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Background: The incidence of tuberculosis (TB) among transplant recipients varies from 5% to 15% across the globe. We conducted a retrospective study to identify the incidence of TB among kidney transplant recipients in our transplant unit. Materials and Methods: We assessed the patients who underwent kidney transplantation in our transplant unit during the study period from January 2014 to June 2018 and included those recipients who had bacteriologically confirmed TB. We excluded the patients who had TB before transplant and those recipients who were initiated on antituberculosis treatment (ATT) empirically. The details collected were: 1. Clinical data, the presenting symptoms, and clinical findings. 2. Diagnostic investigation: Microbiological/histopathological/radiological/bronchoalveolar lavage/fluid (pleural/peritoneal/ cerebrospinal fluid) analysis. 3. Antituberculous regimen, dose, and duration of the therapy. 4. Relapse/patient and graft outcome after treatment. Results: The total number of patients who underwent kidney transplantation during the study period was 177. TB occurred in 21 patients after transplantation. The incidence of TB in our transplant unit was 11.86%. In these 21 recipients, 8 had pulmonary TB and the remaining 13 had extrapulmonary/disseminated TB, which included two patients with disseminated TB and one patient with allograft dysfunction with thrombotic microangiopathy which was attributed to TB as it responded to first‑line antituberculous drugs. The mortality rate was 23.8%, as five patients expired. After excluding patients who expired, the graft survival at 1 year after ATT completion was 90.5%. Conclusion: For most developing nations, the World Health Organization’s “End TB Strategy” remains far from their dream. An ideal investigation to detect TB in its early stage is essential in posttransplant recipients to reduce the morbidity and mortality associated with it. [ABSTRACT FROM AUTHOR]

Introduction: Clinical use of tacrolimus has been challenging due to its narrow therapeutic index and highly variable pharmacokinetics. In this study, we compared patients who received body weight-based tacrolimus dosing pre-transplant (transplanted from 2016 to 2018) with those who received CYP3A5 genotype-based dosing (2018 to 2020). Methods: Eighty-two renal transplant recipients were non-randomly assigned to genotype-adapted or bodyweight-based tacrolimus dosing groups. The primary end point was to study the proportion of subjects who achieved the target tacrolimus C0 on post-op day 4. Secondary end points included clinical outcomes and safety. Results: The proportion of subjects who achieved the target tacrolimus C0 on postoperative days 4 and 10 were significantly higher in the adapted group, 53.6% and 47.5%, compared to 24.3% and 17% in controls, respectively (P = 0.01). Adapted group subjects achieved their first target tacrolimus C0 significantly earlier (4 days) compared to 25 days in controls (P = 0.01). The total number of tacrolimus dose modifications required in the first postop month were lower in the adapted group; 47 compared to 68 in the controls (P = 0.05). The proportion of subjects with sub-therapeutic tacrolimus exposure on postoperative day 4 was significantly higher in the controls, 56% versus 10% in the adapted group (P < 0.001). There were no significant differences between the groups in the rate of biopsy proven acute rejections, adverse events, and graft function at the end of 3 months follow up. Conclusion: Genotype-based tacrolimus dosing leads to more subjects achieving the target tacrolimus C0 earlier. However, there may be a higher risk of tacrolimus nephrotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: Tacrolimus blood levels are influenced by polymorphisms involving Cytochrome 3A subfamily (CYP3A5) and P-Glycoprotein (ABCB-1) genes. However, their role in transplant outcomes was less studied in South Indian population. We studied the prevalence and impact of these polymorphisms in renal transplant recipients from South India. Methods: An analysis of CYP3A5, ABCB1 genotype done in 101 renal transplant recipients by polymerase chain reaction was correlated with blood tacrolimus trough levels (CLIA method), weight, concentration/dose (L/D) ratio, incidence of biopsy proven early acute rejections, and tacrolimus toxicity. Results: Prevalence of CYP3A5*1/*1, *1/*3 and *3/*3 and ABCB1 (3435C>T) TT, CT, CC genotypes were 12 (11.9%), 48 (47.5%), 41 (40.6%) and 16 (15.8%), 45 (44.6%), 40 (39.6%), respectively. Mean tacrolimus level, median concentration/dose (L/D) ratio were significantly lower in homozygous (CYP3A5*1/*1-6.01 ng/mL; 48.99 ng/mL/mg/kg/day) and heterozygous expresser group (CYP3A5*1/*3-5.84 ng/mL; 68.93 ng/mL/mg/kg/day) when compared with nonexpresser group [CYP3A5*3/*3-7.46 ng/mL (P < 0.001);181.3 ng/mL/mg/kg/day (P < 0.05]. No significant differences observed between the ABCB1 genotypic groups. Incidence of early acute rejections (30% vs. 9.76%; P 0.016) and tacrolimus-related toxicity (14.6% vs. 5%; P 0.039) were significantly higher in CYP3A5 expressers and nonexpressers, respectively. No correlation observed between the ABCB1 polymorphisms between rejection episodes or tacrolimus renal toxicity. Among 101 patients, 40.6% were non-expressers (poor metabolizers) (*3/*3). Conclusions: CYP3A5 polymorphisms correlated with tacrolimus dose requirements and blood levels, incidence of early acute rejection, and tacrolimus nephrotoxicity. CYP3A5 polymorphism analysis prior to renal transplant will aid more precise early tacrolimus dose calculation to balance between rejection and toxicity. [ABSTRACT FROM AUTHOR]

