A better understanding of the immunobiological processes and predictors of graft rejection holds promise for the development of potential therapeutic strategies and also individualization of immunosuppression. The objective of this study is to analyze the clinical relevance of immune parameters such as antidonor antihuman leukocyte antigen (anti-HLA) antibodies, monitoring of cytokines and their receptors on the graft outcome following live-related donor renal transplantation. Flow cytometry-based methods were used to detect antidonor antibodies (flow cytometry crossmatch, FCXM) and intracellular cytokines. Enzyme-linked immunosorbent assay (ELISA) methods were employed to detect anti-HLA class I and class II antibodies and quantitative serum-soluble interleukin-2 receptor (sIL-2R) levels. The data revealed that patients with HLA class I-specific IgG antibody experienced higher acute rejection (AR) episodes at 1 yr in comparison to the antibody negative group (82% vs. 56%, p = 0.01). On the contrary, donor-specific class II antibodies (B+) did not have any influence on the graft survival. However, 15 recipients having both T- and B-cell antidonor antibodies (T+B+) had significantly poor graft survival (60%) as compared to the antibody-negative group (T-B-, 82%, p = 0.05). Additionally, patients having non-donor but HLA-specific antibodies (FCXM-/ELISA+) had poor graft survival as compared to the antibody-negative group (64% vs. 88%, p < 0.05). Further, patients undergoing AR episodes had significantly higher expression of IFN-gamma-producing T cells (19.16 +/- 7.4% median 17.50) as compared to their pre-transplant levels (5.68 +/- 1.63%, Median 5.20) and the non-rejecter group (5.97 +/- 4.39%, median 4.3, p = 0.0004). Similarly sIL-2 was significantly increased in AR episodes during the first month of transplantation (292 +/- 131.5 pmol/L) as compared to those with well-functioning grafts (p = 0.01) and healthy controls (p = 0.001). Evaluation of antidonor antibodies by flow cytometry is found to be relatively more sensitive and a better predictor of graft outcome. Further monitoring of cytokine expression profile of primed peripheral T-helper cells and quantitative analysis of sIL-2R offer additional valuable diagnostic and prognostic tools for follow-up of transplant subjects and a better alternative for functional assessment of immunosuppression.

Antibodies↗

PubMedDate not supplied

Prospective randomized control trial of isoniazid chemoprophylaxis during renal replacement therapy.

BACKGROUND: Infectious diseases remain among the major morbid events in patients with end-stage renal disease (ESRD) on renal replacement therapy (RRT). In developing countries, tuberculosis (TB) has been found to occur more frequently in these patients than in the general population. Efficacy of isoniazid (INH) chemoprophylaxis has been seen in other situations, such as human immunodeficiency virus infection. However, studies on INH prophylaxis in ESRD patients on RRT are limited. METHODS: In this prospective randomized controlled trial, from April 2000 to June 2001, a total of 109 ESRD patients registered for renal transplant and accepted for maintenance hemodialysis in our hospital were included and followed up until June 2004 to assess the role of INH prophylaxis in preventing development of TB. At the time of acceptance for hemodialysis, 54 patients were assigned to receive daily INH for 1 year and 55 patients were assigned to the control group. Primary outcome was development of TB. Secondary outcome was INH hepatotoxicity. To evaluate the effect of INH prophylaxis on the development of TB, a Kaplan-Meier survival estimate was used to plot TB-free survival curve and log-rank test was used for comparison. RESULTS: Overall, TB was diagnosed in 27 patients during RRT, with an incidence of 24.8%. TB developed in 9 (16.7%) patients in the INH group and in 18 (32.7%) patients in the control group. There was a significantly lower incidence of TB in the INH group as compared with the control group. The risk ratio of INH vs. control group for development of TB was 0.40 (95% confidence index [CI], 0.17-0.92; P=0.032). In the INH group 27 (50%) patients and in the control group 17 (30.9%) patients developed some hepatic dysfunction. However, significant hepatitis that required discontinuation of INH developed in only 9 (16.7%) patients in the INH group. Furthermore, significant hepatitis also developed in 6 (10.9%) patients in the control group. The majority of patients with significant hepatitis in both groups (INH as well as control) were subsequently found to be positive for hepatitis B and/or hepatitis C viral infection. Mild hepatitis (which did not require discontinuation of INH) was seen in 18 (33.3%) patients in the INH group and 11 (20%) patients in the control group. Viral hepatitis infection was not found in any of the milder cases of hepatitis in either group. CONCLUSION: This study shows significant efficacy of INH chemoprophylaxis during RRT in preventing development of TB, when the INH was started during dialysis itself. INH chemoprophylaxis was safe and well tolerated in the majority of patients. However, mild hepatic dysfunction was common, both in the treatment as well as in the control group. As the incidence of viral hepatitis overall was high in our patients on RRT, it is difficult to identify INH-induced hepatitis in this clinical setting.

Adolescent↗

PubMedDate not supplied

Pulmonary mucormycosis in a diabetic renal transplant patient.

A 50-year-old male, diabetic, post transplant patient had recurrent pneumonia. The first episode responded well to antibiotics, while on the second occasion he had a necrotising pneumonia, which developed into a thick-walled cavity. Despite antibiotics, his condition rapidly deteriorated precluding bronchoscopy or percutaneous biopsy. Post-mortem lung biopsy revealed typical hyphae of mucormycosis.

Biopsy, Needle↗

PubMedDate not supplied

The first successful simultaneous pancreas-kidney transplant in India.

Insulin-dependent diabetes mellitus is associated with renal failure, diabetic retinopathy, neuropathy and vasculopathy. We report the first successful simultaneous pancreas-kidney transplant in India in a young diabetic with renal failure. The dual transplant has cured his diabetes and renal failure and has had a beneficial effect on his neuropathy, retinopathy and quality of life. Obstacles to dual transplant in India include a lack of suitable recipients and a cadaver donor programme that is still in its infancy.

Adult↗