Prospective Comparison of Contrast-Enhanced Ultrasound and Magnetic Resonance Imaging to Computer Tomography for the Evaluation of Complex Cystic Renal Lesions.

OBJECTIVE: To prospectively evaluate the diagnostic accuracy of contrast enhanced ultrasound (CEUS) and MRI compared to computed tomography (CT) as the current gold standard for the characterization of cystic renal lesions using the Bosniak classification. METHODS: Between July 2014 and October 2017 we prospectively enrolled patients with cystic renal lesions. Based on the Bosniak classification of complex renal lesions (≥BII-F) we evaluated the accuracy of observed agreement by Cohen's Kappa coefficient and calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) between the three imaging modalities CT, MRI and CEUS. RESULTS: We evaluated 65 cystic renal lesions in 48 patients (median age 63 years, range 36-91 years; 18 females, 30 males). According to CT 29 (47%) of the cystic renal lesions were classified as complex. The agreement between CEUS and CT in the classification of complex cystic lesions was fair (agreement 50.8%, Kappa 0.31), and was excellent between MRI and CT (agreement 93.9%, Kappa 0.88). Compared to CT, CEUS and MRI had a sensitivity of 100% and 96.6%, a specificity of 33.3% and 91.7%, a PPV of 54.7% and 90.3%, and a NPV of 100% and 97.1% with an accuracy of 63.1% and 93.8% respectively. CONCLUSION: CEUS has an excellent sensitivity and NPV and represents a promising non-invasive screening tool for renal cystic lesions. The classification of complex renal cysts based on MRI and CT scans correlated closely.

Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with severe cardiovascular complications. The T50 score is a novel functional blood test quantifying calcification propensity in serum. High calcification propensity (or low T50) is a strong and independent determinant of all-cause mortality in various patient populations. METHODS: A total of 168 patients with ≥ 4 American College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus erythematosus Cohort Study (SSCS) were included in this analysis. Serum calcification propensity was assessed using time-resolved nephelometry. RESULTS: The cohort mainly consisted of female (85%), middle-aged (43±14 years) Caucasians (77%). The major determinants of T50 levels included hemoglobin, serum creatinine and serum protein levels explaining 43% of the variation at baseline. Integrating disease activity (SELENA-SLEDAI) into this multivariate model revealed a significant association between disease activity and T50 levels. In a subgroup analysis considering only patients with active disease (SELENA-SLEDAI score ≥4) we found a negative association between T50 and SELENA-SLEDAI score at baseline (Spearman's rho -0.233, P = 0.02). CONCLUSIONS: Disease activity and T50 are closely associated. Moreover, T50 levels identify a subgroup of SLE patients with ongoing systemic inflammation as mirrored by increased disease activity. T50 could be a promising biomarker reflecting SLE disease activity and might offer an earlier detection tool for high-risk patients.

Emergency medicine in the extreme geriatric era: A retrospective analysis of patients aged in their mid 90s and older in the emergency department.

AIM: In the coming years, older individuals will comprise an increasing share of emergency department (ED) admissions, due to the unprecedented and continuing demographic changes. The primary aim of the present study was to identify causes and risk factors for ED admission and hospitalizations in the oldest old. METHODS: We analyzed data of consecutive patients aged in their mid 90s and older (aged ≥94 years) admitted to the ED department of the University Hospital of Bern, Bern, Switzerland, between 2000 and 2010. Using multivariate logistic regression, we explored relevant demographic and clinical characteristics of patients visiting the ED, in association with hospitalization and fractures. RESULTS: A total of 352 ED admissions occurred during the study period. The majority of patients (85%) were admitted from home, and most (63%) admissions resulted in hospitalization. Hospital admissions were frequently related to injuries from falls (42%). Risk factors for hospitalization were fractures, the number of comorbidities (measured by the Charlson Comorbidity Index) and hypertension. Major risk factors for fractures were female sex, benzodiazepine use and the diagnosis of dementia. CONCLUSIONS: Most ED visits of older adults aged in their mid 90s and older were due to falls and fractures, and resulted in hospitalization. The present findings clearly emphasize the need for further investigations of drug prescription patterns and fracture prevention in such patients. Geriatr Gerontol Int 2018; 18: 415-420.

