Circulating genotypes of Toxoplasma gondii in Northwestern Italy.

Toxoplasma gondii is an apicomplexan parasite that in Europe is genetically characterized by three main clonal genotypes, with a lesser prevalence of atypical patterns. Data on the genotypes of T. gondii circulating both in wildlife and livestock in Northern Italy are scarce. In the present study skeletal muscle samples of cattle (Bos taurus), swine (Sus scrofa domesticus), fox (Vulpes vulpes), roe deer (Capreolus capreolus) and wild boar (Sus scrofa) were genotyped by using a nested PCR of 6 loci (alt.SAG2, GRA6, 5'SAG2, BTUB, C22-8 and SAG1) and in silico RFLP. High prevalence of genotype I and non-canonical genotypes were observed in this study, with some differences in the population structure of the parasite between livestock and wildlife. Genetic variability of T. gondii in Europe could be more variable than previously thought, with possible implication for public health.

Preventing microalbuminuria in type 2 diabetes.

BACKGROUND: The multicenter double-blind, randomized Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) was designed to assess whether angiotensin-converting-enzyme inhibitors and non-dihydropyridine calcium-channel blockers, alone or in combination, prevent microalbuminuria in subjects with hypertension, type 2 diabetes mellitus, and normal urinary albumin excretion. METHODS: We studied 1204 subjects, who were randomly assigned to receive at least three years of treatment with trandolapril (at a dose of 2 mg per day) plus verapamil (sustained-release formulation, 180 mg per day), trandolapril alone (2 mg per day), verapamil alone (sustained-release formulation, 240 mg per day), or placebo. The target blood pressure was 120/80 mm Hg. The primary end point was the development of persistent microalbuminuria (overnight albumin excretion, > or =20 microg per minute at two consecutive visits). RESULTS: The primary outcome was reached in 5.7 percent of the subjects receiving trandolapril plus verapamil, 6.0 percent of the subjects receiving trandolapril, 11.9 percent of the subjects receiving verapamil, and 10.0 percent of control subjects receiving placebo. The estimated acceleration factor (which quantifies the effect of one treatment relative to another in accelerating or slowing disease progression) adjusted for predefined baseline characteristics was 0.39 for the comparison between verapamil plus trandolapril and placebo (P=0.01), 0.47 for the comparison between trandolapril and placebo (P=0.01), and 0.83 for the comparison between verapamil and placebo (P=0.54). Trandolapril plus verapamil and trandolapril alone delayed the onset of microalbuminuria by factors of 2.6 and 2.1, respectively. Serious adverse events were similar in all treatment groups. CONCLUSIONS: In subjects with type 2 diabetes and hypertension but with normoalbuminuria, the use of trandolapril plus verapamil and trandolapril alone decreased the incidence of microalbuminuria to a similar extent. The effect of verapamil alone was similar to that of placebo.

Vascular access-related thrombotic complications: research hypotheses and therapeutic strategies.

The most common complication of permanent vascular access is thrombosis, which accounts for 80 to 85% of AV access loss. Treatment of venous stenosis by percutaneous angioplasty, endovascular stents and surgical revision is clinically important but many strategies to prevent thrombosis have been employed, such as antiplatelet agents, systemic anticoagulation, and experimental therapies as fish oils, heparinoids, clopidogrel, renin-angiotensin system antagonists, calcium channel blockers, alpha adrenergic antagonists, homocysteine-lowering agents and beta-hydroxybetamethyglutaryl coenzyme-A reductase inhibitors. Future but promising approaches are endovascular radiation and gene therapy.

Emerging drugs for diabetic nephropathy.

There is an increasing number of patients with diabetes mellitus in many countries. Diabetic kidney disease, one of its microvascular complications, is also increasing markedly and has become a major cause of end stage renal disease worldwide. Intervention for preventing and delaying the development and progression of diabetic kidney disease is not only a medical concern, but also a social issue. Despite extensive efforts, however, medical interventions thus far are not effective enough to prevent the progression of the disease and the development of end stage renal disease. This justifies attempts to develop novel therapeutic approaches for diabetic nephropathy. Recent insights on its pathogenesis and progression have suggested new targets for the specific treatment of this disease. They include aldosterone, aldose reductase, arachidonic acid metabolites, growth factors, advanced glycosylation end-products, peroxisome proliferator-activated receptors and endothelin. Several other biochemical mediators have been targeted in experimental animal models with the goal to prevent diabetic nephropathy progression, but translation to clinics of these experimental achievements are still limited or lacking.

Doppler ultrasonography in posttransplant renal artery stenosis: a reliable tool for assessing effectiveness of revascularization?

BACKGROUND: Renal artery stenosis is usually treated by angioplasty and stenting, but the effectiveness of graft perfusion is difficult to establish on clinical grounds. METHODS: We compared changes in Doppler ultrasound parameters such as resistive index and peak systolic velocity with concomitant changes in renal vascular resistances, renal blood velocity, and wall shear stress measured before and 1 month after percutaneous transluminal angioplasty and stenting in 12 renal transplant patients with renal artery stenosis. RESULTS: After revascularization, peak systolic velocity and resistive index normalized in all patients. Changes in peak systolic velocity (-72%; P<0.001 vs. basal) were positively correlated (P<0.0001; r=0.87) with those in renal blood velocity (-88%; P<0.01 vs. basal) and with those (P<0.0005; r=0.80) in wall shear stress (-97%; P<0.005). Changes in resistive index (+21%; P<0.005) were negatively correlated (P=0.009; r=0.51) with those in renal vascular resistances (-40%; P<0.01). Changes in Doppler parameters (resistive index and peak systolic velocity) reflected those in renal vascular resistances and renal blood velocity with 100% sensitivity and specificity. CONCLUSIONS: Doppler ultrasound is a reliable, noninvasive, and easily available tool for identifying subjects who may benefit from kidney graft revascularization and to assess the effectiveness of the procedure.

