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BackgroundClinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined MethodsIn a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days ResultsRenal failure (odds ratio [OR], 3.17; P=.010), diabetes mellitus (OR, 8.11; P<.001), and prior voriconazole and/or caspofungin use (OR, 4.41; P=.033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P=.002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P=.021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P<.001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P=.023) and disseminated disease (OR, 14.6; P=.027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P=.003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables ConclusionsThe risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis

Introduction: Fungi are ubiquitous organisms and significantly alter the post-transplant course. They are a major cause of morbidity and mortality and more so in developing countries. Aims: To study the clinical profile, etiology, risk factors, treatment, and outcome of fungal infections in post-renal transplant recipients. Materials and Methods: This was a cross-sectional observational retrospective study from January 2014 to June 2017 wherein renal transplant recipients with invasive fungal infection were included and were followed. Results: Amongst 550 renal transplant recipients, 56 (10.2%) patients developed invasive fungal infection. Mean age of patients was 40.61 ± 10.06 (13-66) years and mean duration of acquiring infection post-transplant was 25.33 ± 23.65 (1-96) months. Male to female ratio was 3:1. Fever was the commonest presentation observed in 89.3% patients. Cough (76.8%), breathlessness (64.3%), sputum (55.3%), hypoxia (50%), and hemoptysis (10.7%) were other common clinical symptoms at presentation. Mean serum creatinine at presentation was 1.70 mg/dl. Most common invasive fungal infection isolated was Mucormycosis 15 (26.7%), foolwed by Aspergillosis 13 (23.2%), Pneumocystis jiroveci 12 (21.4%), Cryptococcus 6 (10.7%), Candida 4 (7.1%), Histoplasmosis 3 (5.3%), Phaeohypomycosis 2 (3.5%), and 5 (8.9%) patients had undetermined fungal etiology. Twenty (35.7%) patients had evidence of dual infection. Use of antithymocyte globulin 27 (48.2%), post-transplant diabetes mellitus 18 (32.1%), Cytomegalovirus (CMV) infection 16 (28.5%), anti-rejection therapy 9 (16%), and Hepatitis C infection 7 (12.5%) were some identified risk factors. Ten (17.8%) patients had graft loss and 12 (21.4%) patients died in the study period. Conclusions: Invasive fungal infection is a serious threat to renal transplant recipients. Patient and graft survival is significantly affected by fungal infection in developing world.

Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixtyone percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a calcineurin-inhibitor agent (P=.003). In amultivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.

Background Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians. Methods GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe’s and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations. Results A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m 2 . All creatinine-based eGFR equations overestimated GFR ( p  < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPI Cys was not significantly different from mGFR ( p  = 0.38). The CKD-EPI Cys exhibited lowest bias [mean bias: −3.53 ± 14.70 ml/min/1.73m 2 (95% CI: -0.608 to −0.98)] and highest accuracy (P 30 : 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90–134.50) ml/min/1.73m 2 . Conclusion Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

Background. We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients. Methods. The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study. Results. In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy. Conclusions. This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.

Background.Cryptococcosis occurring _30 days after transplantation is an unusual event, and its characteristics are not known. Methods.Patients included 175 solid-organ transplant (SOT) recipients with cryptococcosis in a multicenter cohort. Very early-onset and late-onset cryptococcosis were define as disease occurring _30 days or 130 days after transplantation, respectively. Results.Very early-onset disease developed in 9 (5%) of the 175 patients at a mean of 5.7 days after transplantation. Overall, 55.6% (5 of 9) of the patients with very early-onset disease versus 25.9% (43 of 166) of the patients with late-onset disease were liver transplant recipients (Pp.05). Very early cases were more likely to present with disease at unusual locations, including transplanted allograft and surgical fossa/site infections (55.6% vs 7.2%; P! .001). Two very early cases with onset on day 1 after transplantation (in a liver transplant recipient with Cryptococcusisolated from the lung and a heart transplant recipient with fungemia) likely were the result of undetected pretransplant disease. An additional 5 cases involving the allograft or surgical sites were likely the result of donor-acquired infection. Conclusions.A subset of SOT recipients with cryptococcosis present very early after transplantation with disease that appears to occur preferentially in liver transplant recipients and involves unusual sites, such as the transplanted organ or the surgical site. These patients may have unrecognized pretransplant or donor-derived cryptococcosis.

