Management of Plasma Cell-Rich Acute Rejection in Living-Related Kidney Transplant: Role of Proteasome Inhibitor.

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.

Adrenal myelolipoma: a report of three cases and review of literature.

Adrenal myelolipoma is a rare and benign tumour composed of mature adipose tissue and haematopoietic elements that resemble bone marrow. It is mostly discovered incidentally on imaging of abdomen done for non adrenal related reasons or at autopsy. Usually asymptomatic, but has been reported to present with symptoms such as flank pain resulting from tumour bulk, necrosis or spontaneous retroperitoneal haemorrhage. Symptomatic tumours, growing tumours or tumours larger than 10 cm should be excised surgically. We report cases of 3 male patients presenting with flank pain and upper pole renal masses. All three were treated surgically with adrenalectomy. Myelolipoma was confirmed in all three on histology.

Prognostic factors of survival in patients with non-resectable hepatocellular carcinoma: hepatitis C versus miscellaneous etiology.

OBJECTIVE: To identify prognostic determinants of survival in patients with non-resectable hepatocellular carcinoma (HCC), determine the effect of transarterial chemoembolization (TACE) on prognosis, compare hepatitis C related HCC with mixed etiologies and evaluate the prognostic value of different staging systems. METHODS: This cohort study included 129 patients (male = 97, 75%) with non-resectable HCC. Data was collected from 2002 until August 2006. A series of demographic, clinical and biochemical and radiological data were collected. Cases were staged according to the Child's, Okuda, Cancer Liver Italian program (CLIP), Barcelona Clinic Liver Cancer (BCLC) and Chinese University Prognostic Index (CUPI) systems. Survival analysis was performed. Any effect of TACE on prognosis was recorded. RESULTS: Median age of patients was 52 years (range 18-82). Median follow-up 11 months (range 2-36). At the time of analysis, 102 patients had died (79%). Etiology of HCC was hepatitis C virus (HCV) in 66 (51.2%), hepatitis B virus (HBV) 31 (24%), HBV + HCV 10 (7.8%), HBV + delta hepatitis 02 (1.6), and non-B non-C 20 (15.4%). Forty-one patients (31%) were offered TACE. Univariate analysis for HCV related HCC showed that age > 52 years (p<0.05), bilirubin >1.17 mg/dl (p<0.01), INR > 1.3 (p<0.01), alpha fetoprotein > 400 ng/ml (p<0.05), splenomegaly (p<0.01), ascites (p<0.001), portal vein thrombosis (p<0.01), splenic varices (p<0.01), and TACE not offered (p<0.01) were the prognostic factors while in miscellaneous etiology female sex (p<0.05), haemoglobin < 11.0 gm/dl (p<0.01), alkaline Phosphatase > 169 lU/L (p<0.05), ascites (p<0.05) and multifocality (p<0.05) were adversely effecting prognosis. Overall independent determinants were Hepatitis C etiology, female sex and multifocality of tumour (Hazard ratios 3.0, 3.0 and 1.9 respectively). Mean survival was 17.2 vs. 12.8 months for patients offered vs. not offered TACE respectively (p value = 0.015). Okuda, CLIP, BCLC, CUPI and Child's staging systems retained their performance as judged by chi square values in regression analysis. Discriminatory ability for death evaluated by receiver operating characteristic curve was better for Okuda system in the first year. CONCLUSION: Hepatitis C as the etiology of HCC, female sex and multi-focality are associated with poor prognosis. HCV related HCC may differ in prognostic factors from non-HCV HCC. Simple staging system by Okuda predicts prognosis effectively in non-resectable.

Cryoglobulinaemia and autoimmune markers in hepatitis C virus infected patients on renal replacement therapy.

OBJECTIVE: To investigate the association of cryoglobulinaemia and autoimmune markers with hepatitis C virus (HCV) infection in patients on maintenance haemodialysis (HD) and post renal transplantation. METHODS: Serum samples of 103 HCV-antibody (anti-HCV) positive and 105 anti-HCV negative patients were investigated for cryoglobulins. These comprised 136 patients on HD and 72 renal transplant recipients. Serum creatinine and liver function tests were obtained on all patients. Rheumatoid factor (RF), anti nuclear antibodies (ANA), anti smooth muscle antibodies (ASMA), liver kidney microsomal antibodies (LKM), immunoglobulins (Igs) and complement levels were performed on all cryoglobulin positive (cryopositive) samples. HCV RNA and genotyping detection tests were done for cryopositive patients. RESULTS: The prevalence of cryoglobulins in patients on HD or after renal transplantation was found to be higher (57.6%) among anti-HCV positive patients compared to the anti-HCV negative patients (42.4%) (P=0.000). RF, ANA and ASMA were also higher in cryopositive HCV infected patients. HCV RNA was present in 84.2% of anti-HCV positive patients. Cryoprecipitable RF activity was found in a higher number of symptomatic patients with HCV genotype 1 compared to HCV genotype 3. CONCLUSION: There is an association of cryoglobulinaemia and autoimmune markers in HCV infected patients on HD, and in HCV positive renal transplant recipients. Also HCV genotype 1 is associated with symptomatic mixed cryoglobulinaemia.

Cyclosporine induced nephrotoxicity in renal transplant recipients: clinical significance of fractional excretion of sodium, potassium and magnesium.

OBJECTIVE: Evaluation of fractional excretion of Sodium, Potassium and Magnesium as indicators of cyclosporine (CsA) toxicity in de-novo renal transplant recipients. METHODS: A prospective study was conducted on 59 live related renal allograft recipients. Fractional excretion(FE) of sodium (Na+), potassium (K+) and magnesium (Mg2+) were calculated on day 1, 3, 5 and 10 post transplant. Graft dysfunctions were evaluated by colour-Doppler, CsA levels and renal biopsy. Normal ranges were determined on 30 healthy subjects. RESULTS: The mean creatinine on day 1 was 3.1 +/- 1.3 mg/dl and declined to 1.6 +/- 1.2 on day 10. FE of Na+, K+ and Mg2+ were 12 +/- 9%, 34 +/- 20% and 13 +/- 10% respectively on day 1 and reduced to 2.2 +/- 2%, 11 +/- 14% and 11 +/- 14% on day 10. Of the 59 recipients, 38 (64%) had uneventful recovery (group A), 21(36%) had graft dysfunction [6 acute rejection (group B) and 15 either acute tubular necrosis or high CsA(group C)]. In group A, on day 1, FENa+, FEK+ and FEMg2+ were 5 +/- 4%, 24 +/- 12% and 6.6 +/- 3% respectively and these declined to 1.2 +/- 0.6%, 4.6 +/- 0.7% and 6 +/- 3% respectively on day 10. Compared to group A, group C had significantly high values on day 1, FENa+ 15 +/- 8%, FEK+ 36 +/- 24% and FEMg2+ 21 +/- 10% (p < 0.0001) and on day 10, FENa+ 3.7 +/- 2.7%, FEK+ 20 +/- 15% and FEMg2+ 15 +/- 8% (p < 0.05). In the group B, day 1 and day 10 levels were FENa+ 6 +/- 3%, FEK+ 26 +/- 13% and FEMg2+ 7 +/- 2.8% and FENa+ 1.2 +/- 0.7%, FEK+ 4.2 +/- 0.5%, FEMg2+ 7 +/- 4% respectively. CsA levels and AUC did not correlate with CsA toxicity. CONCLUSION: FE of magnesium is a useful marker of CsA toxicity independent of CsA blood levels. FE studies can supplement renal biopsy findings.