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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]

Hepatitis C virus (HCV) infection in renal allograft recipient is associated with increased morbidity and mortality. At present, only few studies related to treatment and outcomes of HCV-infected renal allograft recipients with DAAs have been published. We aimed the study to assess the efficacy and safety of sofosbuvir-based regimens in HCV-infected renal allograft recipients. We analyzed data of 22 eligible HCV-infected renal allograft recipients (14 genotype-3, 6 genotype-1, one each genotype-2 and 4) who were treated with DAAs at our institute. DAA regimen included sofosbuvir and ribavirin with or without ledipasvir or daclatasvir for 12--24 weeks. Patients were followed up for 24 weeks after completion of treatment. A rapid viral response of 91%, end of therapy response of 100%, and sustained viral response at 12 and 24 weeks of 100% with rapid normalization of liver enzymes were observed. Therapy was well tolerated except for ribavirin-related anemia. A significant decrease in tacrolimus trough levels was observed and most patients required increase in tacrolimus dose during the study. Treatment with newer DAAs is effective and safe for the treatment of HCV-infected renal allograft recipients. [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]

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]

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]

Background Acute graft pyelonephritis (AGPN) is thought to affect graft and patient survival among renal transplant recipients. The objective was to compare outcomes among early AGPN (< 6 months from transplant) versus late AGPN (> 6 months from transplant). Methods This retrospective study analyzed 150 patients with AGPN dividing them into early and late AGPN from 2008 to 2016. Predictors of graft loss and mortality were compared using logistic regression analysis. Graft survival and patient survival were analyzed using Kaplan-Meyer survival plots. Results 55.3% (n = 83) had early AGPN and 44.7% (n = 67) had late AGPN. In early AGPN group, 13.3% had CMV disease on follow up compared to 3% in late AGPN group (p < 0.05). 26.5% had history of prolonged Foley's catheterization (> 5 days), 38.6% had prolonged DJ stent in-situ (> 2 weeks) following transplant surgery in the early AGPN compared to 7.5% and 19.4% respectively in the late AGPN group (p < 0.05). Recurrent GPN was more common in the late AGPN group – (35.8% versus 18.1%). Presence of renal abscess was predictive of graft loss in Univariate analysis (HR-6.12, p < 0.004). There was decreased death censored graft survival in the early AGPN group (p-0.035) with no significant difference in patient survival among the two groups. Conclusion Occurrence of early AGPN had a significant impact on long term graft survival in renal transplant recipients with no significant effect on patient survival. This study underlines the paramount importance of the prevention of UTIs in renal transplant recipients. [ABSTRACT FROM AUTHOR]

Introduction: Living kidney donation is a complex psychological experience for donors. The present study examined the psychosocial impact of kidney donation on donors. Methods: The retrospective study included 506 donors who donated a kidney between 2010 and 2018 at a transplant centre in India. These donors responded via a donor insight questionnaire about their hospital anxiety, and their possible level of depression. The information included socio-demographic form with multiple information. The health survey was used periodically evaluate the psychosocial impact among donors following donation, including the transplant outcomes. Results: The majority of donors were females (79.4%). There was a significant improvement in the quality of life among donors (SF-36) following the donation of a kidney, especially among those donors who maintained good graft functions themselves as well as those who were informed about good kidney function in transplanted recipients. These donors showed a lesser degree of depressive and anxiety scores (HAD score 3.5 and BDI II 4.8) than donors who had problems themselves and/or whose donated kidneys did not function well. Most living donors (89.1%) felt that the act of donation had a positive impact on their lives and those donors would encourage others to donate a kidney. Overall, the graft outcomes impacted the donor's state of mind. Conclusion: The study showed a very positive impact of the acknowledgment of the donor by the recipient, especially those donors whose kidney transplants were well functioning. The state of depression, anxiety, and psycho-social outcomes correlated with the graft outcomes. Donors showed positive insight towards donation, with inner conscience still conclusively willing to donate and encourage others. [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]

