Development of a Multiparametric Renal CT Algorithm for Diagnosis of Clear Cell Renal Cell Carcinoma Among Small (≤ 4 cm) Solid Renal Masses.

BACKGROUND. The MRI clear cell likelihood score predicts the likelihood that a renal mass is clear cell renal cell carcinoma (ccRCC). A CT-based algorithm has not yet been established. OBJECTIVE. The purpose of our study was to develop and evaluate a CT-based algorithm for diagnosing ccRCC among small (≤ 4 cm) solid renal masses. METHODS. This retrospective study included 148 patients (73 men, 75 women; mean age, 58 ± 12 [SD] years) with 148 small (≤ 4 cm) solid (> 25% enhancing tissue) renal masses that underwent renal mass CT (unenhanced, corticomedullary, and nephrographic phases) before resection between January 2016 and December 2019. Two radiologists independently evaluated CT examinations and recorded calcification, mass attenuation in all phases, mass-to-cortex corticomedullary attenuation ratio, and heterogeneity score (score on a 5-point Likert scale, assessed in corticomedullary phase). Features associated with ccRCC were identified by multivariable logistic regression analysis and then used to create a five-tiered CT score for diagnosing ccRCC. RESULTS. The masses comprised 53% (78/148) ccRCC and 47% (70/148) other histologic diagnoses. The mass-to-cortex corticomedullary attenuation ratio was higher for ccRCC than for other diagnoses (reader 1: 0.84 ± 0.68 vs 0.68 ± 0.65, p = .02; reader 2: 0.75 ± 0.29 vs 0.59 ± 0.25, p = .02). The heterogeneity score was higher for ccRCC than other diagnoses (reader 1: 4.0 ± 1.1 vs 1.5 ± 1.6, p < .001; reader 2: 4.4 ± 0.9 vs 3.3 ± 1.5, p < .001). Other features showed no difference. A five-tiered diagnostic algorithm including the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score had interobserver agreement of 0.71 (weighted κ) and achieved an AUC for diagnosing ccRCC of 0.75 (95% CI, 0.68-0.82) for reader 1 and 0.72 (95% CI, 0.66-0.82) for reader 2. A CT score of 4 or greater achieved sensitivity, specificity, and PPV of 71% (95% CI, 59-80%), 79% (95% CI, 67-87%), and 79% (95% CI, 67-87%) for reader 1 and 42% (95% CI, 31-54%), 81% (95% CI, 70-90%), and 72% (95% CI, 56-84%) for reader 2. A CT score of 2 or less had NPV of 85% (95% CI, 69-95%) for reader 1 and 88% (95% CI, 69-97%) for reader 2. CONCLUSION. A five-tiered renal CT algorithm, including the mass-to-cortex corticomedullary attenuation ratio and heterogeneity score, had substantial interobserver agreement, moderate AUC and PPV, and high NPV for diagnosing ccRCC. CLINICAL IMPACT. The CT algorithm, if validated, may represent a useful clinical tool for diagnosing ccRCC.

Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis.

Background Gadoxetic acid is classified by the American College of Radiology as a group III gadolinium-based contrast agent (GBCA), which indicates that there are limited data regarding nephrogenic systemic fibrosis (NSF) risk, but there are few if any unconfounded cases of NSF. Purpose To perform a systematic review and meta-analysis of gadoxetic acid adverse events, including immediate hypersensitivity reactions, NSF, and intracranial gadolinium retention. Materials and Methods Original research studies, case series, and case reports that reported adverse events in patients undergoing gadoxetic acid-enhanced MRI were searched in MEDLINE (1946-2019), Embase (1947-2019), CENTRAL (March 2019), and Scopus (1946-2019). The study protocol was registered at Prospero (number 162811). Risk of bias was evaluated by using Quality Assessment of Diagnostic Accuracy Studies-2, or QUADAS-2. Meta-analysis of proportions was performed by using random-effects modeling. Upper bound of 95% confidence interval (CI) for risk of NSF was determined. Results Seventy-one studies underwent full-text review. From 17 studies reporting 14 850 administrations, hypersensitivity reactions occurred in 0.3% (31 of 14 850; 95% CI: 0.2%, 0.4%) with zero deaths. From four studies reporting 106 administrations in patients with stage 4 or 5 chronic kidney disease or undergoing dialysis, the upper bound 95% CI for the risk of NSF was 2.8%. Five studies evaluating intracranial retention of gadolinium after gadoxetic acid administration were at high risk of bias. Conclusion Gadoxetic acid had a similar safety profile to American College of Radiology group 2 gadolinium-based contrast agents for hypersensitivity reactions and nephrogenic systemic fibrosis (NSF) but had lower confidence for risk of NSF because of fewer administrations in patients with severe kidney impairment. There is incomplete information documenting intracranial gadolinium retention in patients administered gadoxetic acid. © RSNA, 2020 Online supplemental material is available for this article.

