IgA vasculitis nephritis-outcomes in adult-onset disease.

OBJECTIVES: IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18-34), middle aged adults (35-64) and elderly patients (≥64 years) focusing on kidney outcomes. METHODS: We identified patients with renal biopsy confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression. RESULTS: We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% were elderly (>64 years). Median follow up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle aged (13.7%) and younger adults (2.9%)(χ2 11.6, p= 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and eGFR < 30mls/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression. CONCLUSIONS: Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV.

Efficacy of beetroot juice on reducing blood pressure in hypertensive adults with autosomal dominant polycystic kidney disease (BEET-PKD): study protocol for a double-blind, randomised, placebo-controlled trial.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) impaired nitric oxide (NO) synthesis, in part, contributes to early-onset hypertension. Beetroot juice (BRJ) reduces blood pressure (BP) by increasing NO-mediated vasodilation. The aim of this double-blind, randomised, placebo-controlled study is to test the hypothesis that BRJ reduces systolic and diastolic clinic BP in hypertensive adults with ADPKD. METHODS: Participants with ADPKD and treated hypertension (n = 60) will be randomly allocated (1:1) to receive a daily dose of either nitrate-replete (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. The co-primary outcomes are change in mean systolic and diastolic clinic BP before and after 4 weeks of treatment with daily BRJ. Secondary outcomes are changes in daily home BP, urinary albumin to creatinine ratio, serum and salivary nitrate/nitrite levels and serum asymmetric dimethylarginine levels before and after 4 weeks of BRJ. DISCUSSION: The effect of BRJ in ADPKD has not been previously tested. BRJ is an accessible, natural dietary supplement that, if effective, will provide a novel adjunctive approach for treating hypertension in ADPKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05401409. Retrospectively registered on 27th May 2022.

Pharmacological Evaluation of Artemisia cina Crude CO2 Subcritical Extract after the Removal of Santonin by Means of High Speed Countercurrent Chromatography.

Artemisia species are highly important due to their economic significance as medicines, fodder and food. Artemisia cina is an endemic species to Kazakhstan. In folk medicine, water extract of A. cina was used in the treatment of bronchial asthma while the alcohol extract has larvicidal and antituberculosis activity. The most common and most extensively studied compound from this species is the terpenoid santonin. The toxicity of this compound occurs at the doses of 60 mg for children and 200 mg for adults causing among other issues xanthopsia, leading to blindness. Having this in mind, the main idea of this work was to remove santonin from the crude extract and to check if the santonin-free extract would still be of any pharmacological importance. A CO2 subcritical extract was chromatographed using high-speed countercurrent chromatography (HSCCC) for the removal of santonin. The santonin-free CO2 subcritical extract (SFCO2E) as well as the isolated compound pectolinarigenin, a flavonoid, were assessed for their pharmacological actions. From the results obtained we can safely suggest that HSCCC is an efficient methodology to completely remove santonin from the CO2 subcritical extract. It was also possible to observe promising antinociceptive and anti-inflammatory activities for both SFCO2E and pectolinarigenin at concentrations that can justify the production of a phytomedicine with this endemic plant from Kazakhstan.

High Incidence of Arterial and Venous Thrombosis in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

OBJECTIVE: To determine the incidence of arterial thrombotic events (ATE) and venous thromboembolism (VTE) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This is a retrospective cohort study presenting the incidence of ATE (coronary events or ischemic stroke) and VTE [pulmonary embolism (PE) or deep venous thrombosis (DVT)] in patients diagnosed with AAV between 2005 and 2014. RESULTS: There were 204 patients with AAV who were identified. Median followup for surviving patients was 5.8 (range 1-10) years, accounting for 1088 person-years (PY). The incidence of ATE was 2.67/100 PY (1.56 for coronary events and 1.10 for ischemic stroke) and for VTE was 1.47/100 PY (0.83 for DVT only and 0.64 for PE with/without DVT). On multivariate analysis, prior ischemic heart disease (IHD) and advancing age were the only independent predictors of ATE. Among patients without prior IHD or stroke, the incidence of ATE remained elevated at 2.32/100 PY (1.26 for coronary events and 1.06 for ischemic stroke). ATE, but not VTE, was an independent predictor of all-cause mortality. Event rates for both ATE and VTE were highest in the first year after diagnosis of AAV but remained above the population incidence during the 10-year followup period. In comparison to reported rates for the UK population, the event rates in our AAV patients were 15-times higher for coronary events, 11-times higher for incident stroke, and 20-times higher for VTE. CONCLUSION: Patients with AAV have a high incidence of arterial and venous thrombosis, particularly in the first year after diagnosis.