Background.Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known. Methods.We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis. Results.Of 75 patients treated with polyenes as induction regimens, 55 (73.3%) received lipid formulations of amphotericin B and 20 (26.7%) received AmBd. Similar proportions of patients in both groups had renal failure at baseline (P=.94). Overall, mortality at 90 days was 10.9% in the group that received lipid formulations of amphotericin B and 40.0% in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (P=.034), renal failure at baseline (P=.016), and fungemia (P=.003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P=.007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P=.349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.02–20.80; P=.047) and fungemia (OR, 10.66; 95% CI, 2.08–54.55; P=.004) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95% CI, 0.02–0.57; P=.008). Conclusions.Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients.

Background and Aims The patients with end stage renal disease (ESRD) are at greater risk of acquiring chronic hepatitis B or C and subsequently development of liver disease. The aim of the study was to assess liver fibrosis by transient elastography (TE) and look for factors associated with change in liver stiffness measurement (LSM) with one session of hemodialysis (HD). Methods Consecutive ESRD patients on maintenance hemodialysis (MHD) with suspected liver disease were enrolled. They underwent LSM by TE before and after one session of HD. Bioelectric impedance analysis was done to evaluate the volume status at the time of TE. Results Sixty-eight patients with mean age of 40 ± 14 years were included. There was a significant reduction in LSM after HD (18.5 [95% CI 14.8–23.1] vs. 11.2 [95% CI 8.8–13.7] kPa, p  < 0.001), with a mean LSM reduction of 7.2 [95% CI 5.25–9.19] kPa. On stratification in two groups by net ultrafiltration during HD (> or < 2.5 liters [L]), change in LSM was substantially higher in patients when total fluid removed was > 2.5 L (8.6 [95% CI 5.7–11.5] vs. 5.1 [95% CI 2.9–7.5], p  = 0.05). In 18 patients who underwent liver biopsy, LSM after HD performed better at detecting significant fibrosis, with area under receiver operating characteristics curve 0.71 [95% CI 0.46–0.97], versus 0.64 [95% CI 0.38–0.90], respectively. An LSM value of 12.2 kPa after HD was 71% sensitive and 74% specific for detection of significant fibrosis (≥ F2), while values less than 9 kPa ruled out significant fibrosis with a sensitivity and specificity of 37 and 100%, respectively. Conclusion LSM by TE decreases significantly after HD in patients with ESRD on long-term MHD. Hence, TE should be done after HD for accurate assessment of liver fibrosis.

Background: Repeat renal biopsy is usually done for lupus nephritis (LN) flare or resistant disease. We analyzed the changes between first and repeat biopsy and the contribution of repeat biopsy on renal outcome in LN patients. Methods: This was a retrospective study carried out at a tertiary care center in India. Sixty-two LN patients who underwent repeat biopsy for clinical indications, between January 2012 to December 2016, were included. Clinical and histological parameters at first and second biopsies were compared. Logistic regression analysis was done to determine parameters on repeat biopsy predicting response at last visit. Results: Repeat biopsy was done for relapse in 56% and for resistant disease in 44% patients. Seven (13.7%) out of 51 patients with baseline proliferative histology converted to non-proliferative lesion on second biopsy, while 2 (18.2%) out of 11 with baseline non-proliferative lesion converted to proliferative lesion on second biopsy. On repeat biopsy, the presence of endocapillary proliferation decreased, whereas glomerulosclerosis, interstitial fibrosis/tubular atrophy (IFTA), and glomerular basement membrane thickening increased. At the last visit (median follow-up of 38.6 months after first biopsy and 13.8 months after second biopsy), 79% of patients were in remission and 6.5% needed renal replacement therapy. The presence of IFTA >30% and thrombotic microangiopathy (TMA) on second biopsy independently predicted response at last visit. Conclusion: In Indian patients with LN, chronicity markers and superimposed membranous pattern increased on repeat biopsy done for clinical indications. The presence of IFTA and TMA on second biopsy predicted response at last visit.

Granulomatosis with polyangiitis (GPA) commonly affects upper/lower respiratory tract and kidneys. It causes necrotizing vasculitis of small and medium-sized blood vessels. Gastrointestinal (GI) involvement is an uncommon manifestation of GPA, and presentation with predominant GI manifestation is noteworthy. We report a case of 50-year-old male with melena due to GI vasculitis along with other systemic involvement. The patient was treated with pulse methylprednisolone, cyclophosphamide, and plasmapheresis. To manage the refractory GI bleed, the patient underwent surgical resection, and the histology of the surgical specimen confirmed necrotizing vasculitis.