Updated Clinical Practice Guideline on Use of Gadolinium-Based Contrast Agents in Kidney Disease Issued by the Canadian Association of Radiologists.

In 2017, the Canadian Association of Radiologists issued a clinical practice guideline (CPG) regarding the use of gadolinium-based contrast agents (GBCAs) in patients with acute kidney injury (AKI), chronic kidney disease (CKD), or on dialysis due to mounting evidence indicating that nephrogenic systemic fibrosis (NSF) occurs with extreme rarity or not at all when using Group II GBCAs or the Group III GBCA gadoxetic acid (compared to first generation Group I linear GBCAs). One of the goals of the work group was to re-evaluate the CPG after 24 months to determine the effect of more liberal use of GBCA on reported cases of NSF in patients with AKI, CKD Stage 4 or 5 (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2), or those that are dialysis-dependent. A comprehensive review of the literature was conducted by a subcommittee of the initial CPG panel between the dates of January 1, 2017-December 31, 2018 to identify new unconfounded cases of NSF linked to Group II or Group III GBCAs and an updated CPG developed. To our knowledge, when using a Group II or Group III GBCA between 2017-2018, only a single unconfounded case report of a fibrosing dermopathy has been reported in a patient who received gadobenate dimeglumine with Stage 2 CKD. No other unconfounded cases of NSF have been reported with Group II or III agents in during this timeframe. The subcommittee concluded that the main recommendations from the 2017 CPG should remain unaltered, but agreed that screening for renal disease in the outpatient setting is no longer justifiable, cost-effective or recommended. Patients on hemodialysis (HD) should, however, be identified prior to GBCA administration to arrange timely HD to optimize gadolinium clearance, although there remains no evidence that HD reduces the risk of NSF. When administering Group II or III GBCAs to patients with AKI, on dialysis or with severe CKD, informed consent relating to NSF is also no longer explicitly recommended.

Generic immunosuppression in solid organ transplantation: systematic review and meta-analysis.

OBJECTIVE: To compare the clinical efficacy and bioequivalence of generic immunosuppressive drugs in patients with solid organ transplants. DESIGN: Systematic review and meta-analysis of all studies comparing generic with innovator immunosuppressive drugs. DATA SOURCES: Medline and Embase from 1980 to September 2014. REVIEW METHODS: A literature search was performed for all studies comparing a generic to an innovator immunosuppressive drug in solid organ transplantation. Two reviewers independently extracted data and assessed quality of studies. Meta-analyses of prespecified outcomes were performed when deemed appropriate. Outcomes included patient survival, allograft survival, acute rejection, adverse events and bioequivalence. RESULTS: 1679 citations were screened, of which 50 studies met eligibility criteria (17 randomized trials, 15 non-randomized interventional studies, and 18 observational studies). Generics were compared with Neoral (cyclosporine) (32 studies), Prograf (tacrolimus) (12 studies), and Cellcept (mycophenolate mofetil) (six studies). Pooled analysis of randomized controlled trials in patients with kidney transplants that reported bioequivalence criteria showed that Neoral (two studies) and Prograf (three studies) were not bioequivalent with generic preparations according to criteria of the European Medicines Agency. The single Cellcept trial also did not meet bioequivalence. Acute rejection was rare but did not differ between groups. For Neoral, the pooled Peto odds ratio was 1.23 (95% confidence interval 0.64 to 2.36) for kidney randomized controlled trials and 0.66 (0.40 to 1.08) for observational studies. For kidney observational studies, the pooled Peto odds ratios were 0.98 (0.37 to 2.60) for Prograf and 0.49 (0.09 to 2.56) for Cellcept. Meta-analyses for non-renal solid organ transplants were not performed because of a lack of data.There were insufficient data reported on patient or graft survival. Pooling of results was limited by inconsistent study methods and reporting of outcomes. Many studies did not report standard criteria used to determine bioequivalence. While rates of acute rejection seemed similar and were relatively rare, few studies were designed to properly compare clinical outcomes. Most studies had short follow-up times and included stable patients without a history of rejection. CONCLUSIONS: High quality data showing bioequivalence and clinical efficacy of generic immunosuppressive drugs in patients with transplants are lacking. Given the serious consequences of rejection and allograft failure, well designed studies on bioequivalence and safety of generic immunosuppression in transplant recipients are needed.

