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With the increased incidence and survival of lung transplant (LTx) recipients, the risk for chronic sequelae such as chronic kidney disease (CKD) is on the rise. Data on the long-term renal outcome are scarce. We performed a retrospective chart review of 171 adults with LTx from January 1, 2014, to January 1, 2019. Primary outcomes were prevalence of CKD/end-stage renal disease, acute kidney injury (AKI) as a risk factor for future CKD, and all-cause mortality in recipients with CKD compared with the non-CKD group. Secondary outcomes were frequency of utilization of modalities for CKD (urinalysis, imaging, biopsy, nephrology consultations). Baseline median creatinine and estimated glomerular filtration rate (eGFR) were 0.8 mg/dL and 90 mL/min/1.73 m2, respectively. Of the participants, 60% (96 of 161), 67% (102 of 153), 79% (37 of 47), 86% (10 of 12) had CKD at the end of 6, 12, 36, and 60 months, respectively, and 16% were on dialysis at the end of the study period; 3% received a subsequent renal transplant, and 27% mortality was noted over a 5-year follow-up period. The odds of CKD development in patients with an AKI during index hospitalization vs no AKI was 6.22 (2.87 to 13.06, P

The advent of direct-acting antiviral (DAA) therapies has allowed kidney transplantation from hepatitis C (HCV)-viremic donors into negative recipients. We evaluated the safety and feasibility of such practice when utilizing a patient's health plan to cover the cost for DAAs. Materials and methods This was a prospective, non-randomized, pilot clinical study. 30 HCV-negative participants received kidney transplant from HCV-viremic deceased donors. HCV polymerase chain reaction (PCR) was checked on day 3 post transplant, and a request for pan-genotypic DAA therapy was sent once viremia was confirmed. Primary outcomes were the percentage of patients achieving sustained virologic response defined as undetectable HCV PCR 12 weeks after therapy completion, and the percentage of patients receiving DAAs via patient's health plan. Results HCV viremia occurred in all 30 recipients. Sustained viral response was achieved in 93% of the patients. Two patients failed first-line DAAs, 1 patient due to non-compliance with the prescribed regimen while the other due to NS5A mutation. DAA therapy was successfully obtained via patient's health plan in 28/30 patients. There was no significant liver-related complication, patient death, or graft loss. Conclusion Kidney transplantation from HCV-viremic donors appears to be safe. However, challenges with obtaining DAA coverage in the United States persist.

Hydroxychloroquine (HCQ) has become the rheumatologists's "Swiss army knife" when it comes to managing the rheumatologic manifestations of SLE and other auto-immune disorders. By contrast, nephrologists are much less comfortable in managing the multifaceted effect of HCQ. As a result, nephrologists are inclined to abdicate their responsibility for HCQ management, if this therapy was initiated by a rheumatologist. This report describes such a situation, which had devastating consequences for the patient. On this basis we suggest that this report is a story worth telling, and should encourage the nephrologist to be more involved in their patients' HCQ management.

Eculizumab is an emerging therapy for atypical hemolytic uremic syndrome (aHUS). Early identification and treatment of recurrent aHUS after kidney transplantation requires a high clinical suspicion but results in improved graft function and patient outcome. We present a patient who developed recurrent aHUS after kidney transplantation that responded to eculizumab therapy. A kidney biopsy was performed to confirm resolution of thrombotic microangiopathy 8 weeks after eculizumab treatment initiation and revealed no features of thrombotic microangiopathy. Instead, the biopsy revealed monoclonal immunoglobulin G (IgG)4/2κ deposition in the glomerular tufts, vasculature, and atrophic tubular basement membranes. IgG4/2κ deposits are a rare pathologic finding following eculizumab therapy, and the long-term effect of these deposits on kidney function remains unknown. Index Words: Eculizumab, aHUS, thrombotic microangiopathy

Published data regarding the approach to management of diabetes mellitus in solid organ transplant (SOT) recipients are limited. We performed a retrospective chart review of SOT recipients with diabetes, above 18 years of age, who were usisng dulaglutide. There was a sustained, statistically significant reduction in the primary endpoints of weight, body mass index (BMI) and insulin requirement in 63 SOT recipients at 6, 12 and 24 months, respectively. A total of 59, 50 and 13 recipients were followed during 6, 12 and 24 months, with a mean paired difference for weight reduction of 2.07 (P value

