Predictors of mortality in a cohort of intensive care unit patients with acute renal failure receiving continuous renal replacement therapy

BACKGROUND: Despite the frequent use of continuous renal replacement therapy (CRRT) in the management of acute renal failure (ARF) in the critically ill, predictors of mortality remain unclear. METHODS: A registry of all patients initiated on CRRT at a single institution was assembled over an 18-month period, and a subsequent cross-sectional analysis of selected variables was conducted for associations with mortality. Predictors evaluated were age, gender, diagnosis of sepsis, Apache II score, days between ARF diagnosis and initiation of CRRT, creatinine at initiation of CRRT, change in creatinine from baseline and admission to initiation of CRRT, setting of ARF, and prescribed CRRT dose. The principal outcome was mortality at 30 days. RESULTS: Eighty-one individuals met inclusion criteria. Overall mortality for the study was 50.2%. The mean elevation in creatinine from admission to initiation of CRRT was 1.6 mg/dL (141.4 micromol/L) in those who lived and 2.6 mg/dL (229.8 micromol/L) in those who died (P = 0.023). Patients admitted with normal renal function who developed ARF while in the hospital had mortality of 56.3%. When available, patients with abnormal renal function at presentation were further classified by either abnormal or normal preadmission creatinine. These patients had mortality of 31.3% and 83.3%, respectively. These differences in mortality were statistically significant. CONCLUSIONS: Increased mortality was significantly associated with the magnitude of change in serum creatinine between admission and initiation of CRRT. Also, patient ARF classification was significantly associated with mortality.     

Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible anti-apoptotic mechanism

The metabolic cocktail of glucose-insulin-potassium (GIK) has been shown to reduce mortality in humans and reduce infarct size in the rat when administered from the onset of reperfusion following an ischemic insult. The mechanisms underlying GIK mediated cardioprotection are, however, still unclear. Recent data implicates insulin "alone" as the major protagonist of cardioprotection when administered at the time of reperfusion. We have therefore begun to investigate an insulin activated signalling pathway and the putative role of apoptosis in this insulin-induced cardioprotection. Simulated ischemia and reoxygenation were induced in rat neonatal cardiocyte experiments. The administration of insulin [0.3 mU/ml] at the moment of reoxygenation (Ins(R)) enhanced myocardial cell viablility as assessed by trypan blue exclusion compared to vehicle alone treated control myocytes (Ins(R)50+/-2%v controls 70+/-1%, P<0.001). This insulin-mediated cardioprotection was due, in part to a reduction in myocyte apoptosis as measured by TUNEL (Ins(R)29+/-2%v controls 49+/-3%, P<0.001) and Annexin V staining (Ins(R)34+/-2%v controls 65+/-3%, P<0.001). These cardioprotective and anti-apoptotic effects of insulin were completely abolished by the tyrosine kinase inhibitor lavendustin A and by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor wortmannin. Thus, we conclude that the early administration of insulin appears to be an effective modality to reduce reoxgygenation injury in cardiocytes, in part, via the attenuation of ischemia/reoxygenation-induced apoptosis. Moreover, the cardioprotective and anti-apoptotic effects of insulin are mediated via tyrosine kinase and PI3-kinase signalling pathways.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

Practice patterns in evaluation of living kidney donors in United network for organ sharing-approved kidney transplant centers

