Diagnostic accuracy of myocardial perfusion imaging in patients evaluated for kidney transplantation:A systematic review and meta-analysis

BACKGROUND: Cardiovascular disease is the most common cause of death after kidney transplantation. Coronary artery disease (CAD) assessment is therefore mandatory in patients evaluated for transplantation. We aimed to assess the diagnostic accuracy for CAD of single-photon emission computed tomography (SPECT) compared to the standards invasive coronary angiography (ICA) and coronary computed tomography angiography (CCTA) in patients evaluated for kidney transplantation. METHODS: We performed a systematic literature search in PubMed, EMBASE, Web of Science, OvidSP (Medline), The Cochrane Library and Google Scholar. Studies investigating the diagnostic accuracy of myocardial perfusion imaging (MPI) SPECT in patients evaluated for kidney transplantation were retrieved. After a risk of bias assessment using QUADAS-2, a meta-analysis was conducted. RESULTS: Out of 1459 records, 13 MPI SPECT studies were included in the meta-analysis with a total of 1245 MPI SPECT scans. There were no studies available with CCTA as reference. Pooled sensitivity of MPI SPECT for CAD was 0.66 (95% CI 0.53 to 0.77), pooled specificity was 0.75 (95% CI 0.63 to 0.84) and the area under the curve (AUC) was 0.76. Positive likelihood ratio was 2.50 (95% CI 1.78 to 3.51) and negative likelihood ratio was 0.41 (95% CI 0.28 to 0.61). Pooled positive predictive value was 64.9% and pooled negative predictive value was 74.1%. Significant heterogeneity existed across the included studies. CONCLUSIONS: MPI SPECT had a moderate diagnostic accuracy in patients evaluated for kidney transplantation, with a high rate of false-negative findings. The use of an anatomical gold standard against a functional imaging test in the included studies is however suboptimal. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12350-021-02621-x

Reference values for low muscle mass and myosteatosis using tomographic muscle measurements in living kidney donors

Low muscle mass and myosteatosis are associated with poor clinical outcomes. Computed tomography (CT) imaging is an objective method for muscle mass and quality assessment; however consensus on cut-off values is lacking. This study assessed age-, sex-, and body mass index (BMI)-specific reference values of skeletal muscle parameters and correlated muscle mass with 24-h urinary creatinine excretion (24-h UCE). In total, 960 healthy subjects were included in this study. Muscle mass and quality were determined using axial CT slices at the vertebral level L3. The muscle area was indexed for height (skeletal muscle index [SMI]). The mean age was 53 ± 11 years, and 50% were male. The SMI reference values for low muscle mass in males were 38.8 cm2/m2 (20–29 years), 39.2 (30–39 years), 39.9 (40–49 years), 39.0 (50–59 years), 37.0 (60–69 years), and 36.8 (70–79 years). For females, these reference values were 37.5 cm2/m2 (20–29 years), 35.5 (30–39 years), 32.8 (40–49 years), 33.2 (50–59 years), 31.2 (60–69 years), and 31.5 (70–79 years). 24-h UCE and SMI were significantly correlated (r = 0.54, p &lt; 0.001) without bias between the two methods of assessing muscle mass. This study provides age-, sex-, and BMI-specific reference values for skeletal muscle parameters that will support clinical decision making.</p

Randomized multicenter trial on percutaneous versus open access in endovascular aneurysm repair (PiERO).

BACKGROUND: In endovascular valve and aortic repair, vascular access through a percutaneous approach has become the competing technique to an open surgical approach. The effect on postoperative complications and surgical site infections (SSIs) has been investigated, but randomized evidence is lacking. The objective was to investigate whether percutaneous access of the common femoral artery (CFA) with a percutaneous closure device would decrease the number of SSIs compared with open surgical access of the CFA in endovascular aneurysm repair (EVAR). METHODS: Patients with an abdominal aortic aneurysm suitable for EVAR were randomized to open or percutaneous access of the main device (MD) through the CFA. Through the contralateral side, access was obtained with the other technique than the one for which the MD was randomized. The primary outcome was number of SSIs. Secondary outcomes were wound complications, visual analog scale for pain scores, and standardized wound assessment scores during follow-up. Preoperative screening culture and groin biopsy specimens were obtained from all patients. RESULTS: Both groups contained 137 groins. SSI rate was 1.5% in the open group vs 0% in the percutaneous group. For MDs only, SSI rate was 3.1% (odds ratio, 3.3; 95% confidence interval, 0.31-347; P = .34). Wound complications were comparable in both groups. Neither nasal nor groin Staphylococcus aureus carriage had a significant effect on SSIs, Southampton Wound Assessment score, or visual analog scale score. Adjusted pain score was 0.69 lower, in favor of percutaneous access. Wound assessment was better after 2 weeks (odds ratio, 3.57; 95% confidence interval, 1.02-12.44; P = .046), also in favor of percutaneous access. CONCLUSIONS: Percutaneous access of the CFA does not reduce the number of SSIs. It does, however, reduce pain and improve wound healing with less inflammation 1 day and 2 weeks after EVAR, respectively