Posttransplant lymphoproliferative disease (PTLD) is an uncommon complication of immunosuppression after solid organ transplantation. Early PTLD (<1 year after transplantation) is frequently found around the allograft, whereas late PTLD (>1 year after transplantation) does not have such a preference. 18-Fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) has clinical significance in the evaluation of PTLD. 18FDG PET-CT scan allows precise anatomic localization of FDG-avid lesions, hence helpful in staging of disease and evaluation of response to therapy. It can better characterize persistent lesions and differentiate residual tumor from fibrosis or necrosis. We present a rare case report of a perigraft PTLD developing 12 years after renal transplantation sparing the graft, in an Epstein--Barr virus-negative patient. [ABSTRACT FROM AUTHOR]

Invasive fungal infection is a complication seen in immunocompromised patients. A disseminated fungal infection has a high rate of mortality. Although disseminated infection is known to be seen in most organs, thyroid involvement is rarely reported. Hence, we report a fatal case of thyroid mucormycosis which resulted into laryngeal nerve paralysis and death of a renal allograft recipient. [ABSTRACT FROM AUTHOR]

In renal allograft recipients, cytomegalovirus (CMV) typically causes tubulointerstitial nephritis. Only rarely glomeruli are involved. We present a rare case of CMV with collapsing glomerulopathy, necrotizing glomerulonephritis, and crescent formation in a renal allograft recipient. Immunohistochemistry confirmed CMV infection. The patient was started on valganciclovir and his renal function remained stable. A repeat renal biopsy performed three months later showed morphologically normal glomeruli and CMV immunostaining was also negative. Nephropathologists have to carefully screen for CMV in cases with crescentic or collapsing glomerulopathy as the later lesions resolve after treating the underlying viral infection. This study will add on to the various glomerular changes associated with CMV infection. [ABSTRACT FROM AUTHOR]