Introduction: The current pattern of evaluation for living kidney donors was investigated. Methods: We designed a 37-question electronic survey to collect information about living kidney donor evaluation. Of the 181 United Network for Organ Sharing (UNOS)-approved centers, 72 responded. Survey responses were coded and downloaded into SPSS. Data was expressed as means and standard deviations or the percentage of centers with specific responses. Results: 66% of the centers used a cut-off of <80 ml/min for exclusion of living kidney donors. 24-hour urine measuring creatinine clearance (CrCl) was the most common screening method for glomerular filtration rate (GFR) assessment in potential living donors. 56% of the centers excluded donors with blood pressure (BP) >140/90, whereas 22.7 and 7.1% excluded patients with pre-hypertension with a cut-off BP of 130/85 and 120/80, respectively. 66% of the centers used 24-hour urine creatinine to assess for proteinuria. 20% of the centers accepted living kidney donors with microalbuminuria and 84% accepted patients with a history of nephrolithiasis. 24% of the centers reported use of formal cognitive testing of potential living donors. Discussion: There were significant variations in exclusion criteria based on GFR, history of kidney stones, body mass index, BP and donors with urinary abnormalities. The definitions for hematuria and proteinuria were variable. There is a need for uniformity in selection and for a living donor registry. We also recommend raising the cut-off for estimated GFR to 90 ml/min to account for 10-15% overestimation when CrCl is used.     

Uteroplacental unit as a source of elevated circulating prorenin levels in normal pregnancy

Circulating levels of inactive renin, that is, prorenin, are increased in normal pregnant women. To determine whether the uteroplacental unit secretes prorenin into the maternal circulation, we measured enzymatically active and inactive renin in plasma simultaneously obtained from the radial artery and uterine vein of 12 normotensive, nonlaboring patients undergoing elective cesarean section at term. We also measured these forms of renin in the umbilical arterial and venous blood of these patients. Our data reveal that the levels of inactive renin in both arterial and uterine venous blood of normal pregnant women are significantly higher than in peripheral venous blood of nonpregnant, normotensive control subjects; normotensive term patients have a ratio of plasma inactive to active renin of 9:1 in contrast to the 1:1 ratio in normotensive nonpregnant subjects; there is a significant uterine arteriovenous difference of prorenin (66.2 +/- 24.4 ng/ml/hr, p less than 0.05) but not of active renin (1.8 +/- 1.5 ng/ml/hr, not significant). These results suggest that the uteroplacental unit contributes to the elevated prorenin levels at term pregnancy.     

Tackling Health Care Disparities: How to Build a Sarcoidosis Center

Sarcoidosis is a multi-organ system inflammatory disease of unknown etiology that disproportionately affects women and black patients in the United States. In addition, woman and minority patients have worse outcomes. In 2015, sarcoidosis physicians in cardiology, pulmonary medicine and rheumatology joined forces to create a multidisciplinary sarcoidosis at Virginia Commonwealth University. In 2019, the clinic was recognized as a World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) Center of Excellence. We identify four pillars of a patient-centered sarcoidosis clinic: clinical care, research, teaching, and community outreach. We detail how each of these facets plays a critical role in improving the health of individual patients, creating a strong infrastructure to improve the future of sarcoidosis treatment, and developing community-based resources that can empower patients. Most importantly, we highlight how a multidisciplinary clinic can help identify and combat healthcare disparities.     

Vascular aneurysms in Ehlers-Danlos syndrome subtypes: A systematic review

Aneurysmal lesions are commonly seen in Ehlers-Danlos Syndrome (EDS). To better identify the regional and vessel-specific spectrum of aneurysms in different subtypes of EDS, we performed a systematic review. We searched Medline for relevant studies from 1963 to April 2022. Studies providing a report of any EDS subtype by genetic diagnosis, histologic analysis, or clinical criteria were included. A total of 448 patients from 220 studies were included. 720 vessel-specific aneurysms were reported: 386 in the abdominopelvic area, 165 in the intracranial region, 98 in the thorax, 2 in the extremities, and 6 in the venous system. In 27 out of the 65 patients with ruptured aneurysms, the ruptured aneurysm was the initial presentation. Multiple aneurysms were present in 163 out of 249 patients who had been systematically evaluated for other locations of aneurysms. The head and neck and abdominopelvic regions are two potential foci for aneurysm formation in patients with EDS. The aneurysm development in EDS is not confined to arteries; the venous system and cardiac septa may also be affected. Many patients develop multiple aneurysms, either at the time of the initial presentation or throughout their lifetime and aneurysm formation or rupture may be the first presentation of EDS.