Intraoperative Fluid Restriction is Associated with Functional Delayed Graft Function in Living Donor Kidney Transplantation:A Retrospective Cohort Analysis

BACKGROUND: In 2016 we observed a marked increase in functional delayed graft function (fDGF) in our living donor kidney transplantation (LDKT) recipients from 8.5% in 2014 and 8.8% in 2015 to 23.0% in 2016. This increase coincided with the introduction of a goal-directed fluid therapy (GDFT) protocol in our kidney transplant recipients. Hereupon, we changed our intraoperative fluid regimen to a fixed amount of 50 mL/kg body weight (BW) and questioned whether the intraoperative fluid regimen was related to this increase in fDGF. METHODS: a retrospective cohort analysis of all donors and recipients in our LDKT program between January 2014-February 2017 (n = 275 pairs). RESULTS: Univariate analysis detected various risk factors for fDGF. Dialysis dependent recipients were more likely to develop fDGF compared to pre-emptively transplanted patients (p < 0.001). Recipients developing fDGF received less intraoperative fluid (36 (25.9-50.0) mL/kg BW vs. 47 (37.3-55.6) mL/kg BW (p = 0.007)). The GDFT protocol resulted in a reduction of intraoperative fluid administration on average by 850 mL in total volume and 21% in mL/kg BW compared to our old protocol (p < 0.001). In the unadjusted analysis, a higher intraoperative fluid volume in mL/kg BW was associated with a lower risk for the developing fDGF (OR 0.967, CI (0.941-0.993)). After adjustment for the confounders, prior dialysis and the use of intraoperative noradrenaline, the relationship of fDGF with fluid volume was still apparent (OR 0.970, CI (0.943-0.998)). CONCLUSION: Implementation of a GDFT protocol led to reduced intraoperative fluid administration in the LDKT recipients. This intraoperative fluid restriction was associated with the development of fDGF

SMASHing the LMC: A Tidally-induced Warp in the Outer LMC and a Large-scale Reddening Map

We present a study of the three-dimensional (3D) structure of the Large Magellanic Cloud (LMC) using ~2.2 million red clump (RC) stars selected from the Survey of the MAgellanic Stellar History. To correct for line-of-sight dust extinction, the intrinsic RC color and magnitude and their radial dependence are carefully measured by using internal nearly dust-free regions. These are then used to construct an accurate 2D reddening map (165 square degrees with ~10 arcmin resolution) of the LMC disk and the 3D spatial distribution of RC stars. An inclined disk model is fit to the 2D distance map yielding a best-fit inclination angle i = 25.86(+0.73,-1.39) degrees with random errors of +\-0.19 degrees and line-of-nodes position angle theta = 149.23(+6.43,-8.35) degrees with random errors of +/-0.49 degrees. These angles vary with galactic radius, indicating that the LMC disk is warped and twisted likely due to the repeated tidal interactions with the Small Magellanic Cloud (SMC). For the first time, our data reveal a significant warp in the southwestern part of the outer disk starting at rho ~ 7 degrees that departs from the defined LMC plane up to ~4 kpc toward the SMC, suggesting that it originated from a strong interaction with the SMC. In addition, the inner disk encompassing the off-centered bar appears to be tilted up to 5-15 degrees relative to the rest of the LMC disk. These findings on the outer warp and the tilted bar are consistent with the predictions from the Besla et al. simulation of a recent direct collision with the SMC.Comment: 25 pages, 15 figures, published in Ap

Validation of a Length-Adjusted Abdominal Arterial Calcium Score Method for Contrast-Enhanced CT Scans

