IntroductionA systemic anticoagulation is often required to prevent circuit and filter clotting in ICU patients undergoing continuous renal replacement therapy (CRRT). A regional citrate-based anticoagulation (RCA) does not induce a systemic anticoagulation and prolongs the filter lifespan, but metabolic side-effects have been associated with this therapy. We conducted a randomized controlled trial with patients requiring CRRT to determine whether RCA using a balanced predilution replacement fluid is more effective than heparin in terms of renal replacement delivered dose and safety profile.MethodsOne hundred and three patients with AKI requiring CRRT were included. The patients were randomized to either CRRT with RCA or heparin anticoagulation. Primary endpoints were effective daily delivered RRT dose during the first 3 days of CRRT and filter lifespan. Secondary endpoints were 28-day and 90-day survival and severe metabolic complications and bleeding disorders.ResultsMedian CRRT duration was 3.0 (2–6) days. Effective delivered daily RRT doses were 29 ± 3 and 27 ± 5 mL/kg/hr in the RCA and heparin groups, respectively (p = 0.005). Filter lifespans were 49 ± 29 versus 28 ± 23 hrs in the RCA and heparin groups (p = 0.004). Survival rates at 28 and 90 days were 80-74% in the RCA and 74-73% in the heparin group. Electrolytes and acid–base disturbances were uncommon and transient in patients treated with RCA.ConclusionsThese results show that RCA is superior to heparin-based anticoagulation in terms of delivered RRT dose and filter life span and is a safe and feasible method. This does not translate into an improvement in short term survival.Trial registrationClinicalTrials.gov NCT01269112. Registered 3rd January 2011.

In rodents, parietal epithelial cells (PECs) migrating onto the glomerular tuft participate in the formation of focal segmental glomerulosclerosis (FSGS) lesions. We investigated whether immunohistologic detection of PEC markers in the initial biopsies of human patients with first manifestation of idiopathic nephrotic syndrome with no immune complexes can improve the sensitivity to detect sclerotic lesions compared with standard methods. Ninety-five renal biopsies were stained for claudin-1 (PEC marker), CD44 (activated PECs), and LKIV69 (PEC matrix); 38 had been diagnosed as early primary FSGS and 57 as minimal change disease. PEC markers were detected on the tuft in 87% of the biopsies of patients diagnosed as primary FSGS. PEC markers were detected in FSGS lesions from the earliest stages of disease. In minimal change disease, no PEC activation was observed by immunohistology. However, in 25% of biopsies originally diagnosed as minimal change disease the presence of small lesions indicative of a sclerosing process were detected, which were undetectable on standard periodic acid-Schiff staining, even though only a single histologic section for each PEC marker was evaluated. Staining for LKIV69 detected lesions with the highest sensitivity. Two novel PEC markers A-kinase anchor protein 12 and annexin A3 exhibited similar sensitivity. In summary, detection of PECs on the glomerular tuft by immunostaining improves the differentiation between minimal change disease and primary FSGS and may serve to guide clinical decision making.

PCT may be useful to identify severely ill elderly patients admitted to an acute geriatric ward but not to discriminate patients with infection from those without.