Background Cryptosporidium is one of the common causes of infective diarrhea in post-transplant patients in endemic areas. However, data are limited on Cryptosporidium infection in recipients of solid organ transplantation. The aim of this study was to determine the incidence, disease manifestation, management, and outcome of Cryptosporidium infection in living-donor renal transplant recipients ( RTR). Methods We performed a detailed retrospective review of the data on all RTR who had diarrheal illness requiring evaluation and hospitalization, and Cryptosporidium infection. Results During the study period, 119/1235 (8.98%) RTR developed diarrhea, and Cryptosporidium was found in 34/119 (28.5%). Nine of 680 (1.3%) patients were on a cyclosporine ( CSA)-based regimen, and 25/643 (3.8%) patients were on a tacrolimus (Tac)-based regimen. The relative risk of developing Cryptosporidium infection was lower on the CSA-based regimen, compared with the Tac-based regimen (odds ratio [ OR]: 0.35, 95% confidence interval [ CI]: 0.17-0.72, P = 0.003). Twelve of the 34 patients had acute graft dysfunction, mainly caused by combined Tac toxicity and dehydration. Mean serum creatinine and trough Tac level were 2.04 ± 0.65 mg/dL and 8.24 ± 1.19 ng/dL, respectively. Nitazoxanide alone was used in 13 patients, and nitazoxanide in combination with fluoroquinolone in 21 patients, with duration of treatment ranging from 16 to 60 days. Tac was changed to CSA in 8/11 patients. The clearance of cysts and response to nitazoxanide alone were significantly lower, compared with combination therapy (61.53% vs. 95.23%, P = 0.01, 38.46 vs. 85.71%, P = 0.004, respectively). The OR for cyst clearance and response was also significantly lower with nitazoxanide alone, in comparison with combination therapy ( OR: 0.65, 95% CI: 0.34-0.92, P = 0.01, OR: 0.45, 95% CI: 0.21-0.81, respectively). Four (16%) of 24 patients with response had relapse. Conclusion Patients with Tac and mycophenolate mofetil combination therapy had a significantly high risk of Cryptosporidium infection. Cryptosporidial infection may require prolonged nitazoxanide therapy, either alone or in combination, with or without reduction in immunosuppression. [ABSTRACT FROM AUTHOR]

Dengue virus infection is an emerging global threat caused by Arbovirus, a virus from Flaviridiae family, which is transmitted by mosquitoes, Aedes aegypti and Aedes albopictus. Renal transplant recipients who live in the endemic zones of dengue infection or who travel to an endemic zone could be at risk of this infection. Despite multiple epidemics and a high case fatality rate in the Southeast Asian region, only a few cases of dengue infection in renal transplant recipients have been reported. Here, we report a case series of 8 dengue viral infection in renal transplant recipients. Of the 8 patients, 3 developed dengue hemorrhagic shock syndrome and died. [ABSTRACT FROM AUTHOR]

Infection is a leading cause of death in renal allograft recipients. Apart from the immunosuppressive drugs, immunomodulatory viral infections also predispose the recipient to many opportunistic infections. Kala-azar in renal allograft recipients is infrequently reported even in endemic areas. In majority of cases, there was delay in diagnosis and treatment. We report a case of renal allograft recipient, where we faced a diagnostic dilemma because of coinfection of cytomegalovirus and visceral leishmaniasis (kala-azar). Kala-azar was successfully treated with amphotericin B. Kala-azar should always be kept as differential diagnosis in patients with pyrexia and cytopenia, even in the absence of splenomegaly in patients residing in an endemic zone. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a frequent infectious complication in patients on renal replacement therapy, as a result of immunosuppression from uremia and drugs in the post-transplantation period. A retrospective study of all renal transplantation patients from 1989 to date was conducted. This study tried to examine the prevalence, course, and outcome of TB in renal transplant recipients. A comparison with the occurrence of TB in other modalities of renal replacement therapy was also made. We also discussed the treatment protocols for TB in this group of patients. No difference in the prevalence, age, or male/female ratio of TB was seen among the 3 modes of renal replacement therapy. TB of the lung was the more favored site of infection in patients on hemodialysis (77.3%), when compared with those on CAPD (30%) and renal transplant recipients (33.3%). In renal transplant recipients, no deaths occurred due to TB. In 7 patients there was co-infection with cytomegalovirus and in 3 patients there was Aspergillus lung infection. [ABSTRACT FROM AUTHOR]

