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Acute intermittent porphyria (AIP) is an inherited metabolic disorder associated with complications including kidney failure and hepatocellular carcinoma, probably caused by elevations in the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA). This study explored differences in modern biomarkers for renal and hepatic damage between AIP patients and controls. Urine PBG testing, kidney injury panels, and liver injury panels, including both routine and modern biomarkers, were performed on plasma and urine samples from AIP cases and matched controls (50 and 48 matched pairs, respectively). Regarding the participants' plasma, the AIP cases had elevated kidney injury marker-1 (KIM-1, p = 0.0002), fatty acid-binding protein-1 (FABP-1, p = 0.04), and α-glutathione S-transferase (α-GST, p = 0.001) compared to the matched controls. The AIP cases with high PBG had increased FABP-1 levels in their plasma and urine compared to those with low PBG. In the AIP cases, KIM-1 correlated positively with PBG, CXCL10, CCL2, and TCC, and the liver marker α-GST correlated positively with IL-13, CCL2, and CCL4 (all p < 0.05). In conclusion, KIM-1, FABP-1, and α-GST could represent potential early indicators of renal and hepatic damage in AIP, demonstrating associations with porphyrin precursors and inflammatory markers.

In the inherited metabolic disorder acute intermittent porphyria (AIP), high sugar intake prevents porphyric attacks due to the glucose effect and the following high insulin levels that may lower AIP disease activity. Insulin resistance is a known risk factor for periodontitis and sugar changes diabetogenic hormones and affects dental health. We hypothesized differences in homeostasis model assessment (HOMA) scores for insulin resistance in AIP cases vs. controls and in those with periodontitis. Our aim was to systematically study dental health in AIP as poor dental health was previously only described in case reports. Further, we aimed to examine if poor dental health and kidney failure might worsen AIP as chronic inflammation and kidney failure might increase disease activity. In 47 AIP cases and 47 matched controls, X-rays and physical examination of clinical attachment loss (CAL), probing pocket depth (PPD), and decayed missing filled teeth (DMFT) were performed. Dietary intake was evaluated through a diet logbook. Plasma cytokines and diabetogenic hormones were measured using multiplex technology and urine porphobilinogen and kidney and liver function by routine methods. An excel spreadsheet from the University of Oxford was used to estimate HOMA scores; beta cell function, HOMA%B (%B), insulin sensitivity, HOMA%S (%S), and insulin resistance HOMA-IR (IR), based on glucose and plasma (P) C-peptide. The Wilcoxon matched-pairs signed rank test, the Mann−Whitney U-test, and Spearman’s non-parametric correlation were used. Insulin (p = 0.007) and C-peptide (p = 0.006) were higher in the AIP cases with periodontitis versus those without. In AIP patients, the liver fibrosis index 4 correlated with DMFT (p < 0.001) and CAL ≥4 mm (p = 0.006); the estimated glomerular filtration rate correlated with DMFT (p < 0.001) and CAL ≥4 mm (p = 0.02). CAL ≥4 mm was correlated with chemokine ligand 11 and interleukin (IL)-13 (p = 0.04 for both), and PPD >5 mm was correlated with plasminogen activator inhibitor-1 (p = 0.003) and complement component 3 (p = 0.02). In conclusion, dental health in AIP cases was correlated with insulin resistance, inflammatory markers, and biomarkers of kidney and liver function, demonstrating that organ damage in the kidney and liver are associated with poorer dental health.

