Donor-derived Ehrlichiosis: 2 Clusters Following Solid Organ Transplantation.

Ehrlichiosis has been infrequently described as transmissible through organ transplantation. Two donor-derived clusters of ehrlichiosis are described here. During the summer of 2020, 2 cases of ehrlichiosis were reported to the Organ Procurement and Transplantation Network (OPTN) and the Centers for Disease Control and Prevention (CDC) for investigation. Additional transplant centers were contacted to investigate similar illness in other recipients and samples were sent to the CDC. Two kidney recipients from a common donor developed fatal ehrlichiosis-induced hemophagocytic lymphocytic histiocytosis. Two kidney recipients and a liver recipient from another common donor developed ehrlichiosis. All 3 were successfully treated. Clinicians should consider donor-derived ehrlichiosis when evaluating recipients with fever early after transplantation after more common causes are ruled out, especially if the donor has epidemiological risk factors for infection. Suspected cases should be reported to the organ procurement organization and the OPTN for further investigation by public health authorities.

Deep end-to-end rolling shutter rectification.

CMOS sensors employ a row-wise acquisition mechanism while imaging a scene, which can result in undesired motion artifacts known as rolling shutter (RS) distortions in the captured image. Existing single image RS rectification methods attempt to account for these distortions by using either algorithms tailored for a specific class of scenes that warrants information of intrinsic camera parameters or a learning-based framework with known ground truth motion parameters. In this paper, we propose an end-to-end deep neural network for the challenging task of single image RS rectification. Our network consists of a motion block, a trajectory module, a row block, an RS rectification module, and an RS regeneration module (which is used only during training). The motion block predicts the camera pose for every row of the input RS distorted image, while the trajectory module fits estimated motion parameters to a third-order polynomial. The row block predicts the camera motion that must be associated with every pixel in the target, i.e., RS rectified image. Finally, the RS rectification module uses motion trajectory and the output of a row block to warp the input RS image to arrive at a distortion-free image. For faster convergence during training, we additionally use an RS regeneration module that compares the input RS image with the ground truth image distorted by estimated motion parameters. The end-to-end formulation in our model does not constrain the estimated motion to ground truth motion parameters, thereby successfully rectifying the RS images with complex real-life camera motion. Experiments on synthetic and real datasets reveal that our network outperforms prior art both qualitatively and quantitatively.

BK virus nephropathy in simultaneous pancreas kidney transplant: a potentially preventable cause of kidney allograft loss.

More than half of the simultaneous pancreas kidney transplant (SPK) patients afflicted with BK virus nephropathy (BKVN) lose their kidney allograft. Fear of pancreatic rejection limits the ability to reduce immunosuppression; this may result in inadequate treatment of BKVN. This single-center retrospective review included 138 SPK patients who underwent periodic BKV screening and were managed with IS reduction alone as a treatment of choice for BKVN. All patients underwent rabbit anti-thymocyte globulin (rATG) induction and were maintained on tacrolimus/sirolimus or mycophenolate. The incidence of BKVN was 4.4%. BKVN was diagnosed at a median of 11 months; mean serum creatinine 2.1 mg/dL and the geometric mean BK serum viral load at diagnosis 1,758,000 DNA copies/mL. Median time to BKV clearance was 5.6 months; there was 96% reduction in the mycophenolate dose, 100% reduction in sirolimus, and 40% reduction in the tacrolimus blood level at BKVN clearance. No BKVN-related kidney failure was noted, and patients retained excellent kidney and pancreatic allograft function till last follow-up (43 months). BKVN in SPK is a potentially preventable cause of end-stage kidney disease, and IS reduction alone is an acceptable treatment modality in SPK without a higher risk of kidney/pancreas allograft loss as long as close monitoring can be ensured.

Early findings of prospective anti-HLA donor specific antibodies monitoring study in pancreas transplantation: Indiana University Health Experience.

