In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes ...equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end‐stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.
The authors summarize data from recent literature on clinical outcomes of increasing utilization of kidneys from unconventional and higher‐risk deceased donors.
Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute ...renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin‐fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non‐AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p‐value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes.
The authors show that transplanting select kidneys from deceased donors with severe acute injury results in excellent outcomes, including graft survival, and resolution of early differences in allograft gene expression for tissue damage, cell death, and inflammation.
There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection ...(ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi‐array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one‐by‐one analysis strategy to model the real clinical application of this test. Multiple three‐way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction.
This study of kidney transplantation describes a three‐way classifier based on global gene expression profiling of peripheral blood and the blood signatures of patients with excellent functioning grafts that can be used in the setting of acute kidney transplant dysfunction to accurately distinguish between biopsy‐proven acute rejection and acute dysfunction with no rejection.
Our aim was to study the impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy (IF/TA) on a 1‐year protocol biopsy in patients on rapid steroid withdrawal ...(RSW). A total of 256 patients were classified based on protocol biopsy findings at months 1 or 4. Group 1 is 172 patients with no inflammation, group 2 is 50 patients with subclinical inflammation (SCI), group 3 is 19 patients with subclinical acute rejection (SAR) and group 4 is 15 patients with clinical acute rejection (CAR). On the 1‐year biopsy, more patients in group 2 (SCI) (34%, p = 0.004) and group 3 (SAR) (53%, p = 0.0002), had an IF/TA score > 2 compared to group 1 (control) (15%). IF/TA was not increased in group 4 (CAR) (20%). The percent with IF/TA score > 2 and interstitial inflammation (Banff i score > 0) was higher in group 2 (16%, p = 0.004) and group 3 (37%, p < 0.0001) compared to group 1 (3%). In a multivariate analysis, patients in groups 2 or 3 had a higher risk of IF/TA score > 2 on the 1‐year biopsy (OR 6.62, 95% CI 2.68–16.3). We conclude that SCI and SAR increase the risk of developing IF/TA in patient on RSW.
Protocol biopsy findings during the first 4 months after kidney transplantation in a cohort of patients on rapid steroid withdrawal show that patients with earlier subclinical inflammation manifest a significantly higher risk of interstitial fibrosis and tubular atrophy on a subsequent one‐year protocol biopsy.
Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol ...on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 μg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24‐h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1‐year posttransplant. Eighty‐seven patients completed the trial. One‐year posttransplant, 29% of paricalcitol‐treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 μg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.
Paricalcitol decreases the prevalence of post‐kidney transplant hyperparathyroidism and may have beneficial effects on renal allograft histology.
The aim of this study was to determine the clinical and histologic outcomes related to transplanting kidneys from deceased donors with glomerular fibrin thrombi (GFT). We included all cases ...transplanted between October 2003 and October 2014 that had either a preimplantation biopsy or an immediate postreperfusion biopsy showing GFT. The study cohort included 61 recipients (9.9%) with GFT and 557 in the control group without GFT. Delayed graft function occurred in 49% of the GFT group and 39% in the control group (p = 0.14). Serum creatinine at 1, 4, and 12 months and estimated GFR at 12 months were similar in the two groups. Estimated 1‐year graft survival was 93.2% in the GFT group and 95.1% in the control group (p = 0.22 by log‐rank). Fifty‐two of the 61 patients in the GFT group (85%) had a 1‐month protocol biopsy, and only two biopsies (4%) showed residual focal glomerular thrombi. At the 1‐year protocol biopsy, the prevalence of moderate to severe interstitial fibrosis and tubular atrophy was 24% in the GFT group and 30% in the control group (p = 0.42). We concluded that GFT resolves rapidly after transplantation and that transplanting selected kidneys from deceased donors with GFT is a safe practice.
Deceased donor kidneys with glomerular fibrin thrombi can have excellent graft survival, as fibrin thrombi resolve by one month in most cases without any deleterious effect on renal function or biopsy findings at one year.