Quantification of santonin in eight species of Artemisia from Kazakhstan by means of HPLC-UV: Method development and validation.

Santonin, a powerful anthelmintic drug that was formely used to treat worms, is Artemisia cina's main constituent. However, due to its toxicity to humans, it is no longer in use. Kazakhstan is looking to introduce this plant as an anthelmintic drug for veterinary purposes, despite the known toxic properties of the santonin. The objective of this study was to develop a fast and specific method for the identification of santonin and its precise quantitation using HPLC-UV in order to avoid unnecessary intoxication, which is paramount for the development of veterinary medicines. The results obtained showed that santonin appears at around 5.7 minutes in this very reliable HPLC method. The validation of the method was performed by the investigation of parameters such as precision, accuracy, reproducibility and recovery. The method was used to identify and quantify santonin in leaves of A. scoparia, A. foetida, A. gmelinni, A. schrenkiana, A. frigida, A. sublesingiana, A terra-albae, and A. absinthium from Kazakhstan as well as in three different extracts of leaves of A. cina. This study has provided a faster and simpler method for the identification and quantification of this compound in other species of Artemisia of economic importance.

Bortezomib in ABO-incompatible kidney transplant desensitization: a case report.

Positive B cell crossmatch accompanied by high levels of pre-transplant human leukocyte antigen donor-specific antibodies are associated with adverse graft outcomes in kidney transplant recipients. Targeting plasma cells, the main antibody producing cells, with the proteasome inhibitor bortezomib may be a promising desensitization strategy. We report using a combination of bortezomib and plasmapheresis to desensitize a highly sensitized kidney transplant recipient for an ABO-incompatible living donor kidney transplant. The flow cytometric B cell crossmatch was positive on presentation. After treatment, the anti-A titres fell from 1:64 to 1:4, and a negative B flow cytometric crossmatch was achieved prior to transplantation. The combined approach of bortezomib to abrogate antibody production at the plasma cell level, followed by plasmapheresis and low-dose intravenous immunoglobulin to remove in-circulation alloantibodies, has proven to be effective in our case. Bortezomib may play a role in highly sensitized renal transplants.

Choisyaternatine, a new alkaloid isolated from Choisya ternata.

One novel compound was isolated from the hexane extract of Choisya ternata Kunth. leaves, choisyaternatine (1), together with the known compounds tecleamaniensine A (2), lup-20(29)-en-3ß-ol (lupeol) (3), lup-20(29)-en-3ß,24-diol (4), ß-sitosterol glucoside (5), and skimmianine (6), plus the following known compounds from the dichloromethane extract, choisyine (7) and 6-methoxy-7,8-methylenedioxycoumarin (8). Compounds 2-5 are reported for the first time in this species. The structures of isolated compounds were elucidated by extensive spectroscopic analyses and comparison with previously reported spectroscopic data. The structure of choisyaternatine was further confirmed based on X-ray data analysis.

Gender discrimination in the influence of hyperglycemia and hyperosmolarity on rat aortic tissue responses to insulin.

Hyperglycaemia initiates endothelial dysfunction causing diabetic macro- and micro-vasculopathy, the main causes of morbidity and mortality in diabetes mellitus. The vasculopathy exhibits gender peculiarities. We therefore explored gender differences in comparing the effects of hyperglycaemia (50 mM) per se with its hyperosmolar (50 mM) effects on vascular tissue responses to insulin. Endothelium-intact or denuded thoracic aortic rings from age-matched male and female Sprague-Dawley rats were incubated for 10 min or 6 h (acute versus chronic exposure) in normal, hyperglycaemic or hyperosmolar Krebs solution. Relaxant responses to insulin (6.9x10(-7)-6.9x10(-5) M) of the phenylephrine-contracted tissues were recorded. Endothelium denudation in both genders inhibited relaxation to insulin in all conditions, more significantly in female than in male tissues, suggesting the female response to insulin is more endothelium-dependent than the male. Acutely and chronically exposed normoglycemic endothelium-intact or -denuded tissues responded similarly to insulin. Chronic hyperglycemic or hyperosmolar exposure did not alter the endothelium-denuded tissue responses to insulin, whereas the responses of the endothelium-intact male and female hyperosmolar, and male hyperglycemic tissues were enhanced. The results show that insulin exerts an endothelium-dependent and independent relaxation with the female tissue responses more endothelium-dependent than the male. The data also suggest that hyperosmolarity per se enhances aortic tissue relaxant responses to insulin whereas hyperglycemia per se inhibits the same and more so in female than male tissues. These effects are endothelium-dependent.