Background: Lifestyle factors, including a low intake of carbohydrates, dieting, alcohol consumption, cigarette smoking and stress are some of the possible triggers of attacks in acute intermittent porphyria (AIP). The influence of lifestyle factors, including energy intake, diet and alcohol consumption on the biochemical disease activity in AIP and biochemical nutritional markers were examined., Methods: A case-control study with 50 AIP cases and 50 controls matched for age, sex and place of residence was performed. Dietary intake was registered using a food diary in 46 matched pairs. Symptoms, alcohol intake, stress and other triggering factors of the last AIP attack were recorded on questionnaires. Porphyrin precursors, liver and kidney function markers, vitamins, diabetogenic hormones and other nutritional biomarkers were analyzed by routine methods. The Wilcoxon matched-pairs signed rank test was used to compare the cases vs. controls. The Spearman's rank correlation coefficient was used on the cases., Results: Increasing total energy intake was negatively correlated with the biochemical disease activity. The intake of carbohydrates was lower than recommended, i.e., 40 and 39% of total energy intake in the AIP cases and controls, respectively. The plasma resistin level was significantly higher (p = .03) in the symptomatic than asymptomatic cases. Plasma insulin was lower in those with high porphobilinogen levels. The intake of sugar and candies were higher in the AIP cases with low U-delta aminolevulinic acid (ALA) levels (p = .04). Attacks were triggered by psychological stress (62%), physical strain (38%), food items (24%) and alcohol (32%) in the 34 symptomatic cases. Alcohol was used regularly by 88% of the cases (3.2 g ethanol/day) and 90% of the controls (6.3 g/day), but the intake was significantly lower in symptomatic than in asymptomatic cases (p = .045)., Conclusion: A high intake of energy, sugar and candies and a higher insulin level were associated with a lower biochemical disease activity. The resistin level was higher in the symptomatic than the asymptomatic cases. AIP patients drink alcohol regularly, but the intake was significantly lower in the symptomatic cases., Trial Registration: ClinicalTrials.gov Identifier: NCT01617642., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Cytokines are potentially useful biomarkers of sepsis and other inflammatory conditions. Many cytokines can be released by leukocytes and platelets after sampling. The sampling and processing techniques are consequently critically important to measure the in vivo levels. We therefore examined the effects of four different anticoagulants, EDTA, citrate, lepirudin, heparin compared to serum, on the levels of 27 different cytokines. The effects of storage temperature, freezing and thawing on the plasma cytokines were examined. Cytokines were analysed using a multiplex immunoassay. The cytokine levels in serum were significantly higher compared with plasma, consistent with release of cytokines in vitro during coagulation. In general, the lowest values for all cytokines were found in EDTA samples, stored on crushed ice, centrifuged within 4h and thereafter stored at -80°C. MCP-1 and MIP-1β levels were highest in heparin plasma and storage of blood for up to 4h at room temperature significantly increased the interleukin (IL)-2, IL-6, IL-8, IFN-γ and GM-CSF levels in EDTA plasma, indicating post-sampling release. In contrast, the IP-10 levels were unaffected by sample storage at both temperatures. Our results indicate that the cytokines were more stable in plasma than in whole blood after sampling. Thus, cytokines should be analysed in EDTA plasma samples stored on ice and centrifuged within 4h. Based on these data, the reference ranges of 27 cytokines in EDTA plasma in 162 healthy human donors were calculated., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Regular measurement of prothrombin time as an international normalized ratio PT (INR) is mandatory for optimal and safe use of warfarin. Scandinavian evaluation of laboratory equipment for primary health care (SKUP) evaluated the microINR portable coagulometer (microINR ® ) (iLine Microsystems S.L., Spain) for measurement of PT (INR). Analytical quality and user-friendliness were evaluated under optimal conditions at an accredited hospital laboratory and at two primary health care centres (PHCCs). Patients were recruited at the outpatient clinic of the Laboratory of Medical Biochemistry, St Olav's University Hospital, Trondheim, Norway (n = 98) and from two PHCCs (n = 88). Venous blood samples were analyzed under optimal conditions on the STA-R ® Evolution with STA-SPA + reagent (Stago, France) (Owren method), and the results were compared to capillary measurements on the microINR ® . The imprecision of the microINR ® was 6% (90% CI: 5.3-7.0%) and 6.3% (90% CI: 5.1-8.3) in the outpatient clinic and PHCC2, respectively for INR ≥2.5. The microINR ® did not meet the SKUP quality requirement for imprecision ≤5.0%. For INR <2.5 at PHCC2 and at both levels in PHCC1, CV% was ≤5.0. The accuracy fulfilled the SKUP quality goal in both outpatient clinic and PHCCs. User-friendliness of the operation manual was rated as intermediate, defined by SKUP as neutral ratings assessed as neither good nor bad. Operation facilities was rated unsatisfactory, and time factors satisfactory. In conclusion, quality requirements for imprecision were not met. The SKUP criteria for accuracy was fulfilled both at the hospital and at the PHCCs. The user-friendliness was rated intermediate.