C-terminal fragment of agrin (CAF) levels predict acute kidney injury after acute myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction are at high risk for acute kidney injury. Novel biomarkers that can predict acute kidney injury in AMI may allow timely interventions. C-terminal fragment of agrin (CAF), a proteoglycan of the glomerular and tubular basement membrane, have been recently associated with rapid renal function deterioration and proximal tubular dysfunction. It is unknown whether elevated CAF levels may serve as a novel AKI biomarker in patients presenting with AMI. METHODS: In 436 persons enrolled in a multicenter prospective observational cohort study of patients with acute myocardial infarction, we measured plasma and urine levels of several kidney injury biomarkers including CAF, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and cystatin-C.The relationship between biomarker levels at baseline and the development of AKI and long-term mortality were analyzed after adjustment for demographic and clinical variables. RESULTS: AKI incidence was up to 15% during hospitalization. The predictive accuracy for AKI of urinary CAF was similar to NGAL and superior to other tested kidney injury biomarkers. In a multivariate model that included all possible confounding variables only urinary CAF continued to be an independent marker for AKI (OR 1.35 95%CI 1.05 -1.74). During the 2 years follow-up, only plasma CAF levels remained a significant independent predictor of mortality (OR 2.5 95%CI 1.02-6.2; P = 0.04). CONCLUSIONS: Elevated CAF levels are associated with AKI in patients with acute myocardial infarction. Our study provides preliminary evidence that CAF levels may predict AKI and mortality after AMI in low risk patients with relative preserved kidney function at baseline.

Blood Calcification Propensity, Cardiovascular Events, and Survival in Patients Receiving Hemodialysis in the EVOLVE Trial.

BACKGROUND AND OBJECTIVES: Patients receiving hemodialysis are at risk of cardiovascular events. A novel blood test (T50 test) determines the individual calcification propensity of blood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: T50 was determined in 2785 baseline serum samples of patients receiving hemodialysis enrolled in the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) trial and the T50 results were related to patient outcomes. RESULTS: Serum albumin, bicarbonate, HDL cholesterol, and creatinine were the main factors positively/directly and phosphate was the main factor negatively/inversely associated with T50. The primary composite end point (all-cause mortality, myocardial infarction [MI], hospitalization for unstable angina, heart failure, or peripheral vascular event [PVE]) was reached in 1350 patients after a median follow-up time of 619 days. After adjustments for confounding, a lower T50 was independently associated with a higher risk of the primary composite end point as a continuous measure (hazard ratio [HR] per 1 SD lower T50, 1.15; 95% confidence interval [95% CI], 1.08 to 1.22; P<0.001). Furthermore, lower T50 was associated with a higher risk in all-cause mortality (HR per 1 SD lower T50, 1.10; 95% CI, 1.02 to 1.17; P=0.001), MI (HR per 1 SD lower T50, 1.38; 95% CI, 1.19 to 1.60; P<0.001), and PVE (HR per 1 SD lower T50, 1.22; 95% CI, 1.05 to 1.42; P=0.01). T50 improved risk prediction (integrated discrimination improvement and net reclassification improvement, P<0.001 and P=0.001) of the primary composite end point. CONCLUSIONS: Blood calcification propensity was independently associated with the primary composite end point, all-cause mortality, MI, and PVE in the EVOLVE study and improved risk prediction. Prospective trials should clarify whether T50-guided therapies improve outcomes.

Calcification Propensity and Survival among Renal Transplant Recipients.