Mineral metabolism and cortical volumetric bone mineral density in childhood chronic kidney disease.

CONTEXT: The relationships among cortical volumetric bone mineral density (CortBMD) and comprehensive measures of mineral metabolism have not been addressed in chronic kidney disease (CKD). OBJECTIVE: The aim of the study was to identify the determinants of CortBMD in childhood CKD. A secondary objective was to assess whether CortBMD was associated with subsequent fracture. DESIGN AND PARTICIPANTS: This prospective cohort study included 171 children, adolescents, and young adults (aged 5-21 years) with CKD stages 2-5D at enrollment and 89 1 year later. OUTCOMES: Serum measures included vitamin D [25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D], vitamin D-binding protein, intact PTH, fibroblast growth factor 23, calcium, and phosphorus. Tibia quantitative computed tomography measures of CortBMD were expressed as sex-, race-, and age-specific Z-scores based on 675 controls. Multivariable linear regression identified the independent correlates of CortBMD Z-scores and the change in CortBMD Z-scores. RESULTS: Lower calcium (ß = .31/1 mg/dL, P = .01) and 25(OH)D (ß = .18/10 ng/mL, P = .04) and higher PTH (ß = -.02/10%, P = .002) and 1,25(OH)2D (ß = -.07/10%, P < .001) were independently associated with lower CortBMD Z-scores at baseline. The correlations of total, free, and bioavailable 25(OH)D with CortBMD did not differ. Higher baseline 1,25(OH)2D (P < .05) and greater increases in PTH (P < .001) were associated with greater declines in CortBMD Z-scores. Greater increases in calcium concentrations were associated with greater increases in CortBMD Z-scores in growing children (interaction P = .009). The hazard ratio for fracture was 1.75 (95% confidence interval 1.15-2.67; P = .009) per SD lower baseline CortBMD. CONCLUSIONS: Greater PTH and 1,25(OH)2D and lower calcium concentrations were independently associated with baseline and progressive cortical deficits in childhood CKD. Lower CortBMD Z-score was associated with increased fracture risk.

Xenophilus aerolatus Peritonitis in a six-year-old boy on maintenance eritoneal dialysis.

Peritonitis remains a significant complication of peritoneal dialysis (PD). Although most patients can be treated successfully with antibiotics and continue PD, the poorest outcomes are noted in patients with peritonitis secondary to gram-negative organisms, which may lead to temporary or permanent technique failure. Biofilm formation may result in. failure of appropriate antibiotic therapy to eradicate infection, necessitating catheter replacement or a switch to hemodialysis. Here, we report the first case of gram-negative peritonitis caused by Xenophilus aerolatus in a 6-year-old boy on continuous cycling PD. This case highlights the importance of close monitoring of clinical response and of collaboration with the microbiologist and microbiology lab in the identification of unusual organisms, their antimicrobial susceptibilities, and their expected characteristics.