To evaluate graft function and its effect on body composition and nutritional status of renal transplant patients using Bioelectrical Impedance Analysis. 100 patients {male 82; female 18) who underwent renal transplant between year 1997 and 2006. Their mean age was 39±10.3 years, mean height 164.2±7.6 cm and weight 58.9±9.0 kg, mean serum creatinine 1.48±.0.59 rag% and mean GFR 43.8±15.3 mljmin. GFR and body composition was assessed using multi frequency bioelectrical impedance analyzer BIOSCAN. All the patients were on 2 or 3 immunosuppressive drugs. All the patients had normal SGA scores. Data were analyzed in two steps. First analysis included comparison of patients with well matched 61 healthy controls (male 45 female 16) for age (41.7±11.3 years), sex and height (163.5±9.7 cm), with weight 63.7±12.0 kg) and serum creatinine 0.97±0.19 rag%. Patients were then divided into two groups based on GFR as calculated by Bioscan (group 1: borderline graft function GFR <40 ml]min: n= 33, X 27.8±10.2 ml/min and group 2: good graft function GFR 340 ml/minute, n =67, X 51.7±10.4 ml/min). Both groups were compared with each other. The results show that there was significant difference (p 0.000 for all variables unless specifically mentioned otherwise) between controls and PTP in weight (P.0 08), creatinine, body mass index (BMI, phase angle (PA) fat free mass (FFM, FFM% fat mass (PM) FM%, total body water (TBW %, extracellular water (ECW), ECW%, Intracellular water (ICW), ICW%, ECW/ICW, body cell mass (BCM P=0.002), GFR, extracellular solids (ECS 0.32) ECfiuid (ECF) plasma, interstitial fluid (ITSF), target fat rain (TFM P=0.021), target water min (TWM) systolic BP and diastolic BP. When groups 1 and 2 were compared, significant differences (P=0.000) were observed. Group 1 patients had low weight, PA (P=0.017), BMI (P=0.003), resting metabolic rate (RMR), FFM, TBW, ICW, ICW% (0.001), BCM, ECM (P=0.026). GFR, Protein (P=0.020), Mineral (P=0.050), Calcium, glycogen, dry weight, ECS, TFmax (P=0.046). Group 1 patients had higher ECW%, ECW/ICW compared to group 2. Though clinically all patients had normal SGA scores and were non-edematous, their intravascular compartments were expanded as depicted by high absolute values of ECW, ECW/ICW, ECF, plasma INSTFL compared to controls. Significant differences between Group 1 and Group 2 patients indicate that transplant patients with borderline graft function were more nutritionally depleted as compared to those with better GFR. Transplant patients as a group had higher systolic and diastolic blood pressure which may be related to their volume expanded status. Both nutritional deficit and volume expansion were detected objectively by BIA which is a non-invasive tool for out patient monitoring. [ABSTRACT FROM AUTHOR]

Drugs currently used to treat membranous nephropathy vary in their effectiveness among patients and can cause severe side effects. FDA has approved sirolimus for suppressing immune system of patients who have kidney transplant to reduce the risk of organ rejection. The drug does not have any certain side effects that have caused problems for patients treated with other immunosuppressants. To evaluate the safety and efficacy of a new immunosuppressive drug, sirolimus in reducing the proteinuria of patients with idiopathic membranous nephropathy resistant to previous therapy. We prospectively studied ten patients of idiopathic membranous nephropathy, who were resistant to previous therapy with ponticelli regimen (I. V. MP f/b prednisolone and cyclophosphamide every alternate month x 6 months) and of these, five were also non responsive to CsA for six months. All of them screened for the evidence of active infection before starting with sirolimus. All of them had nephrotic range proteinuria at the time of starting the therapy. Sirolimus was started with 3 mg on day 1 followed by 2 mg once a day and adjusted the dosage to achieve the target blood level (4-12 ng/ml) for a period of six months. Oral prednisolone in a dose of 1 mg/kg/day was also given along with sirolimus and tapered off slowly once remission achieved or after 8 weeks of therapy. During treatment, patients were follow up monthly for reduction of proteinuria, GFR and other clinical and laboratory parameters for the safety and effectiveness of the drug. All patients were male, age group of 20 -40 yrs, mean age of onset was 27.2 year, mean duration of illness 36 months, and all of them completed ponticelli regimen, 05 patients (50%) received CsA after they did not respond to ponticelli regimen. 7 patients (70%) received ACEI for 12 months before starting the sirolimus. Eight patients (80%) were reponders [four patients (50%) achieved complete remission (nil proteinuria), and four had partial remission (50% reduction in proteinuria)] and two (20%) were non responders. The mean time to achieve remission was 94±34 days and the mean dose of sirolimus was 2 mg per day. The mean trough levels of sirolimus were 4.7±1.8 ng/ml. The mean 24 hrs proteinuria were significantly lower from baseline of 6.25±1.63 gm/day to 0.825±0.967 gm/day (P= 0.010) and the mean serum albumin levels were increased from baseline 2.67±0.479 gm/dl to 3.28±0.538 gm/dl (P=0.108) after 94±34 days of therapy. The mean GFR values at the end of the study were similar to those prior to the starting of sirolimus 52.5±4.6 ml/mt/1.73 m² vs 49.2±2.3 ml/mt/1.73 m².The mean duration of follow up was 310±188 days. Five patients required statins for control of dyslipidemia on sirolimus therapy. Three patients had cutaneous infection (2 had fungal, 1 had scabies) which responded to antifungal and antiscabies treatment, one had developed diabetes mellitus which was controlled with oral hypoglycemic agent and diarrhea due to entamoeba histolytica. One had urinary tract infection during therapy. None of them relapsed after stopping sirolimus (mean period of 162±112 days). This is the only study so far on the safety and effectiveness of sirolimus in resistant cases of idiopathic membranous nephrotic syndrome. Our results shows that sirolimus is effective in controllong proteinuria without nephrotoxicity and serious adverse events in patients with resistant idiopathic membranous nephropathy. A prospective controlled study on large number of patients needs to be done to compare the safety and efficacy of sirolimus in idiopathic membranous nephropathy cases who are resistant to ponticelli and CsA based immunosupression regimen. [ABSTRACT FROM AUTHOR]

