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Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by rapid progression to end-stage renal disease (ESRD). We evaluated the clinicopathological spectrum of cFSGS and compared its clinical behavior to steroid and tacrolimus (TAC)-resistant noncollapsing focal segmental glomerulosclerosis (FSGS). All patients (>14 years) diagnosed with cFSGS were enrolled in the study. Staining for differentiated podocyte markers such as WT 1, PAX and KI67 were performed in all patients. The outcome and histological features of cFSGS was compared with a prospectively followed cohort of steroid and TAC-resistant noncollapsing FSGS. The study included 22 cFSGS patients and 19 cases of steroid and TAC-resistant FSGS. Complete remission, partial remission, steroid resistance, progression to ESRD and death were observed in 13.6%, 4.5%, 27.3%, 36.4% and 18.2% patients, respectively. Patients with cFSGS had higher serum creatinine and more advanced tubulointerstitial changes compared to resistant FSGS. Twenty-six percent of therapy resistant noncollapsing FSGS progressed to ESRD after two years of stopping TAC. However, there was no difference in progression to ESRD between cFSGS and therapy-resistant noncollapsing FSGS at the end of two years. Glomerular collapse in the setting of FSGS is poorly responsive to treatment and has a high rate of progression to ESRD. The long-term prognosis of cFSGS and steroid and TAC-resistant FSGS are similar.

We studied tear flow in 23 renal transplant patients receiving cyclosporine A. Four minute Schirmer test was done once before and three times after starting cyclosporine A. Average tear flow was 9.7+/-0.9 before treatment and 15.9+/-1.1 at 1-2 months after renal transplant, 16.5+/-1.3 at 3-5 months and 17.6+/-1.4 at 8-10 months. Tear flow was significantly increased following oral cyclosporine treatment.

Introduction: Renal transplantation and immunosuppression are associated with an increased incidence of malignancy. Reduction or cessation of immunosuppressive therapy has been advocated in these cases to prevent tumor progression and recurrence. We evaluated the outcome of treatment of oropharyngeal cancer (OC) after renal transplantation without cessation of immunosuppressive therapy., Methods: The database of patients with OC after renal transplantation was analyzed with respect to age, sex, type of immunosuppression, interval between transplantation and diagnosis of cancer, as well as method of treatment and survival., Results: Thirty one (2.06%) renal transplant recipients developed malignancy including 6 (20%) with OC. Lingual cancer was seen in three, and one each showed an isolated tonsillar lymphoma, a parotid carcinoma, or a carcinoma of the larynx with only the last having had two other malignancies in the past. Three subjects were on immunosuppression with azathioprine and prednisolone, and the others were prescribed cyclosporine and prednisolone. Average time from transplantation to diagnosis of OC was 106 months. The interval was the shortest (2 years) for tonsillar lymphoma in an 18-year-old patient who received cyclosporine and showed features of left follicular tonsillitis. The patient with advanced carcinoma of the larynx did not receive any treatment and succumbed within 3 months. The dose of cyclosporine was reduced in the lymphoma case but immunosuppression was not altered in the other patients. All subjects were treated with a standard protocol. During a mean follow-up of 33 months, one had local recurrence of parotid carcinoma and the others showed well functioning renal grafts., Conclusion: Comprehensive treatment of OC after renal transplantation without withdrawing the immunosuppression prolonged the life of these patients with functioning grafts.

High treatment costs force the discontinuation of cyclosporine (CSA) in a vast majority of renal transplant recipients in India. The impact of CSA withdrawal among 108 living related renal transplant recipients 12.54 +/- 4.2 months after transplantation was studied retrospectively. In 83 patients, CSA was withdrawn over a 12-week period (group I). Azathioprine dosage was increased to 2 to 2.5 mg/kg/d, and prednisolone, to 30 mg/d 2 weeks and 1 week before starting CSA withdrawal, respectively. In the other 25 patients, CSA had to be withdrawn faster (mean, 28.52 +/- 14.18 days; group II). Twenty-nine rejection episodes (26.9%) were noted in 22 patients (20.4%; 19% in group I and 52% in group II; P: = 0.008). Fifteen group-I patients (18%) and 11 group-II patients (44%) died or lost their grafts (P: = 0.017). There was no difference in age, donor source, HLA matches, pretransplantation cross-match positivity, delayed graft function, immunosuppressive drug doses, rejection episodes, or prewithdrawal serum creatinine levels between the patients who did or did not develop acute rejection after CSA withdrawal. On follow-up, 10 patients (50%) died or returned to dialysis among the rejection group compared with 16 patients (18%) in the nonrejection group (P: = 0.007). The mean creatinine level at last follow-up was greater in the rejection group (3.97 +/- 2.54 versus 1.65 +/- 1.1 mg/dL; P: < 0.001). CSA withdrawal because of economic constraints carries a significant risk for acute rejection and death and/or graft loss in Indian living donor renal transplant recipients, even after 12 months.

