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Objectives. Urinary albumin excretion is a risk marker for cardiovascular disease (CVD). Studies suggest that urinary orosomucoid may be a more sensitive marker of general endothelial dysfunction than albuminuria. The aim of this population-based cross-sectional study was to examine the associations between urinary orosomucoid to creatinine ratio (UOCR), urinary albumin to creatinine ratio (UACR) and subclinical CVD. Design. From the Tromsø Study (2007/2008), we included all men and women who had measurements of urinary orosomucoid (n = 7181). Among these, 6963 were examined with ultrasound of the right carotid artery and 2245 with echocardiography. We assessed the associations between urinary markers and subclinical CVD measured as intima media thickness of the carotid artery, presence and area of carotid plaque and diastolic dysfunction (DD). UOCR and UACR were dichotomized as upper quartile versus the three lowest. Results. High UOCR, adjusted for UACR, age, cardiovascular risk factors and kidney function, was associated with presence of DD in men (OR: 3.18, 95% CI [1.27, 7.95], p = .013), and presence of plaque (OR: 1.20, 95% CI [1.01, 1.44], p = .038) and intima media thickness in women (OR: 1.34, 95% CI [1.09, 1.65], p = .005). Analyses showed no significant interaction between sex and UOCR for any endpoints. UACR was not significantly associated with DD, but the associations with intima media thickness and plaque were of magnitudes comparable to those observed for UOCR. Conclusions. UOCR was positively associated with subclinical CVD. We need prospective studies to confirm whether UOCR is a clinically useful biomarker and to study possible sex differences.

A multidisciplinary team of doctors is in charge or is involved in the follow-up of patients who undergo solid organ transplantation (SOT). Immunosuppressive drugs are required after SOT, some potential unwanted side effects can be difficult to detect, and physicians must be aware of potential pitfalls. We report a case of a recipient with brittle type 1 diabetes who experienced severe and refractory anemia after pancreas transplantation alone (PTA). Despite a broad diagnostic approach for anemia, the diagnosis was delayed. The patient had normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors in the bone marrow, compatible with pure red cell aplasia (PRCA). Analyses of serological parvovirus B19 anti-IgM and anti-IgG antibodies, including PCR, were initially inconclusive/negative. The diagnosis of parvovirus B19 infection was confirmed after bone marrow biopsy with immunohistochemical staining for parvovirus B19. A retrospective analysis revealed an early post-transplant primary parvovirus B19 infection. The patient was successfully treated with intravenous immunoglobulin (IVIg) therapy. There is a risk of diagnostic delay for the less common types of anemia following SOT. Parvovirus B19 infection-associated PRCA is curable in SOT recipients and should be actively considered in patients with persistent anemia and low reticulocytes.

Supplemental Digital Content is available in the text., Background. Endothelial dysfunction is an early and potentially reversible stage in the atherosclerotic process. We assessed endothelial dysfunction noninvasively in kidney transplant recipients (KTRs) and evaluated the association with mortality and graft outcomes. Methods. Flow-mediated dilation (FMD) was measured in arteria brachialis by ultrasound, with baseline diameters obtained at rest and maximal diameters obtained during reactive hyperemia occurring after 5 min of forearm occlusion. FMD% is the percentage difference of flow-mediated dilation relative to baseline. Endpoints on mortality and graft outcomes were collected from The Norwegian Renal Registry. The distribution of risk according to FMD levels was assessed in Cox regression using a restricted cubic spline function. FMD was dichotomized using receiver operating characteristic analysis to identify optimal cut points at maximal sensitivity and specificity. Results. From a total of 269 KTRs in 2012, 152 (56.5%) were eligible and examined 10 wk after transplantation, and 145 had successful FMD measurements. During a mean follow-up of 6.5 y, 26 patients died, 11 lost their graft, and 34 experienced either graft loss or death. Mortality increased with lower FMD levels until about 5% dilation and did not change with further reduction in FMD% (P for nonlinearity

Estimert glomerulær filtrasjonshastighet er etablert som klinisk rutinemål for nyrefunksjon, men estimatet har begrensninger og kan ikke brukes i alle kliniske situasjoner. Estimert glomerulær filtrasjonshastighet har en høy variasjonskoeffisient, og ved avvik i pasientens høyde, vekt eller muskelmasse kan estimatet bli unøyaktig. Hvis det er avgjørende å ha et nøyaktig mål på nyrefunksjonen, kan man måle glomerulær filtrasjonshastighet ved hjelp av en eksogen substans.

Several epidemiological studies have pointed at serum uric acid (SUA) as an independent risk factor for mortality, diabetes, hypertension, cardiovascular and kidney disease; however, no clear pathogenic pathway is established. Uric acid (UA) crystals show pro-inflammatory properties and can thus create or contribute to the state of chronic low-grade inflammation, a widely accepted pathogenic mechanism in several of the above-mentioned pathologies. On the other hand, soluble uric acid possesses antioxidant properties that might attenuate inflammatory responses. We aimed to explore the net effects of experimentally rising SUA in human whole blood cultures on several mediators of inflammation. production of tNF-α, IL-1ß, IL-1RA, MCP-1 and IL-8 was assessed upon addition of 200 μM UA, 500 μM UA or monosodium urate (MSU) crystals in the presence or absence of 5 ng/ml lipopolysaccharide (LPS). RT-qPCR and multiplex bead based immunoassay were used to measure mRNA expression and cytokine release at 2 and 4 h of culture, respectively. 14C labeled UA was used to assess intracellular uptake of UA. We show that crystallized, but not soluble, UA induces production of pro-inflammatory mediators in human whole blood. Soluble UA is internalized in blood cells but does not potentiate or reduce LPS-induced release of cytokines. Crystallized but not soluble uric acid elicits pro-inflammatory response in short-term whole blood cultures from healthy men The authors thank Gro Bolstad for technical assistance, Trine Kalstad for help with Bio-Plex multiplex analysis, Thomas Vennø Andreassen for advice and technical assistance, Knut Steinnes for technical assistance. The publication charges for this article have been funded by a grant from the publication fund of UiT - The Arctic University of Norway. The study has been funded by the UiT – The Arctic University of Norway and the Tromsø Research Foundation (grant nr 311333/A22349).