The significance of donor-specific antibodies (DSA) is not well known in the setting of pancreas transplantation. Since December 2009, we prospectively followed pancreas transplant patients with single-antigen-luminex-bead testing at one, two, three, six, and then every six months for the first two yr. Thirty-five of the 92 patients that underwent pancreas transplantation (13 pancreas-alone [PTA], 20 with a kidney [SPK], and two after a kidney [PAK]) agreed to participate in study. Median age at transplant was 45 yr and follow-up was 23 months. Majority were Caucasian (n = 33) and male (n = 18). Rabbit anti-thymocyte globulin induction was used. Median HLA-mismatch was 4.2 ± 1.1. Eight patients (7SPK, 1PAK) developed post-transplant DSA at median follow-up of 76 d (26-119), 1 SPK had pre-formed DSA. Seven patients had both class I and class II DSA, one with class I and one with class II only. Mean peak class I DSA-MFI was 3529 (±1456); class II DSA-MFI was 5734 (±3204) whereas cumulative DSA MFI (CI + CII) was 9264 (±4233). No difference was observed in the patient and donor demographics among patients with and without DSA. One patient in non-DSA group developed acute cellular rejection of pancreas. From our data it appears that post-transplant DSA in pancreas allograft recipients may not impact the early-pancreatic allograft outcomes. The utility of prospective DSA monitoring in pancreatic transplant patients needs further evaluation and long-term follow-up.

A new flow cytometry assay identifies recipient IgG subtype antibodies binding donor cells: increasing donor availability for highly sensitised patients.

Objectives: There are four immunoglobulin (IgG) subtypes that have varying complement-activating ability: strong (IgG3 and IgG1) and weak (IgG2 and IgG4). The standard flow cytometric crossmatch (FCM) assay does not distinguish between the various subtypes of the IgG molecule. This study outlines the development and use of a novel cell-based IgG subtype-specific FCM assay that is able to detect the presence of and quantitate the IgG subtypes bound to donor cells. Methods: A six-colour lyophilised reagent was designed that specifically detects the four IgG subtypes, as well as distinguishes between T cells and B cells in the lymphocyte population. To test the efficacy of this reagent, a retrospective evaluation of a group of highly sensitised patients awaiting heart and kidney transplant was carried out, who, because of positive standard FCM results, had been deemed incompatible with numerous prior potential donors. Results: Observations in this study demonstrate that the positive standard FCM results were mainly because of the presence of noncomplement-activating IgG2 or IgG4 antibodies. The results were supported by the absence of C3d-binding donor-specific antibodies (DSA) and a negative complement-dependent cytotoxicity crossmatch (CDC). Conclusion: Preliminary data presented in this study demonstrate the reliability of the novel IgG subtype assay to detect the presence of pretransplant, complement-activating antibodies bound to donor cells. The knowledge gained from the IgG subtype assay and the C3d-binding specificities of DSAs provides improved identification of donor suitability in pretransplant patients, potentially increasing the number of transplants.

Proteinuria and hypertension with tyrosine kinase inhibitors.

Tyrosine kinases are important for the development of pathological angiogenesis, a critical factor for survival and proliferation of tumor cells. Inhibition of tyrosine kinases either through targeted binding of its ligands or inhibition of its receptor has led to significant hindrance in angiogenesis and has improved survival for several cancers. Several of these antibodies or small molecules have been approved for treatment of recurrent and resistant cancers over the last decade. Although generally well tolerated, tyrosine kinase inhibitors have been linked with development of hypertension and proteinuria. We review the literature for incidence and severity of hypertension and proteinuria among several tyrosine kinase inhibitors, their pathophysiologic mechanisms, and provide a guide for screening and management.

Optimal vitamin D, calcitriol, and vitamin D analog replacement in chronic kidney disease: to D or not to D: that is the question.

PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) are often insufficient in 25(OH) vitamin D and are almost uniformly deficient in 1,25(OH)2 vitamin D, because of decreased renal hydroxylation resulting from hyperphosphatemia and elevated fibroblast growth factor-23 (FGF-23) levels. These same abnormalities lead to secondary hyperparathyroidism for which the administration of calcitriol or vitamin D analogs has been the mainstay of therapy for decades. This review summarizes new trials of vitamin D, calcitriol, and its analogs over the last 2 years. RECENT FINDINGS: In addition to the endocrine effects of the vitamin D axis on bone and mineral metabolism, studies have demonstrated there is also extrarenal conversion of 25(OH) vitamin D to 1,25(OH)2 vitamin D in multiple cells leading to autocrine effects. This advance has led to the speculation that CKD patients may also need to be supplemented with ergocalciferol or cholecalciferol. Unfortunately, to date, the majority of interventional studies have focused on biochemical end points. There are no randomized controlled trials demonstrating that therapy with any formulation of vitamin D results in improved patient level outcomes. SUMMARY: Despite the physiologic importance of vitamin D in health and disease, more research is required to determine which vitamin D derivative is required for optimal health in CKD patients.