Despite kidney transplantation (KT) being considered as the best treatment modality for end-stage renal disease (ESRD), patient and graft survival in the elderly population is poorer than younger individuals. Many authors argue that prolonged life expectancy outweighs the risk of remaining on dialysis, but few studies had compared the treatment modalities, especially with peritoneal dialysis (PD). A retrospective study was conducted at a tertiary care institute to compare outcome of elderly ESRD patients, who received KT with those continued on PD; and to evaluate the predictors of patient survival. Patient survival at 1 year was (76.2% vs. 91.1%); 5 years (53.7% vs. 21.8%); and 10 years (35.6% vs. 0.00%) among KT and PD population, respectively. Infection was the most common cause of death among KT group (35 [41.2%] vs. 34 [28.2%]) while cardiovascular mortality in PD group (55 [46.2%] vs. 7 [8.2%]). Technique survival at 1, 5, and 10 years in PD group was 92.8%, 58.5%, and 0%, respectively. Similarly, graft survival at 1, 5, and 10 years in KT group was 98.7%, 90.2%, and 90.2%, respectively. Multivariate analysis showed body mass index (BMI) (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82-0.93, p < 0.001), and albumin (HR 0.55, 95% CI 0.37-0.80, p = 0.002) were significant predictors of survival. In the 1st year, patient survival was better in PD than KT, but after adjustment for BMI and albumin, both short-term and long-term survival in elderly KT group was better than that of PD. Hence, elderly ESRD patients should not be barred from KT just because of age. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis C virus (HCV) infection is a common cause of liver disease in post-renal transplant period and causes poor patient and graft survival. We analyzed the effects of antiviral therapy using ribavirin monotherapy or ribavirin in combination with interferon (IFN)-alpha in our kidney transplant recipients with chronic hepatitis C. Methods: Total of 14 patients received antiviral therapy, all of whom had stable graft function, raised aminotransferases and positive HCV viremia at the start of treatment. Eight patients received ribavirin alone for a period of six months to two yr, in doses of 400–800 mg daily. Five patients received IFN-alpha therapy for a period of two months to 1.5 yr, in doses of 1.5 million units daily or three million units thrice weekly with ribavirin. One patient received pegylated IFN 50 μg once weekly in combination with ribavirin. The response was seen in terms of biochemical and virological improvement at the end of study period. Results: In patients treated with ribavirin alone (n = 8), mean alanine aminotransferase (ALT) levels before and after treatment were significantly different (198.4 ± 147.6 and 104.8 ± 66.5 IU/L respectively; p < 0.05). ALT levels normalized completely in three patients at the end of treatment, improved in three patients and deteriorated in two. Only in one of eight patients on ribavirin alone, HCV-RNA became negative after six months of treatment while in the rest (n = 7) HCV-RNA continued to be positive. In subjects on IFN plus ribavirin (n = 6), the mean ALT levels decreased significantly (from 280.2 ± 114.9 IU/L at baseline to 71 ± 49 IU/L at end of therapy; p < 0.05). Two patients had sustained remission (33.3%) on IFN plus ribavirin (persistently negative HCV-RNA), two patients relapsed after initial remission and in two patients treatment was stopped after two months because of graft dysfunction. Totally four patients developed graft dysfunction at some time during the course of IFN therapy (66.6%), but it was discontinued in only two (33.3%). All patients regained normal creatinine levels after discontinuation of IFN, although one patient developed chronic allograft nephropathy as shown by kidney biopsy. Four patients in IFN group developed leucopenia. Two patients developed severe anemia one of whom required blood transfusion and one developed severe flu-like syndrome requiring stoppage of therapy. Conclusion: Ribavirin monotherapy in renal transplant recipients with chronic hepatitis C infection results in good biochemical response but is not associated with virological clearance. IFN in combination with ribavirin is effective in two-thirds of patients after a minimum therapy of six months, but it is poorly tolerated, results in graft dysfunction in significant number of patients, and relapse can occur after stopping treatment. [ABSTRACT FROM AUTHOR]

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]