Calciprotein particle maturation time (T50) in serum is a novel measure of individual blood calcification propensity. To determine the clinical relevance of T50 in renal transplantation, baseline serum T50 was measured in a longitudinal cohort of 699 stable renal transplant recipients and the associations of T50 with mortality and graft failure were analyzed over a median follow-up of 3.1 years. Predictive value of T50 was assessed for patient survival with reference to traditional (Framingham) risk factors and the calcium-phosphate product. Serum magnesium, bicarbonate, albumin, and phosphate levels were the main determinants of T50, which was independent of renal function and dialysis vintage before transplant. During follow-up, 81 (12%) patients died, of which 38 (47%) died from cardiovascular causes. Furthermore, 45 (6%) patients developed graft failure. In fully adjusted models, lower T50 values were independently associated with increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval, 1.11 to 1.85; P=0.006 per SD decrease) and increased cardiovascular mortality (hazard ratio, 1.55; 95% confidence interval, 1.04 to 2.29; P=0.03 per SD decrease). In addition to age, sex, and eGFR, T50 improved prognostication for all-cause mortality, whereas traditional risk factors or calcium-phosphate product did not. Lower T50 was also associated with increased graft failure risk. The associations of T50 with mortality and graft failure were confirmed in an independent replication cohort. In conclusion, reduced serum T50 was associated with increased risk of all-cause mortality, cardiovascular mortality, and graft failure and, of all tested parameters, displayed the strongest association with all-cause mortality in these transplant recipients.

Radiometrical, hormonal and biological correlates of skeletal growth in the female rat from birth to senescence.

OBJECTIVE: We investigated the skeletal growth profile of female rats from birth to senescence (100weeks) on the basis of sequential radiometrical, hormonal and biochemical parameters. DESIGN: Weaning rats entered the study which was divided into two sections: a) sequential measurements of vertebral and tibial growths and bone mineral density (BMD), estimation of mineral content of the entire skeleton (BMC) and chemical analysis of vertebral Ca; and b) determination of basal and pulsatile growth hormone (rGH), insulin-like growth hormone (IGF-I), estradiol (E2), parathyroid hormone (PTH), osteocalcin (OC) and urinary d-pyridinoline (dp) throughout the experimental period. RESULTS: Vertebral and tibial growths ceased at week 25 whereas BMD and BMC as well as total vertebral Ca exhibited a peak bone mass at week 40. rGH pulsatile profiles were significantly higher in younger animals coinciding with the period of active growth and IGF-I peaked at 7weeks, slowly declining thereafter and stabilizing after week 60. OC and dp closely paralleled IGF-I coinciding with the period of enhanced skeletal growth, remaining thereafter in the low range indicative of reduced bone turnover. E2 increased during reproductive life but the lower values subsequently recorded were still in the physiological range, strongly suggesting a protective role of this steroid on bone remodeling. PTH followed a similar profile to E2, but the significance of this after completion of growth remains unclear. CONCLUSIONS: Mechanisms governing skeletal growth in the female rat appear similar to those in humans. Bone progression and attainment of peak bone mass are under simultaneous control of rGH, IGF-I and calciotropic hormones and are modulated by E2. This steroid seems to protect the skeleton from resorption before senescence whereas the role of PTH in this context remains uncertain.

[Scores and stages in nephrology]. / Stadien und Klassifikationen in der Nephrologie.

In this article we review the most relevant acronyms, scores and classifications in the fields of nephrology and urology, including the newest definitions of acute kidney injury and chronic kidney diseases. We will also present a short overview of the histopathological Lupus nephritis classification, the renal cysts Bosniak classification and the vesicoureteral reflux grading.

Hypercalcemia in the ED: prevalence, etiology, and outcome.