Statins for prevention of contrast-induced nephropathy in patients undergoing non-emergent percutaneous coronary intervention.

AIM: Oxidative stress and ischaemia are suggested as possible mechanisms of contrast-induced nephropathy (CIN). Statins may offer renoprotection in both acute and chronic kidney diseases because of their antioxidant and anti-inflammatory properties. We investigated whether use of statins before non-emergent percutaneous coronary intervention (PCI) reduces the incidence of CIN. METHODS: We retrospectively evaluated 540 consecutive adult patients who underwent non-emergent PCI over a 3 year period at a tertiary care centre. CIN was defined as 25% or 44 mmol/L increase from baseline creatinine at 48-72 h. In addition, we classified patients based on Mehran score for risk of development of CIN and analysed the effect of statins. RESULTS: Three-hundred and fifty-three patients met inclusion criteria. Two-hundred and thirty-nine patients were taking statins before PCI and 114 were not. Baseline characteristics were similar for both groups. CIN occurred in 75 patients (21.2%). There was a higher incidence of CIN in patients on statins as compared with patients not on statins (24.7% vs 14%; 95% CI: 1.09-3.67; P = 0.02). However, propensity-based adjustment for receipt of statins revealed no significant differences in CIN between both groups (OR: 1.6; 95% CI: 0.87-3.22; P = 0.12). Multivariate logistic regression revealed Mehran score to be independently predictive of CIN. None of the patients who developed CIN required dialysis. CONCLUSIONS: Statin use before non-emergent PCI is not associated with reduction in CIN. Further randomized controlled trials based on proper risk adjustment for development of CIN are needed.

Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized and observational studies.

BACKGROUND: Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with significant morbidity and mortality. Controversy exists regarding whether an off-pump technique can reduce post-CABG renal injury. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adult patients undergoing CABG. SELECTION CRITERIA FOR STUDIES: MEDLINE, EMBASE, Cochrane Renal Library, and Google Scholar were searched in May 2008 for randomized controlled trials (RCTs) and observational studies comparing off-pump CABG (OPCAB) with conventional CABG (CAB) for renal outcomes. Studies involving patients on long-term renal replacement therapy (RRT) were excluded. INTERVENTION: OPCAB. OUTCOMES: Primary outcomes were overall AKI and AKI requiring RRT. RESULTS: 22 studies (6 RCTs and 16 observational studies) comprising 27,806 patients met the inclusion criteria. The pooled effect from both study cohorts showed a significant reduction in overall AKI (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.43 to 0.76; P for effect < 0.001; I(2) = 67%; P for heterogeneity < 0.001) and AKI requiring RRT (OR, 0.55; 95% CI, 0.43 to 0.71; P for effect < 0.001; I(2) = 0%; P for heterogeneity = 0.5) in the OPCAB group compared with the CAB group. In RCTs, overall AKI was significantly reduced in the OPCAB group (OR, 0.27; 95% CI, 0.13 to 0.54); however, no statistically significant difference was noted in AKI requiring RRT (OR, 0.31; 95% CI, 0.06 to 1.59). In the observational cohort, both overall AKI (OR, 0.61; 95% CI, 0.45 to 0.81) and AKI requiring RRT (OR, 0.54; 95% CI, 0.40 to 0.73) were significantly less in the OPCAB group. RCTs were noted to be underpowered and biased toward recruiting low-risk patients. Sensitivity analysis restricted to good-quality studies showed a significant reduction in AKI. LIMITATIONS: Lack of uniform AKI definition in the included studies, heterogeneity for overall AKI outcome. CONCLUSIONS: Analysis of the current evidence suggests a reduction in AKI using the OPCAB technique; however, studies lack consistency in defining AKI. Available RCTs are underpowered to detect a difference in AKI requiring RRT; evidence from observational studies suggests a reduction in RRT requirement. Future studies should apply a standard definition of AKI and target a high-risk population.

