A proteinuria cut-off level of 0.7 g /day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: Data from the MAINTAIN Nephritis Trial

Background: Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). Methods: Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). Results: After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells 645/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. Conclusions: In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts

Urea levels and cardiovascular disease in patients with chronic kidney disease

Background: Elevated serum urea levels are common in moderate-to-advanced chronic kidney disease (CKD). Several studies have shown that urea is a direct and indirect uraemic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD. Methods: CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 <10.5, T2 10.5-15.1 and T3 ≥15.1 mmol/L). Cox proportional hazard models were used to estimate hazard ratios (HRs) for first atheromatous or non-atheromatous cardiovascular (CV) events and all-cause mortality before RRT. The models were adjusted for baseline comorbidities, laboratory data and medications. Findings: Of the 2507 included patients median [interquartile range (IQR)] age: 69 [61-77]; mean (standard deviation) estimated glomerular filtration rate (eGFR) 33.5 (11.6) mL/min/1.73 m², 54% had a history of cardiovascular disease. After multiple adjustments for CV risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and non-atheromatous CV events than patient in T1 (n events = 451, HR [95% CI]: 1.93 [1.39; 2.69]). The adjusted HRs for death before RRT (n events = 407) were 1.31 [0.97; 1.76] and 1.73 [1.22; 2.45] for patients T2 and those in T3, respectively. Interpretation: Our data suggested that urea is a predictor of CV outcomes beyond CV risk factors including eGFR. © 2022 The Author(s). Published by Oxford University Press on behalf of the ERA

Evolution of blood coagulation activators and inhibitors in the healthy human fetus

Blood coagulation proteins were determined in 285 healthy fetuses from 19 to 38 weeks' gestation and compared with those of 60 normal full- term newborns and 40 adult controls. Prolongation of the coagulation screening tests, prothrombin time, activated partial prothrombin time, and thrombin clotting time, in fetuses throughout intrauterine life was explained by low levels of vitamin K-dependent factors (II, VII, IX, and X), contact factors (XI, XII, prekallikrein, and high-molecular- weight kininogen), factor V, factor VIII, and fibrinogen. Low levels of antithrombin III, heparin cofactor II, protein C and protein S, and tissue factor pathway inhibitor were also found, and these probably contributed to a satisfactory hemostatic balance. Some of these parameters were evaluated by both immunologic and functional assays to detect possible “fetal” proteins. An increase in factor levels was observed after the thirty-fourth week of intrauterine life for most of the coagulation activators and inhibitors, but only factors V and VIII reached adult values at birth. This study therefore showed that fetal hemostasis is a dynamic system that evolves gradually toward the neonatal state and then toward the adult state.</jats:p

Evolution of blood coagulation activators and inhibitors in the healthy human fetus

Abstract Blood coagulation proteins were determined in 285 healthy fetuses from 19 to 38 weeks' gestation and compared with those of 60 normal full- term newborns and 40 adult controls. Prolongation of the coagulation screening tests, prothrombin time, activated partial prothrombin time, and thrombin clotting time, in fetuses throughout intrauterine life was explained by low levels of vitamin K-dependent factors (II, VII, IX, and X), contact factors (XI, XII, prekallikrein, and high-molecular- weight kininogen), factor V, factor VIII, and fibrinogen. Low levels of antithrombin III, heparin cofactor II, protein C and protein S, and tissue factor pathway inhibitor were also found, and these probably contributed to a satisfactory hemostatic balance. Some of these parameters were evaluated by both immunologic and functional assays to detect possible “fetal” proteins. An increase in factor levels was observed after the thirty-fourth week of intrauterine life for most of the coagulation activators and inhibitors, but only factors V and VIII reached adult values at birth. This study therefore showed that fetal hemostasis is a dynamic system that evolves gradually toward the neonatal state and then toward the adult state.</jats:p