PURPOSES: The aim of the study was to describe the prevalence, demographic, and clinical characteristics and etiologies of hypercalcemia in emergency department patients. BASIC PROCEDURES: In this retrospective cross-sectional descriptive study, all patients admitted between April 1, 2008, and March 31, 2011, to the emergency department of Inselspital, University Hospital Bern, were screened for the presence of hypercalcemia, defined as a serum calcium exceeding 2.55 mmol/L after correction for serum albumin. Demographic, laboratory, and outcome data were gathered. A detailed medical record review was performed to identify causes of hypercalcemia. MAIN FINDINGS: During the study period, 14 984 patients (19% of all admitted patients) received a measurement of serum calcium. Of these, 116 patients (0.7%) presented with hypercalcemia. Median serum calcium was 2.72 mmol/L (first quartile, 2.64; third quartile, 2.88), with 4.3 mmol/L being the maximum serum calcium value observed. Underlying malignancy in 44% of patients and hyperparathyroidism in 20% (12% secondary and 8% primary) were the leading causes of hypercalcemia. Twenty-six percent of patients presented with symptomatic hypercalcemia. Weakness was the most common symptom of hypercalcemia, followed by nausea and disorientation. PRINCIPAL CONCLUSIONS: Hypercalcemia is a rare but harmful electrolyte disorder in emergency department patients. Unspecific symptoms such as a change in mental state, weakness, or gastrointestinal symptoms should prompt physicians to order serum calcium measurements, at least in patients with known malignancy or renal insufficiency.

Perilipin-1 in hemodialyzed patients: association with history of coronary heart disease and lipid profile.

Perilipin-1 surrounds lipid droplets in both adipocytes and in atheroma plaque foam cells and controls access of lipases to the lipid core. In hemodialysis (HD) patients, dyslipidemia, malnutrition, inflammation and atherosclerosis are common. Thirty-six HD patients and 28 healthy volunteers were enrolled into the study. Ten HD patients suffered from coronary heart disease (CHD). Perilipin-1, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), body mass index, albumin, geriatric nutritional risk index, normalized protein catabolic rate, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured. Perilipin-1 did not differ between HD patients and healthy volunteers. IL-6 and TNF-α were higher in HD patients. The evaluated nutritional markers and the markers of inflammation did not differ between HD patients with high perilipin-1 levels and HD patients with low perilipin-1 levels. Regarding the lipid profile, only HDL-C differed between HD patients with high perilipin-1 levels and HD patients with low perilipin-1 levels, and it was higher in the first subgroup. Perilipin-1 was significantly higher in HD patients without CHD. Perilipin-1 is detectable in the serum of HD patients and it is associated with increased HDL-C and decreased incidence of CHD.

Simultaneous clinical resolution of focal segmental glomerulosclerosis associated with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab.

BACKGROUND: Although renal involvement in advanced haematological malignancies is common, glomerulonephritis associated with lymphoproliferative disorders is rare, and the related pathogenetic mechanisms are still poorly understood. We present a rare case of chronic lymphocytic leukaemia(CLL)-associated focal segmental glomerulosclerosis with nephrotic-range proteinuria. CASE PRESENTATION: A 53-year-old Caucasian man, previously healthy, with no history of hypertension, alcohol use or smoking presented with rapid weight gain, massive peripheral oedema, and hypertension. Laboratory findings included a white blood cell count of 49,800 cells/mm3 with an absolute lymphocyte count of 47,000 cells/mm3, serum albumin of 2.3 g/dL, urea 65 mg/dL, and creatinine 1.5 mg/dL. A 24-hour urine collection contained 7.1 g protein and significant haematuria. A peripheral blood smear showed mature lymphocytosis and smudge cells. Diagnostic imaging showed mild paraaortic lymphadenopathy with no renal abnormalities. Bone marrow aspiration and trephine biopsy showed diffuse and focal infiltration with B-CLL lymphocytes. Percutaneous renal biopsy revealed total sclerosis in 3/21(14%) of the glomeruli and focal and segmental solidification and sclerosis in 4/21 (19%) glomeruli. A regimen of fludarabine, cyclophosphamide and rituximab was successful in inducing remission of the CLL and clinical resolution of the nephritic-range proteinuria. CONCLUSIONS: A multidisciplinary approach to monitor both the malignancy and the glomerular lesions is crucial for the optimal management of paraneoplastic glomerulonephritis. Although chemotherapy with fludarabine, cyclophosphamide and rituximab successfully treated CLL-associated nephrotic syndrome in our patient, further studies are required to confirm efficacy in this setting.