Radial artery remodeling in response to shear stress increase within arteriovenous fistula for hemodialysis access.

It is known that changes in blood flow induce vascular remodeling and that shear stress, the tractive force acting on the vessel wall due to blood flowing, influences endothelial cell function. The aim of the present study was to investigate the relation between changes in pulsatile shear forces and arterial remodeling in response to chronic elevation in blood flow within the radial artery. The authors studied vessel diameter, flow rate, and shear stress in the radial artery of uremic patients before and after surgical creation of a native arteriovenous fistula for hemodialysis access. For this purpose, the authors used echo-color-Doppler ultrasound to perform diameter and blood velocity measurements. Time-function blood flow rate and wall shear stress were calculated based on arterial diameter, center-line velocity wave-form, and blood viscosity, using a numerical method developed according to Womersley's theory for unsteady flow in tubes. The results confirmed that the radial artery diameter increases in response to a chronic increase in blood flow in uremic patients. Moreover, it seems that the radial artery dilates in such a way as to maintain the peak wall shear stress constant, suggesting that endothelial cells sense the maximum rather than the time-averaged wall shear stress. This finding may lead to further understanding of the mechanisms responsible for endothelial response to physical stimulation by flowing blood.

Radial artery wall shear stress evaluation in patients with arteriovenous fistula for hemodialysis access.

It has been extensively documented that changes in blood flow induce vascular remodeling and this phenomenon seems to be correlated to the shear forces imposed on the vessel wall by motion of blood. Wall shear stress, the tractive force that acts on the endothelium, has been shown to influence endothelial cell function. To study changes in wall shear stress that develop on the vessel wall upon changes of blood flow, we set up a technique that allows estimation of shear stress in the radial artery of patients on chronic hemodialysis therapy. The technique is based on color-flow Doppler examination of the radial artery before and after surgical creation of radiocephalic fistula for hemodialysis. Calculation of time function wall shear stress and blood flow rate in the radial artery is performed on the basis of arterial diameter, center-line velocity waveform and blood viscosity, using a numerical method developed according to Womersley's theory for pulsatile flow in tubes. The results presented confirm that the model developed is suitable for calculation of the wall shear stress that develops in the radial artery of patients before and after surgical creation of an arteriovenous fistula for hemodialysis. This methodology was developed for characterization of wall shear stress in the radial artery but may be well applied to other vessels that can be examined by echo-Doppler technique.

Acute kidney injury in a preterm infant homozygous for the C3435T polymorphism in the ABCB1 gene given oral morphine.

A 34-week infant born from a mother with a history of drug abuse developed neonatal abstinence syndrome (NAS) in the first hours of life. Urine drug screening was positive for cocaine and heroin. The infant developed acute kidney injury and bilateral hydronephrosis while receiving oral morphine for control of NAS. Cessation of morphine therapy and urinary catheterization resulted in a rapid and complete resolution of the symptoms. Our patient was homozygous for the C3435T polymorphism in the ABCB1 gene, a polymorphism previously associated with impaired P-glycoprotein activity. We hypothesize that acute renal toxicity was related to accumulation of morphine within urothelial cells due to genetically determined impaired P-glycoprotein activity.

Computed tomography evaluation of autosomal dominant polycystic kidney disease progression: a progress report.

At the moment, there are no effective therapies to prevent or slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Radiologic evaluations are used to monitor volume of renal cysts and parenchyma during disease evolution. Volumetric quantifications based on computed tomography were used to investigate the relation between structural and functional changes in patients with advanced-stage ADPKD. By use of image-processing techniques, volume of kidneys, renal cysts, fully enhanced parenchyma, and faintly contrast-enhanced parenchyma, referred to as intermediate, was estimated. GFR measurements and computed tomography evaluations were repeated 6 mo later. No statistically significant correlations were found between volumes of cysts and parenchyma and intermediate volume and GFR. However, the ratio of intermediate over parenchymal volume strongly correlated with GFR (r = -0.81, P < 0.001). In addition, there were significant correlations between percentage changes in intermediate volume (absolute or relative to parenchyma) and GFR changes during the observation period (r = -0.70 and r = -0.75, P < 0.01). These data support the hypothesis of a significant relation between radiologic appearance of renal structure and functional changes and suggest new ways that renal dysfunction in ADPKD may be predicted. Further work is necessary to determine the nature of faintly contrast-enhanced parenchyma and its role in renal functional loss.

Transplant renal artery stenosis.

Transplant renal artery stenosis (TRAS) is a recognized, potentially curable cause of posttransplant arterial hypertension, allograft dysfunction, and graft loss. It usually occurs 3 mo to 2 yr after transplantation, but early or later presentations are not uncommon. The prevalence ranges widely from 1 to 23% in different series, reflecting the heterogeneous criteria used to establish the diagnosis, the different manner of preservation of the graft, and surgical expertise. Reported cases are progressively increasing in parallel with the use of non-invasive investigation procedures, such as Doppler ultrasonography and magnetic resonance (MR) angiography, that arouse the suspicion of the disease even in less symptomatic cases. However, definitive diagnosis of hemodynamically significant stenosis rests on the use of invasive angiographic techniques. Percutaneous transluminal angioplasty (PTA) is the treatment of choice and restores kidney perfusion in 60 to 90% of cases. The risk of re-stenosis, the major drawback of the procedure, is prevented by the use of expandable endoprostheses. Surgery is indicated for stenoses that cannot be treated by PTA or that recur after it. Doppler ultrasonography is the procedure of choice to evaluate graft perfusion before and after revascularization.