Search

Ischaemia-reperfusion (IR) injury is a composite of the injury sustained during a period of reduced or absent blood flow to a tissue or organ and the additional insult sustained upon reperfusion that limits the amount of tissue that can be salvaged. IR injury plays a central role in both native and transplant acute kidney injury (AKI). Native AKI is associated with increased morbidity and mortality in hospital inpatients, and transplant AKI contributes to graft dysfunction, ultimately limiting graft longevity. In this review, we discuss the potential therapeutic benefits of a cost-effective and low-risk intervention, remote ischaemic preconditioning (RIPC), and its applicability in the prevention and reduction of AKI. [ABSTRACT FROM AUTHOR]

Summary objectives To examine the effect of hormone replacement therapy (HRT) on endothelial function of forearm resistance vessels in women with Turner’s syndrome. design Subjects were studied on three occasions: on their usual HRT (study 1), then after 6 weeks off HRT (study 2) and finally after a further 6 weeks on HRT (study 3). patients Seven young women with Turner’s syndrome were studied. measurements Forearm blood flow in response to intrabrachial infusion of bradykinin, 10, 30, 100 pmol/min (endothelium-dependent vasodilator), glyceryl trinitrate, 4, 8, 16 nmol/min (GTN; endothelium-independent vasodilator), noradrenaline, 60, 120, 240 pmol/min (NA, α-adrenergic receptor agonist) and NG -monomethyl-l-arginine, 1, 2, 4 µmol/min (L-NMMA; NO synthase inhibitor) was assessed by bilateral venous plethysmography. results The vasodilator response to bradykinin, expressed as the within-subject mean difference in area under the dose–response curve between study 2 and study 1, was significantly diminished (-744·2 ± 287·2, P = 0·04) but improved 6 weeks after HRT recommencement. However, there was no significant change in response to GTN (between study 2 and study 1, 189·5 ± 247·8, P = 0·47). The vasoconstrictor response to L-NMMA was also diminished in study 2 when compared to study 1 (-100·4 ± 35·4, P = 0·039) and was restored after HRT was recommenced (between study 3 and study 2, 117·5 ± 69·3, P = 0·17) whereas there was no significant difference in response to NA between study 2 and study 1 (76·7 ± 50·6, P = 0·18) or study 3 and study 2 (-70·8 ± 71·1, P = 0·38). conclusions HRT improves endothelial function in women with Turner’s syndrome. [ABSTRACT FROM AUTHOR]

The article presents an argumentation in response to the guidance issued by the National Institute for Health and Clinical Excellence (NICE) and the British Hypertension Society in Great Britain. They question the scope of the guidance in emphasizing the differences between drug classes and their combinations in blood pressure response and clinical outcomes. The further claims that while the simplification of drug choices and its classification could rest on price, tolerability and on specific contraindications, it will benefit healthcare commissioners, doctors, and patients.

Summary: Background: The cause of Crohn's disease has not been mechanistically proven. We tested the hypothesis that the disease is a form of immunodeficiency caused by impaired innate immunity. Methods: We investigated inflammatory responses in patients and controls by quantifying neutrophil recruitment and cytokine production after acute trauma, interleukin 8 secretion by cultured monocyte-derived macrophages after exposure to inflammatory mediators, and local inflammatory and vascular changes in response to subcutaneous injection of heat-killed Escherichia coli. Findings: In patients with Crohn's disease, trauma to rectum, ileum, or skin led to abnormally low neutrophil accumulation (differences from healthy individuals of 79%, n=8, p=0·0003; 57%, n=3, p=0·05; 50%, n=13, p<0·0001, respectively) and lower production of proinflammatory interleukin 8 (63%, n=7, p=0·003; 63%, n=3, p=0·05; 45%, n=8, p<0·0001) and interleukin 1β (50%, n=8, p=0·0005). Interleukin 8 secretion by cultured macrophages was reduced after exposure to acute wound fluid (38%, n=50, p<0·0001), C5a (48%, n=41, p=0·0005), or tumour necrosis factor α (52%, n=27, p<0·0001). Local inflammatory reaction to inoculation with E coli was attenuated, as quantified by changes in bloodflow (ileal disease 50%, n=6, p=0·01; colonic disease 77%, n=6, p=0·0003). This response was mediated by nitric oxide in controls, was increased by sildenafil in patients, and was not related to CARD15 genotype. Interpretation: In Crohn's disease, a constitutionally weak immune response predisposes to accumulation of intestinal contents that breach the mucosal barrier of the bowel wall, resulting in granuloma formation and chronic inflammation. Polymorphisms in CARD15 do not underlie this phenotype, but incapacitate the NOD2 pathway that can compensate for impairment of innate inflammation. Current treatment of secondary chronic inflammation might exaggerate the underlying lesion and promote chronic disease. [ABSTRACT FROM AUTHOR]

Background: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation.Methods: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss.Results: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min-1 (1.73 m)-2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]).Conclusions: RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia.Clinical Trial Registration: ISRCTN30083294. [ABSTRACT FROM AUTHOR]

Summary Background A consensus has emerged that angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARBs) have specific renoprotective effects. Guidelines specify that these are the drugs of choice for the treatment of hypertension in patients with renal disease. We sought to determine to what extent this consensus is supported by the available evidence. Methods Electronic databases were searched up to January, 2005, for randomised trials assessing antihypertensive drugs and progression of renal disease. Effects on primary discrete endpoints (doubling of creatinine and end-stage renal disease) and secondary continuous markers of renal outcomes (creatinine, albuminuria, and glomerular filtration rate) were calculated with random-effect models. The effects of ACE inhibitors or ARBs in placebo-controlled trials were compared with the effects seen in trials that used an active comparator drug. Findings Comparisons of ACE inhibitors or ARBs with other antihypertensive drugs yielded a relative risk of 0·71 (95% CI 0·49-1·04) for doubling of creatinine and a small benefit on end-stage renal disease (relative risk 0·87, 0·75-0·99). Analyses of the results by study size showed a smaller benefit in large studies. In patients with diabetic nephropathy, no benefit was seen in comparative trials of ACE inhibitors or ARBs on the doubling of creatinine (1·09, 0·55-2·15), end-stage renal disease (0·89, 0·74-1·07), glomerular filtration rate, or creatinine amounts. Placebo-controlled trials of ACE inhibitors or ARBs showed greater benefits than comparative trials on all renal outcomes, but were accompanied by substantial reductions in blood pressure in favour of ACE inhibitors or ARBs. Interpretation The benefits of ACE inhibitors or ARBs on renal outcomes in placebo-controlled trials probably result from a blood-pressure-lowering effect. In patients with diabetes, additional renoprotective actions of these substances beyond lowering blood pressure remain unproven, and there is uncertainty about the greater renoprotection seen in non-diabetic renal disease. [ABSTRACT FROM AUTHOR]