Acute and Chronic Allograft Dysfunction in Kidney Transplant Recipients.

Allograft dysfunction after a kidney transplant is often clinically asymptomatic and is usually detected as an increase in serum creatinine level with corresponding decrease in glomerular filtration rate. The diagnostic evaluation may include blood tests, urinalysis, transplant ultrasonography, radionuclide imaging, and allograft biopsy. Whether it occurs early or later after transplant, allograft dysfunction requires prompt evaluation to determine its cause and subsequent management. Acute rejection, medication toxicity from calcineurin inhibitors, and BK virus nephropathy can occur early or later. Other later causes include transplant glomerulopathy, recurrent glomerulonephritis, and renal artery stenosis.

Trends in the management and outcomes of kidney transplantation for autosomal dominant polycystic kidney disease.

Background. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure. The objective of this study was to evaluate a longitudinal experience of kidney transplantation for ADPKD. Methods. A single center retrospective review of patients undergoing kidney transplantation was conducted, with comparisons across two time periods: early (02/2000-04/2007, n = 66) and late (04/2007-08/2012, n = 67). Results. Over the 13.5-year study period, 133 patients underwent transplantation for ADPKD. Overall, no significant difference between the early and late group with regard to intraoperative complications, need for reoperation, readmissions within 30 days, delayed graft function, and mortality was noted. There was a trend towards increase in one-year graft survival (early 93.1% versus late 100%, P = 0.05). In the early group, 67% of recipients had undergone aneurysm screening, compared to 91% of recipients in the late group (P < 0.001). Conclusions. This study demonstrates consistent clinical care with a trend towards improved rates of one-year graft survival. Interestingly, we also note a significantly higher use of cerebral imaging over time, with the majority that were detected requiring surgical intervention which may justify the current practice of nonselective radiological screening until improved screening criteria are developed.

Allocation of resources for organ transplantation.

Over the last 6 decades, organ transplantation has achieved great success to become standard therapy for the treatment of patients with end-stage organ failure. With this success has emerged candidate wait lists that greatly outnumber the current supply of deceased donor organs. The increasing number of candidates and transplants performed has resulted in an organ allocation process that occurs at a local, regional, and sometimes national level. A brief description of the history is presented as well as the methodologies involved in allocation of a donor organ to a single recipient.

Impact of tacrolimus-sirolimus maintenance immunosuppression on proteinuria and kidney function in pancreas transplant alone recipients.

BACKGROUND: Nephrotoxicity is a major complication with immunosuppression regimens used in transplantation. Calcineurin inhibitor-sparing or reduction regimens using sirolimus (SRL) have shown variable success in kidney transplantation. There is limited data on the role of SRL on native kidney function in pancreas transplantation. METHODS: All patients undergoing pancreas transplantation from 2003 to 2010 were enrolled in this study (n=65). Patient demographic characteristics were identified and divided into two groups: those receiving tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and those maintained on a regimen of Tac and SRL with or without MMF. The slopes for estimated glomerular filtration rate (eGFR), serum creatinine level (sCr), and proteinuria changes over time were assessed between groups. Urine protein and creatinine ratio (uPr/uCr) was used to assess proteinuria. RESULTS: There was no difference in baseline demographic characteristics. Patients were followed for a median of 3 years. Baseline sCr and eGFR were similar between groups. Differences in uPr/uCr and rate of change in sCr and eGFR were not significant between the groups overall or for any specific time. There was worsening of sCr, eGFR, and uPr/uCr within the groups over the period of study. There were no significant differences when groups were split by age or gender or when the SRL group was split further based on MMF inclusion. CONCLUSIONS: Our study findings suggest that using a Tac-SRL regimen in patients with pancreas alone transplantation is a safe approach and may not lead to worsening proteinuria and kidney function when compared with regimens using Tac with MMF.

Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency is highly prevalent among patients with chronic kidney disease (CKD). The benefits and harms of vitamin D supplementation (ergocalciferol or cholecalciferol) were assessed in patients with nondialysis-dependent CKD, dialysis-dependent CKD, and renal transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE (1966 to September 2009), SCOPUS (September 2009), and nephrology conference proceedings were searched for relevant observational and randomized controlled trials (RCTs). Treatment effects were summarized as mean differences (MDs) with 95% confidence intervals (CIs) using a random effects model. Separate analyses were conducted for observational studies and RCTs. RESULTS: Twenty-two studies (17 observational and 5 RCTs) were included. There was a significant improvement in 25-hydroxyvitamin D (MD 24.1 ng/ml, 95% CI 19.6 to 28.6) and an associated decline in parathyroid hormone (PTH) levels (MD -41.7 pg/ml, 95% CI -55.8 to -27.7) among observational studies. PTH reduction was higher in dialysis patients. Among RCTs, there was a significant improvement in 25-hydroxyvitamin D (MD 14 ng/ml, 95% CI 5.6 to 22.4) and an associated decline in PTH levels (MD -31.5 pg/ml, 95% CI -57 to -6.1). A low incidence of hypercalcemia and hyperphosphatemia was reported with vitamin D supplementation. Cardiovascular and skeletal effects of vitamin D supplementation have not been studied. Included studies were mostly of low to moderate quality. CONCLUSIONS: Available evidence from low-to-moderate quality observational studies and fewer RCTs suggests that vitamin D supplementation improves biochemical endpoints. However, whether such improvements translate into clinically significant outcomes is yet to be determined.

N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta-analysis.

BACKGROUND: Clinical trials with N-acetylcysteine (NAC) in perioperative cardiovascular settings have shown inconsistent effects for renal endpoints. We aimed to systematically review these trials to ascertain its role in prevention of post-cardiovascular surgery acute renal failure. METHODS: We searched MEDLINE, EMBASE, Cochrane Renal Health Library, and Google Scholar for randomized controlled studies that evaluated NAC in adult patients undergoing cardiovascular surgery. Acute renal failure, acute renal failure requiring dialysis, and mortality were the primary outcomes. Additional outcomes studied were length of intensive care unit stay, postoperative serum creatinine, creatinine clearance, renal biomarkers, and adverse effects of NAC. RESULTS: Twelve studies comprising 1,324 patients were found to be eligible. Meta-analytic estimates showed that NAC was not associated with reduction in acute renal failure (odds ratio [OR]: 0.89, 95% confidence interval [CI]: 0.68 to 1.15), acute renal failure requiring dialysis (OR: 1.09, 95% CI: 0.57 to 2.09) or mortality (OR: 0.95, 95% CI: 0.53 to 1.71). N-acetylcysteine was well tolerated but was not associated with any reduction in the length of intensive care unit stay. It had inconsistent effects on postoperative serum creatinine, creatinine clearance, and renal biomarkers. Subgroup analysis restricted to studies using intravenous NAC preparation showed a nonsignificant trend toward reduction in acute renal failure (OR: 0.81, 95% CI: 0.61 to 1.08) without any significant change in other outcomes. CONCLUSIONS: Overall analysis of the existent literature shows that NAC is not beneficial in the prevention of post-cardiovascular surgery renal dysfunction. Routine use of NAC for this indication should be avoided.

Factors associated with quality of life in outpatients with head and neck cancer 6 months after diagnosis.

BACKGROUND: Identifying patients with head and neck cancer at greatest risk of poor health-related quality of life (HRQOL) will facilitate screening for such patients and targeted interventions. METHODS: This was a cross-sectional, self-administered survey with medical record review among 65 out-patients with head and neck cancer >6 months from diagnosis and off treatment. RESULTS: Most were men (80%) and white (95%), with a mean age of 60 +/- 13 years. The most prevalent cancer type was squamous cell (88%), site was pharyngeal (40%), and stage was III or IV (80%). Lower total HRQOL was independently associated with gastrostomy (p < .001) and history of radiation therapy (p < .05)(R(2) = 0.27). Certain HRQOL subscales were also independently associated with depression, body mass index, age, and education. CONCLUSIONS: Several factors can be used to identify patients with head and neck cancer at risk for persistent reductions in HRQOL requiring intervention.