SummaryBackground and objectives Autosomal dominant polycystic kidney disease (ADPKD) is characterized by increased total kidney volume (TKV) and renal failure. This study aimed to determine if height-adjusted TKV (htTKV) predicts the onset of renal insufficiency.Design, setting, participants, & measurements This prospective, observational, longitudinal, multicenter study included 241 adults with ADPKD and preserved renal function. Magnetic resonance imaging and iothalamate clearance were used to measure htTKV and GFR, respectively. The association between baseline htTKV and the attainment of stage 3 CKD (GFR ,60 ml/min per 1.73 m 2 ) during follow-up was determined.Results After a mean follow-up of 7.9 years, stage 3 CKD was attained in 30.7% of the enrollees. Using baseline htTKV, negative correlations with GFR increased from 20.22 at baseline to 20.65 at year 8. In multivariable analysis, a baseline htTKV increase of 100 cc/m significantly predicted the development of CKD within 8 years with an odds ratio of 1.48 (95% confidence interval: 1.29, 1.70). In receiver operator characteristic curve analysis, baseline htTKV of 600 cc/m most accurately defined the risk of developing stage 3 CKD within 8 years with an area under the curve of 0.84 (95% confidence interval: 0.79, 0.90). htTKV was a better predictor than baseline age, serum creatinine, BUN, urinary albumin, or monocyte chemotactic protein-1 excretion (P,0.05).Conclusions Baseline htTKV $600 cc/m predicted the risk of developing renal insufficiency in ADPKD patients at high risk for renal disease progression within 8 years of follow-up, qualifying htTKV as a prognostic biomarker in ADPKD.

HISTO is an accurate, reproducible MR spectroscopic sequence for quantifying hepatic lipid noninvasively. Evidence has shown this method to be feasible in vivo for clinical use.

SummaryBackground and objectives The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) was created to identify markers of disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD).Design, setting, participants, & measurements Linear mixed models were utilized to model effects of baseline parameters on changes in natural-log (ln)-transformed total kidney volume (TKV) and iothalamate clearance (GFR) across time in CRISP participants (creatinine clearance at entry Ͼ70 ml/min). Stepwise selection was used to obtain a final main effect model.Results TKV increased from year to year, whereas GFR uncorrected for body surface area (BSA) decreased only at year 6. Higher lnTKV and urine sodium excretion (U Na V), lower serum HDL-cholesterol, and younger age at baseline associated with greater lnTKV growth from baseline to year 3 and to year 6. Higher lnTKV at baseline associated with greater GFR decline from year 1 to year 3 and to year 6. Higher BSA and 24-hour urine osmolality at baseline associated with greater GFR decline from year 1 to year 6. Higher U Na V and lower serum HDL-cholesterol at baseline associated with greater GFR decline from year 1 to year 6 by univariate analysis only. Associations seen during year 1 to year 6 (not seen during year 1 to year 3) reflect the time lag between structural and functional disease progression.Conclusions Serum HDL-cholesterol, U Na V, and 24-hour urine osmolality likely affect ADPKD progression. To what extent their modification may influence the clinical course of ADPKD remains to be determined.

The purpose of this study was to compare dual-phase spiral computed tomography (CT) and magnetic resonance imaging (MRI) using dynamic gadolinium enhancement for liver lesion detection and characterization. Twenty-two consecutive patients underwent dual-phase spiral CT and MRI for the evaluation of focal liver disease within a 1-month period. Spiral CT and MR images were interpreted prospectively, in a blinded fashion by separate, individual, experienced investigators, to determine lesion detection and characterization. Liver lesions were confirmed by surgery and pathology in 6 patients, and by clinical and imaging follow-up in the other 16 patients. Pathological correlation of a primary extrahepatic malignancy was available in 5 of the 16 patients who had metastatic liver disease. Spiral CT and MRI detected 53 and 63 lesions, and characterized 39 and 62 true positive lesions, respectively. A kappa statistic test was applied to assess agreement between MR and CT results. MR versus CT for lesion detection resulted in a kappa statistic of 0.54 (95% confidence interval), indicating moderate agreement, and 0.32 (95% confidence interval) for lesion characterization, indicating only slight agreement. More lesions were detected on MR images than CT images in 6 (27%) patients, with lesions detected only on MR images in 4 (18%) patients. More lesions were characterized on MR images in 9 (41%) patients. In 9 patients with a discrepancy between MR and CT findings, the MR images added information considered significant to patient management in all 9 cases. MRI was moderately superior to dual-phase spiral CT for lesion detection, and was markedly superior for lesion characterization, with these differences having clinical significance. J. Index terms: liver; MR; CT; contrast agents; focal liver lesion DUAL-PHASE SPIRAL CT (1,2) and MRI, using dynamic gadolinium administration (3-10), are used to evaluate focal liver disease. Despite the common occurrence of focal liver lesions, and the importance of determining the most accurate method to evaluate focal liver disease, few studies have compared dual-phase spiral CT and MRI, using various contrast agents, for the detection and characterization of liver lesions (11-13). Previous studies from our center compared MRI to dynamic contrast-enhanced CT or single phase spiral CT for liver lesion detection and characterization (5,6). The purpose of the current study was to compare dual-phase spiral CT and MRI, using dynamic gadolinium administration, for the detection and characterization of focal liver lesions. MATERIALS AND METHODS PatientsTwenty-two consecutive patients (11 males, ages 28 -77 years; 11 females, ages 44 -86 years) with suspected liver lesions, who underwent both spiral CT and MRI within a period of less than 1 month, were included in this study. No patients were excluded from the study due to technical, patient, or other factors. No other specific selection criteria were used, and all paired studies were performed at the request of referring physicians. Dual-phase sp...

RationaleThe SARS-CoV-2/COVID-19 pandemic has highlighted the serious unmet need for effective therapies that reduce ARDS mortality. We explored whether extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a ligand for Toll-like receptor 4 and a master regulator of innate immunity and inflammation, is a potential ARDS therapeutic target.MethodsWild type C57BL/6J or endothelial cell (EC)-cNAMPT−/− knockout mice (targeted EC NAMPT deletion) were exposed to either a lipopolysaccharide (LPS)-induced (“one-hit”) or a combined LPS/ventilator (“two-hit”)-induced acute inflammatory lung injury model. A NAMPT-specific mAb imaging probe (99mTc-ProNamptorTM) was used to detect NAMPT expression in lung tissues. Either an eNAMPT-neutralising goat polyclonal antibody (pAb) or a humanised monoclonal antibody (ALT-100 mAb) were utilised in vitro and in vivo.ResultsImmunohistochemical, biochemical, and imaging studies validated time-dependent increases in NAMPT lung tissue expression in both preclinical ARDS models. Intravenous delivery of either eNAMPT-neutralising pAb/mAb significantly attenuated inflammatory lung injury (H & E staining, BAL protein, BAL PMNs, plasma IL-6) in both preclinical models. In vitro human lung EC studies demonstrated eNAMPT-neutralising antibodies (pAb, mAb) to strongly abrogate eNAMPT-induced TLR4 pathway activation and EC barrier disruption. In vivo studies in wild type and EC-cNAMPT−/− mice confirmed a highly significant contribution of EC-derived NAMPT to the severity of inflammatory lung injury in both preclinical ARDS models.ConclusionsThese findings highlight both the role of EC-derived eNAMPT and the potential for biologic targeting of the eNAMPT/TLR4 inflammatory pathway. In combination with predictive eNAMPT biomarker and NAMPT genotyping assays, this offers the opportunity to identify high-risk ARDS subjects for delivery of personalised medicine.