Abstract Background Currently, transplant patients have limited metrics available to understand transplant center quality. Graft and patient survival do not capture the patient experience, and ...patients may use more general consumer assessments of hospital care to help select transplant centers. We evaluated whether consumer assessments of hospital quality correlate with short- and long-term kidney transplant center performance. Materials and Methods CMS uses the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) to publicly report patients' perspectives on hospital care. We merged 2012 SRTR kidney transplant (n = 200 centers), HCAHPS and American Hospital Association survey data. Center performance was determined by variation in observed-to-expected (O/E) ratios for 1-month and 1-year graft failure. We used multivariate regression to determine whether HCAHPS measures correlate with center performance, after risk-adjusting for structural characteristics and volume. Results Center-specific graft failure varied significantly (30 day O/E range: 0–4.1). At 30 days, compared to average centers, cleanliness (OR = 1.26, P = .001), patient recommendation (OR = 1.18, P = .005), and high overall ratings (OR = 1.11, P = .036) predicted high performance. Poor nursing–patient communication (OR = 0.70, P = .030), lower cleanliness (OR = 0.67, P < .001), poor overall ratings (OR = 0.79, P = .038), and no recommendation (OR = 0.68, P = .019) correlated with average/low performance. There was no significant correlation between HCAHPS measures and 1-year outcomes. Conclusions The association between hospital consumer assessments of hospital care and center performance after kidney transplantation is limited. More specific metrics oriented to capturing transplant patient perspectives may be valuable in further defining transplant quality.
Summary
1
The impacts of elevated atmospheric CO2 and/or O3 have been examined over 4 years using an open‐air exposure system in an aggrading northern temperate forest containing two different ...functional groups (the indeterminate, pioneer, O3‐sensitive species Trembling Aspen, Populus tremuloides and Paper Birch, Betula papyrifera, and the determinate, late successional, O3‐tolerant species Sugar Maple, Acer saccharum).
2
The responses to these interacting greenhouse gases have been remarkably consistent in pure Aspen stands and in mixed Aspen/Birch and Aspen/Maple stands, from leaf to ecosystem level, for O3‐tolerant as well as O3‐sensitive genotypes and across various trophic levels. These two gases act in opposing ways, and even at low concentrations (1·5 × ambient, with ambient averaging 34–36 nL L−1 during the summer daylight hours), O3 offsets or moderates the responses induced by elevated CO2.
3
After 3 years of exposure to 560 µmol mol−1 CO2, the above‐ground volume of Aspen stands was 40% above those grown at ambient CO2, and there was no indication of a diminishing growth trend. In contrast, O3 at 1·5 × ambient completely offset the growth enhancement by CO2, both for O3‐sensitive and O3‐tolerant clones. Implications of this finding for carbon sequestration, plantations to reduce excess CO2, and global models of forest productivity and climate change are presented.
Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States of particular concern for immunosuppressed renal transplant recipients. The clinical course of ...coccidioidomycosis can be severe in immunosuppressed patients, with high rates of dissemination and mortality, and antifungal prophylaxis is routinely administered to high‐risk patients. We sought to determine the impact of coccidioidomycosis on patients who received their renal transplant at our hospital in Phoenix, Arizona. A retrospective records review of the first 205 patients who received a renal transplant between June 1999 and December 2003 identified 6 patients (3%) who had contracted coccidioidomycosis after transplantation. All six cases occurred more than 6 months after transplantation. Two of these six patients had disseminated coccidioidomycosis. Two patients, one with pulmonary infection and one with disseminated infection, died. None of the six patients with coccidioidomycosis after transplantation had identified risk factors before transplantation. No high‐risk patient who received targeted antifungal prophylaxis had a reactivation of coccidioidomycosis after transplantation. Treatment for acute rejection and induction with antithymocyte globulin did not appear to increase the risk of subsequent coccidioidomycosis.
PDF
