Francesca Calero

Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis

Background    No precise studies have been performed on cutaneous leukocytoclastic vasculitis (LV) to establish whether it is better to obtain a skin biopsy from lesional or from perilesional skin for direct immunofluorescence (DIF). There is no agreement on the immunoglobulins most frequently detected and the value of DIF for the classification of cutaneous vasculitis.

Albuminuria: más allá del riñón

Es clasica la asociacion de la proteinuria con la enfermedadrenal. De hecho, hasta no hace mucho, la proteinuria solose consideraba como el resultado de la enfermedad renalque produce un defecto en la barrera de filtracion que per-mitiria el paso de moleculas de mayor tamano. Actualmen-te, este concepto se ha ampliado de forma notable, y la pro-teinuria ha pasado a ser no solo marcador de enfermedadrenal, sino que se ha indicado su papel como mediador, oincluso como causa de progresion de la nefropatia. Asimis-mo, la proteinuria se considera hoy un marcador de eficaciaterapeutica renoprotectora del tratamiento con inhibidoresdel sistema renina-angiotensina (SRA).Mas alla del area nefrologica, se ha descrito, y tambien revi-sado en editoriales anteriores de esta revista, que no solo laproteinuria, sino pequenas cantidades de albumina urinaria(microalbuminuria), son marcadores sensibles de enferme-dad cardiovascular (ECV)

Central blood pressure variability is increased in hypertensive patients with target organ damage

We aimed to evaluate the association of aortic and brachial short‐term blood pressure variability (BPV) with the presence of target organ damage (TOD) in hypertensive patients. One‐hundred seventy‐eight patients, aged 57 ± 12 years, 33% women were studied. TOD was defined by the presence of left ventricular hypertrophy on echocardiogram, microalbuminuria, reduced glomerular filtration rate, or increased aortic pulse wave velocity. Aortic and brachial BPV was assessed by 24‐hour ambulatory BP monitoring (Mobil‐O‐Graph). TOD was present in 92 patients (51.7%). Compared to those without evidence of TOD, they had increased night‐to‐day ratios of systolic and diastolic BP (both aortic and brachial) and heart rate. They also had significant increased systolic BPV, as measured by both aortic and brachial daytime and 24‐hours standard deviations and coefficients of variation, as well as for average real variability. Circadian patterns and short‐term variability measures were very similar for aortic and brachial BP. We conclude that BPV is increased in hypertensive‐related TOD. Aortic BPV does not add relevant information in comparison to brachial BPV.

Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy

Urinary proteome was analyzed and quantified by tandem mass tag (TMT) labeling followed by bioinformatics analysis to study diabetic nephropathy (DN) pathophysiology and to identify biomarkers of a clinical outcome. We included type 2 diabetic normotensive non-obese males with (n = 9) and without (n = 11) incipient DN (microalbuminuria). Sample collection included blood and urine at baseline (control and DN basal) and, in DN patients, after 3 months of losartan treatment (DN treated). Urinary proteome analysis identified 166 differentially abundant proteins between controls and DN patients, 27 comparing DN-treated and DN-basal patients, and 182 between DN-treated patients and controls. The mathematical modeling analysis predicted 80 key proteins involved in DN pathophysiology and 15 in losartan effect, a total of 95 proteins. Out of these 95, 7 are involved in both processes. VCAM-1 and neprilysin stand out of these 7 for being differentially expressed in the urinary proteome. We observed an increase of VCAM-1 urine levels in DN-basal patients compared to diabetic controls and an increase of urinary neprilysin in DN-treated patients with persistent albuminuria; the latter was confirmed by ELISA. Our results point to neprilysin and VCAM-1 as potential candidates in DN pathology and treatment.

Cuff-Based Oscillometric Central and Brachial Blood Pressures Obtained Through ABPM are Similarly Associated with Renal Organ Damage in Arterial Hypertension

Background/Aims: Central blood pressure (BP) has been suggested to be a better estimator of hypertension-associated risks. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of renal organ damage in hypertensive patients. Methods: Brachial and central (calculated by an oscillometric system through brachial pulse wave analysis) office BP and ambulatory BP monitoring (ABPM) data and aortic pulse wave velocity (PWV) were measured in 208 hypertensive patients. Renal organ damage was evaluated by means of the albumin to creatinine ratio and the estimated glomerular filtration rate. Results: Fifty-four patients (25.9%) were affected by renal organ damage, displaying either microalbuminuria (urinary albumin excretion ≥30 mg/g creatinine) or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Compared to those without renal abnormalities, hypertensive patients with kidney damage had higher values of office brachial systolic BP (SBP) and pulse pressure (PP), and 24-h, daytime, and nighttime central and brachial SBP and PP. They also had a blunted nocturnal decrease in both central and brachial BP, and higher values of aortic PWV. After adjustment for age, gender, and antihypertensive treatment, only ABPM-derived BP estimates (both central and brachial) showed significant associations with the presence of renal damage. Odds ratios for central BP estimates were not significantly higher than those obtained for brachial BP. Conclusion: Compared with peripheral ABPM, cuff-based oscillometric central ABPM does not show a closer association with presence of renal organ damage in hypertensive patients. More studies, however, need to be done to better identify the role of central BP in clinical practice.

[PP.07.06] URINARY PROTEOME ANALYSIS IDENTIFIED NEPRILYSIN AND VCAM AS KEY PROTEINS IN THE DEVELOPMENT OF DIABETIC NEPHROPATHY

Objective: Diabetic nephropathy (DN) is the major cause of end-stage renal disease. Renin-angiotensin system (RAS) inhibition is the preferred treatment to slow its progression. We have studied the urinary proteomes of patients with DN (high albuminuria) to investigate the pathophysiology of renal disease and identify disease markers and predictors of clinical outcome. Design and method: We included diabetic men with (n = 9) and without DN (n = 12) (control cohort). Data collection included clinical and laboratory evaluation of blood and urine at baseline (control cohort and DN-basal), and in patients with DN after 3 months of losartan treatment (DN-treated). Urinary proteome was analyzed and quantified by Tandem Mass Tag (TMT) labeling on a LTQ-Orbitrap mass spectrometer. Results: Patients enrolled in the study showed no differences regarding basic clinical parameters. Urinary proteome analysis have identified 166 differentially excreted proteins when comparing the proteomes of controls and DN patients, 27 comparing DN-treated and DN-basal patients, and 182 among patients DN-treated and controls. Systems biology approach comprising functional proteomic networks and artificial neural networks (TPMS technology) have identified 80 key proteins involved in the pathophysiology of DN and 15 key proteins involved in the efficacy of losartan. There are 7 proteins identified in the urine proteome that are essential in both DN pathophysiology and treatment efficacy. Vascular cell adhesion molecule-1 (VCAM-1) and the angiotensin-metabolizing neutral endopeptidase neprilysin (NEP) stand out from the other identified proteins because they are the only ones that are DN effectors. They are differentially expressed in the urinary proteome and are also key proteins in both DN pathophysiology and RAS inhibition efficacy. Conclusions: NEP is a membrane-bound zinc-containing metalloproteinase showing great abundance in the brush border of proximal renal tubular cells. NEP is responsible for the processing and catabolism of several vasoactive peptides including angiotensin II and endothelin which may explain its pathogenic role in the development of DN.