A 47-year-old man with a history of deceased donor kidney transplant in May 2019 was admitted with odynophagia, pancytopaenia and neutropaenic fever. He had new tongue lesions ongoing for 2 weeks. Examination showed a 3×3 cm elevated, adherent plaque (figure 1). He has a history of resistant cytomegalovirus (CMV) viraemia with failed therapy to low-dose valganciclovir, ganciclovir and letermovir. Foscarnet led to undetectable CMV viral load, but the treatment was complicated with acute renal injury, and he was transitioned to a high-dose valganciclovir. We held his valganciclovir on admission as his CMV PCR was

The population of patients with kidney transplants in the United States is growing. The delivery of transplant care is complex, involves a multidisciplinary transplant team, and care coordination between transplant and community providers. The transplant nephrologist is central to the delivery of this care and assumes a multitude of clinical and nonclinical roles and responsibilities. With a growing population of patients requiring transplant care that spans a continuum from pretransplant referral to long-term posttransplant management, an understanding of the current state of the transplant nephrology workforce in the United States and the future that it faces is important in ensuring that current and future needs of both patients and physicians are met. In this article, we (1) review the scope of practice of the transplant nephrologist, (2) discuss the state of training in the field of transplant nephrology, (3) review the role of the referring primary nephrologist in the care of patients undergoing kidney transplant, and (4) discuss challenges and opportunities facing the transplant nephrology workforce.

Renal transplant patients on immunosuppression are at risk for malignancy. One form of malignancy that commonly affects this population is Kaposi-sarcoma. Kaposi-sarcoma is a human herpesvirus-8 (HHV-8)-driven process classically associated with skin lesions in immunocompromised patients. The pulmonary system may be involved in disseminated disease. In this case, a renal transplant patient was re-admitted with acute hypoxic respiratory failure and hemoptysis of an unclear etiology. Following a broad workup, HHV-8 PCR and a lymph node biopsy confirmed pulmonary Kaposi-sarcoma. Workup for multicentric Castleman disease was negative. The patient was treated with liposomal doxorubicin, ganciclovir, and prednisone. Her immunosuppression was changed to sirolimus and she is scheduled to complete six cycles of liposomal doxorubicin.

Purpose Acute kidney injury (AKI) has been increasingly recognized as a common post-operative complication of lung transplantation (LT). AKI incidence and severity in LT recipients has been associated with higher cost and decreased post-operative survival. To date, no study has evaluated early post-operative AKI and post-operative outcomes. We sought to evaluate the incidence of AKI in our LT program and to identify associated factors for possible intervention. Methods This study is a single center retrospective review conducted from January 2015 to March 2019 under institutional review board approval at our institution. Patients with multi-organ transplants, re-transplants, and patients who expired within 30 days of transplant were excluded. 171 patients were identified and 153 qualified for review. Our protocol adapted RIFLE criteria to identify post-operative AKI. Statistical analysis was completed analyzing incidence of AKI from post-operative days 1 to 14, with subgroup analyses of days 1 to 7 and 8 to 14. AKI status was compared with pre-specified individual covariates using Fisher's exact tests and logistic regression models with AKI status as the outcome and each covariate as the predictor. All calculations were performed using SAS 9.4 (SAS Institute, Cary, NC). Results Post-operative AKI incidence was 36.6%, and ESRD incidence was 9.8% between the years of 2015 and 2019. Survival at one year (p=0.024) and 5 years (p=0.038) following LT was significantly lower in patients with early post-operative AKI. African American recipients (p=0.014), bilateral transplant recipients (p=0.005), and those transplanted on cardiopulmonary bypass (p=0.018) were all more likely to have post-op AKI. Use of vasopressors, longer operative times, and the need for blood products within the first 24 hours of LT were also associated with AKI. The majority of renal injury occurred within the first 7 post-operative days. Conclusion Early post-operative AKI is associated with decreased 1 year and long term survival. Additionally, we identified the first 7 post-operative days to be the most likely time for patients to develop renal injury. We identified variables associated with renal hypoperfusion to be major risk factors for post-op AKI. We also identified susceptible patient populations and operative interventions associated with AKI.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are gaining popularity in the management of diabetes in solid organ transplant (SOT) recipients. There are no studies available comparing the two GLP-1RAs dulaglutide and liraglutide in SOT. We performed a retrospective chart review to assess the safety and effectiveness of these agents in adult SOT with diabetes at 6, 12 and 24 months. There were 63 and 25 recipients on dulaglutide and liraglutide, respectively. There was a sustained reduction in primary endpoints of weight, BMI and insulin requirement with dulaglutide when compared to liraglutide. Decrease in weight was 2%, 4% and 5.2% with dulaglutide and 0.09%, 0.87% and 0.89% with liraglutide at 6, 12 and 24 months respectively. BMI reduction followed the same trend in the two groups. The percentage reduction for insulin was 26% with dulaglutide and 3.6% with liraglutide. There was a 10% reduction in creatinine and a 15% increase in estimated glomerular filtration rate (eGFR) at the end of 24 months with dulaglutide. However, there was an increase in creatinine by 7% and an 8% decrease in eGFR at the end of 24 months with liraglutide.