BACKGROUND: The Agatston score on noncontrast computed tomography (CT) scans is the gold standard for calcium load determination. However, contrast-enhanced CT is commonly used for patients with atherosclerotic cardiovascular diseases (ASCVDs), such as peripheral arterial occlusive disease (PAOD) and abdominal aortic aneurysm (AAA). Currently, there is no validated method to determine calcium load in the aorta and peripheral arteries with a contrast-enhanced CT. This study validated a length-adjusted calcium score (LACS) method for contrast-enhanced CT scans.METHOD: The LACS (calcium volume in mm 3/arterial length in cm) in the abdominal aorta was calculated using four-phase liver CT scans of 30 patients treated between 2017 and 2021 at the University Medical Center Groningen (UMCG) with no aortic disease. Noncontrast CT scans were segmented with a 130 Hounsfield units (HU) threshold, and a patient-specific threshold was used for contrast-enhanced CTs. The LACS was calculated and compared from both segmentations. Secondly, the interobserver variability and the influence of slice thickness (0.75 mm vs. 2.0 mm) was determined. RESULTS: There was a high correlation between the LACS from contrast-enhanced CT scans and the LACS of noncontrast CTs ( R 2 = 0.98). A correction factor of 1.9 was established to convert the LACS derived from contrast-enhanced CT to noncontrast CT scans. LACS interobserver agreement on contrast-enhanced CT was excellent (1.0, 95% confidence interval = 1.0-1.0). The 0.75 mm CT threshold was 541 (459-625) HU compared with 500 (419-568) HU on 2 mm CTs ( p = 0.15). LACS calculated with both thresholds was not significantly different ( p = 0.63). CONCLUSION: The LACS seems to be a robust method for scoring calcium load on contrast-enhanced CT scans in arterial segments with various lengths.</p

Urinary Properdin and sC5b-9 Are Independently Associated With Increased Risk for Graft Failure in Renal Transplant Recipients

The pathophysiology of late kidney-allograft failure remains complex and poorly understood. Activation of filtered or locally produced complement may contribute to the progression of renal failure through tubular C5b-9 formation. This study aimed to determine urinary properdin and sC5b-9 excretion and assess their association with long-term outcome in renal transplant recipients (RTR). Methods: We measured urinary properdin and soluble C5b-9 in a well-defined cross-sectional cohort of RTR. Urinary specimens were taken from a morning urine portion, and properdin and sC5b-9 were measured using an enzyme-linked-immunosorbent assay (ELISA). Cox proportional hazard regression analyses were used to investigate prospective associations with death-censored graft failure. Results: We included 639 stable RTR at a median [interquartile range] 5.3 (1.8-12.2) years after transplantation. Urinary properdin and sC5b-9 excretion were detectable in 161 (27%) and 102 (17%) RTR, respectively, with a median properdin level of 27.6 (8.6-68.1) ng/mL and a median sC5b-9 level of 5.1 (2.8-12.8) ng/mL. In multivariable-adjusted Cox regression analyses, including adjustment for proteinuria, urinary properdin (HR, 1.12; 95% CI 1.02-1.28; P = 0.008) and sC5b-9 excretion (HR, 1.34; 95% CI 1.10-1.63; P = 0.003) were associated with an increased risk of graft failure. If both urinary properdin and sC5b-9 were detectable, the risk of graft failure was further increased (HR, 3.12; 95% CI 1.69-5.77; P < 0.001). Conclusions: Our findings point toward a potential role for urinary complement activation in the pathogenesis of chronic allograft failure. Urinary properdin and sC5b-9 might be useful biomarkers for complement activation and chronic kidney allograft deterioration, suggesting a potential role for an alternative pathway blockade in RTR

Renal Endothelial Cytotoxicity Assay to Diagnose and Monitor Renal Transplant Recipients for Anti-Endothelial Antibodies

Tissue-specific nonhuman leukocyte antigen (HLA) antigens can play crucial roles in allograft immunity and have been shown to trigger humoral responses leading to rejection of HLA-matched kidney allografts. Interest in the role of endothelial-specific antigens has grown over the past years, and several case reports have been described in which antibodies reacting with endothelial cells (ECs) are associated with rejection. Such antibodies escape the detection in conventional crossmatch tests as they do not react with lymphocytes. However, due to the heterogeneity of endothelial cells from different vascular beds, it remains difficult to draw organ-specific conclusions from studies describing endothelial crossmatch assays. We present a case of a 69-year-old male patient whose kidney allograft was rejected as hyperacute, despite the absence of pretransplant HLA-specific antibodies. To place findings from previous studies in a kidney-related context, we performed crossmatch assays with primary renal endothelial cells. The patient's serum was reactive with primary renal ECs, demonstrated by antibody binding and complement-dependent cytotoxicity. Antibodies from this patient did not react with lymphocytes nor were HLA donor-specific antibodies (DSAs) found. Two years later, the patient successfully received a second kidney transplant after treatment with rituximab and plasmapheresis before and after transplantation. We demonstrated that the removal of antibodies against non-HLA EC-specific molecules can be monitored using a primary renal EC crossmatch test, possibly contributing to a successful transplantation outcome