A response by N. Prasad to a letter to the editor regarding their article "Dengue virus infection in renal allograft recipients: a case series during 2010 outbreak" in the December 28, 2011 issue is presented.

Anti-IL-2 receptor has been proved to be effective in reducing the rate of acute rejection in kidney transplantation and also improving both the rate of graft and patient survival. In this study, we retrospectively reviewed the role of anti-IL-2 receptor (basiliximab) as induction immunosuppression. Methods: Sixty five kidney transplant recipients from living donors who received IL-2 blocker basiliximab (group 1) as induction therapy in combination with CsA, Steroid and MMF or Azathioprine, were compared with similarly matched renal transplant recipients (N=555) who did not receive induction therapy {group 2). Survival analysis was done using Kaplan- Meir analysis. Chi --square test was used to compare the outcome difference of various parameters between the two groups. Result: Both the groups were similar in terms of male to female ratio, basic disease, mean age of recipient as well as of donors. Group 1 has more no of immunologically high risk patients {2nd transplants 4.6% v/s 1.5%, P>.05}, More spousal donors {35.4% v/s 20.8 % P<0.009). Significantly more no of patients in group1 (47.7%) received MMF based immunosuppression as compared to group2 (22.6%) (P=0.016). Total no of rejections were significantly less in Group1 (15.4%) v/s 29.4% in group 2 (P=0.023, Odds ratio=0.44). More number of patients in Group 2 suffered steroid resistant rejections however the difference was not statistically significant. (11.1% in group 2 v/s 4.6% in group 1). Three percent patients suffered late acute rejections in group 1 v/s 3.9% in group 2. (P=NS). Death censored graft survival was significantly better hi group 1 at 5 yr as compared to group 2. (86% v/s 77% P<0.02). It was 100% at 1yr (group1) v/s 96%, in group 2. Actuarial patient survival at one and 5 yr was 100% and 92% in group 1 v/s 99% and 95% in group2 (P= >.05). On multivariate analysis for association with graft survival only the late acute rejections and steroid resistant rejection were independently associated with poor graft survival, whereas type of maintenance immunosuppression (MMF v/s non MMF), use of induction therapy and total no of acute rejection episodes had no association. Conclusions: The use of anti-IL-2 receptor antibodies (basiliximab) as induction immunosuppression in immunologically high-risk patients results in the significantly better prevention of acute rejection, and 5yr graft survival. It also results in reduced severity of acute rejection. [ABSTRACT FROM AUTHOR]