Following primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction, microvascular perfusion is often impaired secondary to thrombotic embolization. Intracoronary (IC) fibrinolytic administration may reduce thrombotic burden and distal embolization. The ICE-T-TIMI-49 study evaluated the feasibility and safety of low-dose IC tenecteplase (TNK) during PPCI. The study randomized 40 PPCI patients to a volume matched bolus of IC TNK (4 mg) (n = 20) or IC saline placebo (n = 20) before and following PPCI. The primary end point was percent diameter stenosis of the culprit lesion following first bolus. The primary end point did not differ between IC placebo (median 100%, interquartile range [IQR] 83.0,100.0) and IC TNK (median 100% stenosis, IQR 91.0,100.0; p = 0.522). However, the proportion of patients with reduction in thrombus following first bolus tended to be greater with IC TNK (placebo: 12.5% vs IC TNK: 40.0%, p = 0.133). Following PPCI, the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (cTFC) was lower (faster) with placebo (16.0 frames [IQR 12.0,24.0] vs 24.0 frames [22.0,32.0], p = 0.045) due to a trend towards greater frequency of hyperemia (cTFC14), a marker of distal embolization (50.0% vs 8.3%, p = 0.056). There was no difference in TIMI major bleeds and no intracranial hemorrhage. In conclusion, treatment with low-dose IC TNK appears safe and well tolerated during PPCI. Although IC TNK administration did not improve percent stenosis, a trend towards reduced thrombus burden was demonstrated with less hyperemia (a marker of distal embolization). Our findings provide support for a large randomized study.

Approximately 7% of deceased donors have unknown cancer at the time of organ procurement. More than half of these have no apparent contraindication to organ donation. The commonest transmitted malignancy is renal cell cancer (19%), followed by melanoma (17%). Donor transmission of melanoma has been fatal in most cases as it is commonly metastatic at the time of diagnosis. Till date, there have been only a few cases with remission of melanoma following transplant nephrectomy and withdrawal of immunosuppression. To our knowledge, the evidence presented here is only the second case of donor-derived melanoma that was successfully treated with Ipilimumab. Our patient has the longest disease-free survival (five years) reported in the literature to date.

Objective Due to a progressive decline in beta-cell function, a considerable number of patients with type 2 diabetes mellitus (T2D) ultimately require multiple daily injections of large doses of insulin for glycemic control. Majority of studies have reported only short-term benefits of continuous subcutaneous insulin infusion (CSII) using an insulin pump in T2D. Our five-year follow-up data of CSII in T2D is one of the few studies showing persistent benefit in glucose control in this population. Research design and methods We did a chart review of patients treated with an insulin pump for five years. Inclusion criteria were: type 2 diabetes, 18-75 years of age, glycosylated hemoglobin (HbA1c) more than 6.5% (48 mmol/mol) on multiple doses of insulin (MDI > four injections per day) or more than 100 units of insulin/day, wide glycemic excursions, and intractable hypoglycemia. We identified a total of 13 patients. The primary endpoint was change in HbA1c from baseline to five years. We also reviewed the difference in weight, basal insulin requirements, hypoglycemia, and patient satisfaction questionnaire at one year. Exclusion criteria were: type 1 diabetes (T1D) and pregnancy. Results The HbA1c at five years was found to be 7.72% (61 mmol/mol) compared to a baseline of 8.89% (74 mmol/mol), p-value 0.0076. We did not find any increased risk of severe hypoglycemia, weight gain, and insulin requirement. Conclusions The beneficial effect of insulin pump persisted for five years of follow-up, suggesting it as a valuable treatment option for difficult to treat T2D.

Chronic mesenteric ischaemia is a severe disease that is often missed due to its non-specific presentation. Immunosuppressed patients are at risk for infectious gastrointestinal disease, which may further obscure the diagnosis of chronic mesenteric ischaemia. In this case, a patient’s symptoms and diagnostic workup were consistent with candida esophagitis. Worsening leukocytosis despite treatment, however, prompted re-evaluation ultimately revealing a superior mesenteric artery thrombus causing mesenteric ischaemia. The patient required urgent surgical intervention for the management of his disease.