Source at https://dx.doi.org/10.1002/ehf2.12134 Aims: To investigate whether serum uric acid predicts adverse outcomes in persons with indices of diastolic dysfunction in a general population. Methods and results: We performed a prospective cohort study among 1460 women and 1480 men from 1994 to 2013. End- points were all-cause mortality, incident myocardial infarction, and incident ischaemic stroke. We strati fi ed the analyses by echocardiographic markers of diastolic dysfunction, and uric acid was the independent variable of interest. Hazard ratios (HR) were estimated per 59 μ mol/L increase in baseline uric acid. Multivariable adjusted Cox proportional hazards models showed that uric acid predicted all-cause mortality in subjects with E/A ratio < 0.75 (HR 1.12, 95% con fi dence interval [CI] 1.00 – 1.25) or E/A ratio > 1.5 (HR 1.51, 95% CI 1.09 – 2.09, P for interaction between E/A ratio category and uric acid = 0.02). Elevated uric acid increased mortality risk in persons with E-wave deceleration time < 140 ms or > 220 ms (HR 1.46, 95% CI 1.01 – 2.12 and HR 1.13, 95% CI 1.02 – 1.26, respectively; P for interaction = 0.04). Furthermore, in participants with isovolumetric relaxation time ≤ 60 ms, mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02 – 12.26, P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03 – 2.53, P for interaction = 0.047). Conclusions: Increased uric acid was associated with higher all-cause mortality risk in subjects with echocardiographic indices of diastolic dysfunction, and with higher ischaemic stroke risk in persons with severely enlarged left atria.

Published version, also available at http://dx.doi.org/10.1186/s12882-015-0207-1 Background: The role of uric acid in development of renal dysfunction (RD) remains controversial. Earlier studies have reported inconsistent results, possibly because of their varying ability to adjust for confounding. The impact of longitudinal change in uric acid on renal outcome has not been assessed previously. We aimed to study the impact of change in serum uric acid (SUA) as well as baseline SUA on the development of RD. Methods: In a prospective cohort study, we assessed the associations between change in SUA during follow-up, baseline SUA and RD (defined as albumin-creatinine-ratio (ACR) ≥1.13 mg albumin/mmol creatinine and/or eGFR < 60 ml/min/1.73 m2) in a large cohort from a general population participating in the Tromsø Study (n = 2637). Participants were stratified according to tertiles of change in SUA between baseline (1994/95) and follow-up 13 years later. (upper tertile: SUA increasing group, two lower tertiles: SUA non-increasing group). Logistic regression analysis was applied with RD and each component of RD after 7 and 13 years as the dependent variables. Adjustments were made for baseline eGFR, cardiovascular risk factors, and the use of antihypertensive drugs including diuretics. Results: After excluding participants with RD at baseline, SUA increasers, compared to SUA non-increasers, had a doubled risk of RD after 7 years (odds ratio 2.00, (95 % CI 1.45, 2.75)). Odds ratio for RD in SUA increasers after 13 years was 2.18 (95 % CI 1.71, 2.79). The risk of developing ACR ≥1.13 mg/mmol alone was not significantly increased after 7 years (odds ratio 1.30 (95 % CI 0.90, 1.89), but after 13 years (odds ratio 1.43 (95 % CI 1.09, 1.86)). An increase in baseline SUA of 59 μmol/L (1 mg/dL) gave an odds ratio for RD after 13 years of 1.16 (95 % CI 1.04, 1.29). Conclusion: An increase in SUA during follow-up was associated with an increased risk of developing RD after 7 and 13 years.

Advanced glycation end products (AGEs) react non-enzymatically with tissue proteins to form irreversible structures involved in atherosclerosis, nephropathy, retinopathy, neuropathy, and wound healing. Studies on AGE-inhibitors have demonstrated possible prevention of diabetes complications. The present open label study was conducted on aminoguanidine (AGu), an inhibitor of AGE-formation, to examine potential effects on wound healing in diabetes type 2-like db/db mice during 5 - 6 weeks. The animals were divided into 4 groups: AGu from the day of wounding (day 0) topically and/or systemically in drinking water (1 g/L; group 1, n = 13); AGu 1 g/L in drinking water from 7 weeks prior to day 0 (group 2, n = 21); AGu 5 g/L in drinking water from 9 - 11 weeks prior to day 0 (group 3, n = 6); placebo controls (group 4, n = 8). Results: Glycated hemoglobin (A1C) was significantly lower in group 3 compared to the other groups (P < 0.05). Percentage change in A1C and body weight from baseline to the end of the experiment were both related to the AGu doses (1 or 5 g/L; A1C-change, P = 0.01; weight-change, P = 0.04, both for linear trend across groups 4, 2, and 3, respectively). Even so, percentage wound closure was not improved in the AGu-treated groups compared to controls (P ≥ 0.8).