Transplant recipients are predisposed to develop opportunistic infections such as tuberculosis, and isoniazid (INH) is used in most antitubercular therapeutic and prophylactic protocols. Cyclosporine (CyA) bioavailability increases with the concomitant use of drugs that inhibit hepatic cytochrome P-450 enzymes. There are conflicting reports on a possible interaction between the two drugs. Seven renal transplant recipients on CyA (Sandimmun Neoral) with slow acetylation status and also requiring concomitant INH prophylaxis (300 mg/day) against tuberculosis were studied. There were no significant changes in CyA pharmacokinetic parameters including CyA trough levels, total CyA exposure and CyA clearance before and 2 weeks after instituting INH prophylaxis. There was also no statistically significant correlation between INH levels and changes in CyA pharmacokinetic parameters before and after administration of INH. Even after all post-INH pharmacokinetic parameters were adjusted for INH levels, the differences in the above pre- and post-INH parameters did not reach statistical significance. Renal function during the study period remained constant and there were no episodes of CyA toxicity or acute rejection during and up to 4 weeks of INH treatment. We conclude that concomitant administration of INH and CyA is safe and is not associated with any appreciable alterations in the bioavailability of CyA.

Background: Cyclosporin (CsA) is metabolized primarily in the liver by cytochrome P-450 enzymes. Concomitant use of fluconazole can increase CsA concentrations by inhibiting this enzyme system and the effect seems to be dose dependent, with no interaction noted when fluconazole is used in a dose of 100 mg/day. Two previous investigations studying this interaction while using higher doses of fluconazole have provided inconsistent results. Recommendations advising an empirical 50% CsA dosage reduction in these patients have not been tested in a prospective trial., Methods: We studied six renal transplant recipients on CsA immunosuppression in a prospective, unblinded, crossover trial. Baseline renal functions, CsA area under the curve (AUC), Cmax, Cmin, CsA clearance, and Tmax were compared with those 2, 4 and 7 days after starting fluconazole orally in a dose of 200 mg/day. From day 8 onwards, patients reduced CsA dose by 50% and the above parameters were repeated on day 14., Results: CsA AUC increased from 2887 +/- 1729 ng.h/ml on day 0 to 3842 +/- 1975 ng.h/ml on day 2 (P < 0.05), 4750 +/- 1718 ng.h/ml on day 4 (P< 0.01) and then decreased to 4052 +/- 1687 ng.h/ml on day 7 (P<0.01). Following CsA dose reduction by 50%, the mean AUC decreased significantly to 2330 +/- 1602 ng x h/ml (P<0.01). The Cmax showed a significant increase from 701 +/- 345 ng/ml on day 0 to 941 +/- 326 ng/ml (P < 0.01) on day 4 but decreased from 768 +/- 292 ng/ml on day 7 to 498 +/- 289 ng/ml on day 14, P<0.01. The mean Cmin increased from 207 +/- 138 ng/ml on day 0 to 274 +/- 168 ng/ml on day 4. No significant changes were observed in CsA clearance and Tmax. On repeated-measurement ANOVA, only the AUC and Cmax on day 4 of fluconazole were significantly higher than day 0 (P<0.001). There was a large interindividual variability in the degree of drug interaction between patients., Conclusions: Fluconazole given orally in a dose of 200 mg/day is associated with significant increase in bioavailability of CsA. The maximum effect occurs on day 4 after starting fluconazole. Although repeated monitoring of CsA Cmin is convenient as opposed to repeated determination of AUC, changes in Cmin may not be sensitive enough to pick up this interaction. The increase in bioavailability of CsA is unpredictable in individual patients and all patients should be monitored with AUC near day 4 of treatment to guide CsA dosage reductions.

Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult-onset nephrotic syndrome, but its pathophysiology is poorly understood. The question as to why only a subset of patients responds to treatment in unanswered. In the past few years, change of podocytic phenotype from stationary type in health to migratory type in disease has been described, of which loss of subpodocytic space is a surrogate marker. Diagnostic biopsies of adult-onset steroid-resistant calcineurin inhibitor-naïve primary FSGS cases, which were subsequently treated with tacrolimus were included in this retrospective study conducted from 2011 to 2013. The ultrastructure of all cases was studied in detail, especially in context to the presence or absence of subpodocytic space. In the present study, we have compared presence or absence of subpodocytic space in tacrolimus-responsive versus tacrolimus-resistant cases to identify potential electron microscopic features predictive of response to treatment, of which loss of subpodocytic space indicating migratory phenotype is the most important and consistent feature. The present series included 7 tacrolimus responsive cases (includes two cases with partial response) and seven tacrolimus-resistant cases. The tacrolimus-resistant patients were of older age, had a longer duration of illness, and a lower eGFR as compared to tacrolimus responsive cases. The subpodocytic space was preserved in patients on tacrolimus with complete remission and lost in patients with partial response and tacrolimus-resistant cases. [ABSTRACT FROM AUTHOR]

