The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. Methods: We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Results: Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. Conclusions: DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia: the ANGIOCOR prospective cohort study protocol.

BACKGROUND: Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. METHODS: Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. DISCUSSION: The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. TRIAL REGISTRATION: NCT04162236.

Risk factors for non-diabetic renal disease in diabetic patients.

BACKGROUND: Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. METHODS: Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. RESULTS: In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P < 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. CONCLUSIONS: The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.

Association of Either Left Ventricular Hypertrophy or Diastolic Dysfunction With 24-Hour Central and Peripheral Blood Pressure.

BACKGROUND: Central blood pressure (BP) is considered as a better estimator of hypertension-associated risks than peripheral BP. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of left ventricular hypertrophy (LVH), or diastolic dysfunction (DD). METHODS: The cross-sectional study consisted of 208 hypertensive patients, aged 57 ± 12 years, of which 34% were women. Office and 24-hour central and peripheral BP were measured by the oscillometric Mobil-O-Graph device. We performed echocardiography-Doppler measurements to calculate LVH and DD, defined as left atrium volume ≥34 ml/m2 or septal e' velocity <8 cm/s or lateral e' velocity <10 cm/s. RESULTS: Seventy-seven patients (37%) had LVH, and 110 patients (58%) had DD. Systolic and pulse BP estimates (office, 24-hour, daytime, and nighttime) were associated with the presence of LVH or DD, after adjustment for age, gender, and antihypertensive treatment, with higher odds ratios for ambulatory-derived values. The comparison between central and peripheral BP estimates did not reveal a statistically significant superiority of the former neither in multiple regression models with simultaneous adjustments nor in the comparison of areas under receiver-operating curves. Correlation coefficients of BP estimates with left ventricular mass, although numerically higher for central BP, did not significantly differ between central and peripheral BP. CONCLUSIONS: We have not found a significant better association of 24-hour central over peripheral BP, with hypertensive cardiac alterations, although due to the sample size, these results require further confirmation in order to assess the possible role of routine 24-hour central BP measurement.

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.

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.

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.

Twenty-four-hour central blood pressure is not better associated with hypertensive target organ damage than 24-h peripheral blood pressure.

BACKGROUND AND AIM: Central blood pressure (BP) is increasingly considered as a better estimator of hypertension associated risks. We aimed to evaluate the association of 24-h central BP, in comparison with 24-h peripheral BP, with the presence of target organ damage (TOD). METHODS: Cross-sectional study of 208 hypertensive patients, aged 57 ±â€Š12 years, 34% women. Office (mean of 4 measurements) and 24-h central and peripheral BP were measured by the oscillometric Mobil-O-Graph device. TOD was assessed at cardiac (left ventricular hypertrophy by echocardiography), renal (reduction of glomerular filtration rate and/or microalbuminuria), and arterial (increased aortic pulse wave velocity) levels. RESULTS: A total of 107 patients (51.4%) had TOD (77, 35% patients left ventricular hypertrophy; 54, 25.9% renal abnormalities; and 40, 19.2% arterial stiffness). All SBP and pulse BP estimates (office, 24-h, daytime, and night-time) were associated with the presence of TOD, after adjustment for age, sex, and antihypertensive treatment, with higher odds ratios for ambulatory-derived values. Odds ratios for central and peripheral BP were similar for all office, 24-h, daytime, and night-time BP. After simultaneous adjustment, peripheral, but not central, 24-h and night-time SBP and pulse pressures were associated with the presence of TOD. CONCLUSION: TOD in hypertension is associated with BP elevation, independently of the type of measurement (office or ambulatory, central or peripheral). Central BP, even monitored during 24 h, is not better associated with TOD than peripheral BP. These results do not support a routine measurement of 24-h central BP.

Albuminuria: más allá del riñón / Albuminuria: beyond the kidney

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Treatment of idiopathic membranous nephropathy with the combination of steroids, tacrolimus and mycophenolate mofetil: results of a pilot study.

BACKGROUND: Membranous nephropathy is a common cause of nephrotic syndrome (NS) in adults. Its treatment is still under debate. METHODS: We report our experience in a pilot study using initially low doses of steroids and tacrolimus (Tac). After 3 months of treatment, mycophenolate mofetil (MMF) was added if the proteinuria was higher than 1 g/day. RESULTS: In accordance with this standard, 21 patients entered the study. A proteinuria level lower than 1 g/day was reached at month 3 of therapy with steroids and Tac in 11 patients. These patients continued this treatment for 12 months. MMF was added in nine cases after the third month and triple therapy was maintained for 12 more months. Two patients were withdrawn because of side effects. At the end of the treatment, remission of the NS was present in 15 out of all the patients (71.4%). Remission of the NS was complete in eight (53.3%) patients and partial in seven (46.7%) others. The remaining four patients did not respond. There were no significant changes in renal function. At a mean time of 23.1 months after treatment was discontinued, 11 (73.3%) patients had relapsed. CONCLUSIONS: In this trial, treatment with tacrolimus showed a good efficacy but a high relapse rate when it was discontinued.

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. METHODS: A prospective study of DIF in lesional and perilesional skin was performed in 50 leukocytoclastic vasculitis patients and 15 nonvasculitis patients. RESULTS: We detected a higher level of positivity in involved skin than in uninvolved skin for IgG, IgA, IgM, C3 and fibrinogen but not for C1q. In vasculitic patients, IgA was the immunoglobulin most frequently detected in lesional (82%) and perilesional skin (68%), followed by IgM (56 and 34%, respectively) and IgG (20 and 8%, respectively). Only IgA deposits were associated with the diagnosis of vasculitis, with a sensitivity of 82% in lesional and 68% in perilesional skin, and with a specificity of 73 and 66.7%, respectively. The presence of IgA in lesional skin was associated with renal involvement but there was no association with severity. The presence of IgG or IgM, or the absence of IgA in perilesional skin was related to the presence of cryoglobulins. The absence of IgA in lesional and perilesional skin was also related to hepatitis C virus infection. CONCLUSIONS: DIF findings in involved skin are more closely related to the diagnosis of vasculitis and can give more information about overall renal involvement than findings in uninvolved skin. However, findings in uninvolved skin are more closely related to the pathogenic factors that trigger the development of vasculitis.