Summary. Background: The optimal approach for venous thrombosis (VTE) prophylaxis during pregnancy and postpartum in women with an increased risk of VTE is not established. Objectives: To evaluate... Show moreSummary. Background: The optimal approach for venous thrombosis (VTE) prophylaxis during pregnancy and postpartum in women with an increased risk of VTE is not established. Objectives: To evaluate the effectiveness, represented as the incidence of pregnancy-related VTE, and safety, represented as incidence of postpartum hemorrhage (PPH), of a protocol recommending prophylaxis with low-dose low-molecular-weight heparin (LMWH) in women at intermediate to high risk of VTE. Patients/methods: In this retrospective cohort study, we analyzed 34 women (44 pregnancies) with intermediate risk of VTE who received low-dose LMWH for 6 weeks postpartum and 57 women (82 pregnancies) with high risk of VTE who received low-dose LMWH during pregnancy and for 6 weeks postpartum. Pregnancy-related VTE was defined as VTE during pregnancy or ≤ 3 months postpartum. PPH was defined as blood loss > 500 mL and severe PPH as blood loss > 1000 mL. Results: The incidence of pregnancy-related VTE was 5.5% (95% CI, 2.4-12.3) despite prophylaxis with low-dose LMWH. All events occurred in women at high risk, with a postpartum incidence of 7.0% (95% CI, 2.9-16.7) and antepartum incidence of 1.8% (95% CI, 0.4-9.2). The risk of PPH was 21.6% (95% CI, 14.3-31.3) and severe PPH 9.1% (95% CI, 4.7-16.9), which was not different in women who started LMWH postpartum and those who used LMWH during pregnancy. Conclusions: Although prophylaxis with low-dose LMWH during pregnancy and postpartum proved to be safe, the risk of pregnancy-related VTE is considerable in women with a high risk of VTE. VTE prophylaxis with low-dose LMWH may not be sufficiently effective in these women. Show less
Background: Disease monitoring of autosomal dominant polycystic kidney disease (ADPKD) will become more important with potential upcoming therapeutic interventions. Because serum creatinine level... Show moreBackground: Disease monitoring of autosomal dominant polycystic kidney disease (ADPKD) will become more important with potential upcoming therapeutic interventions. Because serum creatinine level is considered of limited use and measurement of effective renal blood flow (ERBF) and total renal volume are time consuming and expensive, there is a need for other biomarkers. We aimed to investigate which urinary markers have increased levels in patients with ADPKD; whether these urinary markers are associated with measured glomerular filtration rate (mGFR), ERBF, and total renal volume; and whether these associations are independent of albuminuria (urine albumin excretion [UAE]). Study Design: Diagnostic test study. Setting & Participants: 102 patients with ADPKD (Ravine criteria) and 102 age-and sex-matched healthy controls. Index Test: 24-hour urinary excretion of glomerular (immunoglobulin G), proximal tubular (kidney injury molecule 1 [KIM-1], N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin [NGAL], and beta(2)-microglobulin), and distal tubular (heart-type fatty acid binding protein [H-FABP]) damage markers and inflammatory markers (monocyte chemotactic protein 1 [MCP-1] and macrophage migration inhibitory factor). Reference Test: Disease severity assessed using measures of kidney function (mGFR and ERBF, measured using clearance of iothalamate labeled with iodine 125 and hippuran labeled with iodine 131 during continuous infusion, respectively) and structure (total renal volume, measured using magnetic resonance imaging). Other Measurements: 24-hour UAE. Results: In 102 patients with ADPKD (aged 40 +/- 11 years; 58% men), levels of all measured urinary biomarkers were increased compared with healthy controls. Excretion of immunoglobulin G and albumin relatively were most increased. ERBF and mGFR values were associated with urinary excretion of beta(2)-microglobulin, NGAL, and H-FABP independent of UAE, whereas total renal volume was associated with KIM-1, NGAL, and MCP-1 independent of UAE. Limitations: Cross-sectional, single center. Conclusions: Levels of markers for multiple parts of the nephron are increased in patients with ADPKD. In addition to measurement of UAE, measurement of urinary beta(2)-microglobulin, KIM-1, H-FABP, MCP-1, and especially NGAL could be of value for determination of disease severity in patients with ADPKD. Am J Kidney Dis 56: 883-895. (C) 2010 by the National Kidney Foundation, Inc. Show less
Urinary albumin excretion is a powerful predictor of progressive cardiovascular and renal disease. In rats and humans, administration of a synthetic vasopressin analogue, 1-desamino-8-D-arginine... Show moreUrinary albumin excretion is a powerful predictor of progressive cardiovascular and renal disease. In rats and humans, administration of a synthetic vasopressin analogue, 1-desamino-8-D-arginine-vasopressin, increases urinary albumin excretion; however, it is unknown if endogenous vasopressin levels influence albumin excretion. To determine this we measured copeptin, a marker of endogenous vasopressin levels, and its association with urinary albumin excretion in 7593 patients in the PREVEND study, a prospective population based, observational cohort. Urinary albumin excretion was measured in two consecutive 24-h urine samples by nephelometry while copeptin was measured by an immunoassay. Median copeptin concentrations were significantly higher in males than females and high levels were associated with significantly lower 24-h urine volumes of high osmolarity. With increasing quintiles of copeptin levels, the percentage of microalbuminuric subjects increased from 13 to 25 for males and from 8 to 15 for females. This association was independent of age and other potential confounders; however, we found an interaction between age and copeptin in their association with urinary albumin excretion. Our study shows that plasma copeptin levels are associated with microalbuminuria, consistent with the hypothesis that vasopressin is involved in urinary albumin excretion. If future studies show that this association is causal, then drinking more water or pharmacological intervention to decrease plasma vasopressin may have beneficial effects on the kidney, especially in the elderly. Kidney International (2010) 77, 29-36; doi:10.1038/ki.2009.397; published online 21 October 2009 Show less