Non-depleting antibody induction has the best safety profile in transplant recipients without an increased risk of infection or malignancy. This observational study was performed in intermediate immunologic risk live donor renal transplants to assess basiliximab efficacy in patients on tacrolimus, mycophenolate, and prednisolone immunosuppression. A total of 46 patients on basiliximab induction were compared to risk matched 56 controls at the end of 6 and 12 months post.transplant. An additional cost of approximately Rs. 100,000/patient was incurred by the basiliximab group. The incidence of biopsy proven acute rejection in the control group (12.5%, 6 months and 20.5%, 1 year) and the basiliximab group (13%, 6 months and 18.9%, 1 year) was similar. At 6 months, there was a non.significant trend toward more steroid sensitive rejections and better glomerular filtration rate preservation in the basiliximab group (83.3%, 71.9 ml/min) versus the control group (28.6%, 62.2 ml/min). However, this difference was lost at 1 year (70.1 ml/min vs. 67.6 ml/min). The incidence of infections was similar and none of the patients had a malignancy. Death censored graft survival (94.6% basiliximab and 94.8% control) and the mean number of hospitalizations for all reasons at the end of 1 year were not different among the two groups. In our study, basiliximab induction did not confer an additional advantage in the intermediate risk live donor transplants in patients on tacrolimus and mycophenolate based triple drug immunosuppression. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication of organ transplantation. This study was a retrospective analysis of 2000 patients who underwent renal transplantation over a period of 30 years (1980-2010). Forty malignancies were diagnosed in 36 patients. Of these, 29 patients (1.45%) had PTLD (7 females, 22 males) accounting for 72.5% of all malignancies after transplantation. Twenty.two (75.8%) developed non-Hodgkin lymphoma and seven patients (24.2%) had myeloma. Diagnosis was made by biopsy of the involved organ in 21 patients (72.4%) and aspiration cytology in five patients (17.2%). In three patients, the diagnosis was made only at autopsy. Mean age at the time of diagnosis of PTLD was 41.9 years (range 21.69 years). Time interval from transplantation to the diagnosis of PTLD ranged from 3 months to 144 months with a median of 48 months. Only five patients (17.2%) developed PTLD within a year of transplantation. Twelve patients developed PTLD 1-5 years and 12 patients 5-10 years after transplantation. Organ involvement was extra nodal in 18 patients (82%). Thirteen (59%) patients had disseminated disease and nine (41%) had localized involvement of a single organ (brain-3, liver-1, allograft-1, perigraft node-1, retroperitoneal lymph nodes-3). Infiltration of the graft was noted in two patients. Patients with myeloma presented with backache, pathological fracture, unexplained anemia or graft dysfunction. PTLD was of B cell origin in 20 cases (70%). CD 20 staining was performed in 10 recent cases, of which 8 stained positive. Of the 26 patients diagnosed during life, 20 (69%) died within 1 year of diagnosis despite therapy. In conclusion, PTLD is encountered late after renal transplantation in the majority of our patients and is associated with a dismal outcome. The late onset in the majority of patients suggests that it is unlikely to be Epstein Barr virus related. [ABSTRACT FROM AUTHOR]

The multinational observational study in transplantation (MOST) was undertaken with the objective of documenting immunosuppressive treatment options and the clinical outcomes of their use under conditions of normal clinical practice in large population of transplant recipients. 1204 patients (964 denovo and 195 on maintenance therapy) at nine renal transplant centers were enrolled throughout India; to study the impact of different immunosuppressive regimens use in combination with Neoral. Globally 20243 patients (14993 evaluatble patients) (GLOBAL MOST Group) were available for comparison. All patients received Neoral based therapy (55% Neoral + Azathioprine + Steroid; 33% Neoral + MMF + Steroid). Mean follow up was 19, 6, 13.9 months. The incidence of AR, BPAR and BPCR were 18,10 and < 10% respectively. Patients receiving Neoral based MMF therapy showed significantly higher AR (27% vs 12%) and more so at 4th and 52 year, quite in contrast to the global data. Between 1-5 years mean dose of Neoral was 1.5 to 2.5 mg/kg and MMF 750 mg to 1.2 gms/day amongst Indian patients in contrast to 2.5-3 mg/kg of Neoral and 1.5 to 1.8 gms/day of MMF in the global data. This is largest multicentric data in India showing that low dose of MMF with Neoral leads to higher rates of acute rejections especially late acute rejections. [ABSTRACT FROM AUTHOR]