Acute oxalate nephropathy has been associated with chronic diarrheal illness and only one case has been reported due to acute diarrhea secondary to Clostridium difficile colitis. To the best of our knowledge, this is the second case report of acute oxalate nephropathy due to C.difficile colitis. A 75-year-old man with a medical history of hypertension, type 2 diabetes mellitus, chronic kidney disease stage IV, recent C.difficile colitis was admitted for acute kidney injury with a creatinine (Cr) of 8.54 mg/dL (baseline Cr, 2.3–2.6 mg/dL). His urinalysis did not show any eosinophils, casts or crystals. Antinuclear antibody, antineutrophil cytoplasmic antibody, complement levels (C3 and C4) and hepatitis screen were negative; a renal ultrasound visualized no hydronephrosis. A kidney biopsy showed widespread tubular oxalate crystal deposition suggestive of hyperoxaluria as the cause of acute kidney injury. In conclusion, an acute diarrheal illness like C.difficile colitis can cause acute oxalate nephropathy.

Pharmaceutical agents currently used in clinical practice for early management of ST elevation myocardial infraction (STEMI) act primarily on the two pathways of clot formation: platelet aggregation and the coagulation cascade. Although percutaneous coronary intervention is the standard therapy for revascularization, new fibrinolytic drugs are being developed to provide increased safety and efficacy through a longer plasma half-life, more fibrin specificity, and resistance to plasminogen activator inhibitor-1. Antiplatelet therapies useful for early and extended management of STEMI include acetylsalicylic acid, glycoprotein IIb/IIIa inhibitors (eptifibatide, tirofiban, and abciximab), the thienopyridines (clopidogrel and prasugrel), and contemporary agents (ticagrelor, cangrelor, elinogrel, and vorapaxar). Novel therapies for long-term inhibition of thrombin formation following STEMI include factor Xa inhibitors, such as rivaroxaban and apixaban. Emerging areas of STEMI treatment include pharmacotherapy that specifically targets reperfusion injury and cardiomyoplasty, which involves the use of hematopoietic stem cell therapy or growth factors to induce proliferation and differentiation of cardiac myocytes.

Arterial and venous thrombotic states, including myocardial infarction (MI), stroke and deep vein thrombosis with subsequent pulmonary embolism, are a significant cause of cardiovascular mortality and morbidity. Factor Xa (FXa) plays a pivotal role in thrombus formation. Its inhibition following acute coronary syndromes (ACS) blocks amplification of thrombin generation and subsequent clot formation, resulting in a risk reduction in recurrent MI, stroke and death. For this reason, a predictable form of oral anticoagulation continues to be an ongoing need. Rivaroxaban , the first oral FXa inhibitor, acts by direct inhibition of FXa and does not require an antithrombin cofactor for its activity.This paper describes the pharmacokinetics (PK) of low-dose rivaroxaban tested in patients with ACS. Age, gender, renal function and body weight have no clinically significant effects on the PK of the drug in treatment of ACS. Caution should be maintained during co-administration of strong CYP3A4 inducers and inhibitors. Among patients with moderate and severe hepatic impairment and in those with associated coagulopathies, rivaroxaban however is contraindicated.The mortality benefit with low-dose rivaroxaban in ACS patients was first demonstrated in ATLAS ACS2 TIMI-51 trial. With its rapid oral bioavailability, predictable PK, low drug-drug interaction and no need for monitoring, the use of low-dose rivaroxaban in addition to dual antiplatelet therapy offers an appealing new option in improving outcomes following ACS in the modern era of novel oral FXa inhibitors.

Hyperglycemia, in both diabetic and nondiabetic patients, has a significant negative impact on the morbidity and mortality of patients presenting with an acute myocardial infarction (AMI). Contemporary evidence indicates that persistent hyperglycemia after initial hospital admission continues to exert negative effects on AMI patients. There have been a number of studies demonstrating the benefit of tight glucose control in patients presenting with AMI, but a lack of convincing clinical data has led to loose guidelines and poor implementation of glucose targets for this group of patients. The CREATE-ECLA study, which hypothesized that a fixed high dose of glucose, insulin, and potassium (GIK) would change myocardial substrate utilization from free fatty acids to glucose and therefore protect ischemic myocardium, failed to demonstrate improved clinical outcomes in AMI patients. Studies that specifically investigated intensive insulin therapy, including DIGAMI-2 and HI-5, also failed to improve clinical outcomes such as mortality. There are a number of reasons that these trials may have fallen short, including the inability to reach glucose targets and inadequate power. There is now a need for a large placebo-controlled randomized trial with an adequate sample size and adherence to glucose targets in order to establish the benefit of treating hyperglycemia in patients presenting with AMI.