopsies showed borderline cellular infiltrates (interstitial inflammation 1 [i1] and tubulitis 1 and [t1] lesions). All recipients except one received antirejection treatment (antithymocyte globulin, n = 5; escalation of mycophenolate mofetil dosage, n = 1; pulse steroids, n = 19); all recipients responded with a decline in serum creatinine toward baseline, with a mean serum creatinine of 1.31 ± 0.42 mg/dL (range, 0.40-2.71). This response was achieved at a median duration of 9.73 ± 5.32 days (range, 1-23) after starting treatment., Conclusions: The borderline cellular infiltrates on dysfunctional renal allograft biopsies signify evolving phases of acute cellular rejection. These infiltrates responded favorably to antirejection treatment in our setting.

Kidney paired exchange is an established method of overcoming incompatibility in donor-recipient pairs and expanding the living-donor pool. It is infrequently performed in developing countries. We report the first kidney paired exchange in Pakistan, successfully performed at our center. One donor-recipient pair consisted of a 38-year-old female recipient (blood type, B positive) and her 40-year-old husband (A positive) as the potential donor. The second pair consisted of a 30-year-old male recipient (A positive) and his 30-year-old wife (B positive) as the potential donor. The donors were exchanged with the recipients, and both pairs were antigen matched for human leukocyte antigen A and human leukocyte antigen DR. Luminex antibody screening was negative, as were the crossmatches for T and B cells and for IgG and IgM. The transplant procedures and recoveries proceeded uneventfully. The recipients are maintaining serum creatinine levels around 0.78 mg/dL and 0.90 mg/dL, 1 year after transplant. Kidney paired exchange is a relatively low-cost option for overcoming the barrier of incompatibility in a resource-constrained setting.

Background: Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcomes., Patients and Methods: Between February 2012 and December 2013, 1630 dysfunctional renal graft biopsies were performed. Of these, 50 (3%) showed PCAR. ARs with >10% plasma cells were defined as PCAR. Human leukocyte antigen (HLA) antibodies were tested in historic sera and at the time of PCAR. Treatment for PCAR comprised methylprednisolone, antithymocyte globulin, plasmapheresis, and anti-CD20 antibody., Results: Of the 1630 dysfunctional biopsies, 50 (3%) had PCAR which occurred 3.1 ± 2.55 yr after transplant. The percentage of plasma cells was 28.8 ± 11.7, and CD138, 29.0 ± 12.4. Donor-specific antibodies (DSAs) were found in 32 (64%) overall, Class I in 15% and Class II in 65%. Post-treatment serum creatinine improved from 3.80 ± 2.59 to 2.66 ± 1.59 mg/dL in DSA positive (p < 0.003) and from 2.59 ± 1.09 to 2.08 ± 0.86 mg/dL in DSA negative (p < 0.008). One- and two-yr graft survival after PCAR was 72%, 42% in the DSA-positive vs. 89%, 82% in the DSA-negative group, respectively (p = 0.071)., Conclusions: Our results show that PCAR occurs late after transplant and in many cases is associated with DSAs. Graft outcome was poor when PCAR was associated with DSAs., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)