We studied the non-obese diabetic (NOD) mice model because it develops autoimmune diabetes that resembles human type 1 diabetes. In diabetic mice, urinary albumin excretion (UAE) was ten-fold ...increased at an "early stage" of diabetes, and twenty-fold increased at a "later stage" (21 and 40 days, respectively after diabetes diagnosis) as compared to non-obese resistant controls. In NOD Diabetic mice, glomerular enlargement, increased glomerular filtration rate (GFR) and increased blood pressure were observed in the early stage. In the late stage, NOD Diabetic mice developed mesangial expansion and reduced podocyte number. Circulating and urine ACE2 activity were markedly increased both, early and late in Diabetic mice. Insulin administration prevented albuminuria, markedly reduced GFR, blood pressure, and glomerular enlargement in the early stage; and prevented mesangial expansion and the reduced podocyte number in the late stage of diabetes. The increase in serum and urine ACE2 activity was normalized by insulin administration at the early and late stages of diabetes in Diabetic mice. We conclude that the Diabetic mice develops features of early kidney disease, including albuminuria and a marked increase in GFR. ACE2 activity is increased starting at an early stage in both serum and urine. Moreover, these alterations can be completely prevented by the chronic administration of insulin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Migraine is a leading cause of disability, estimated to affect one-in-ten people in Spain. This study aimed to describe the management of migraine in Spain and identify improvement areas.
...Non-interventional, retrospective, cross-sectional cohort study conducted using an electronic medical records database covering visits to public healthcare providers for 3% of the Spanish population. Patients with a migraine diagnosis (ICD-9 346) between 01/2015 and 04/2022 were included, as well as their demographic and clinical characteristics, prescribed migraine treatments and the specialty of the prescribing physicians.
The database included 61,204 patients diagnosed with migraine. A migraine treatment had been prescribed to 50.6% of patients over the last 24 months (only acute to 69.5%, both acute and preventive to 24.2%, and only preventive to 6.3%). The most frequently prescribed treatments were NSAIDs (56.3%), triptans (44.1%) and analgesics (28.9%). Antidepressants were the most common preventive treatment (prescribed to 17.9% of all treated patients and 58.7% of those treated with a preventive medication), and anti-CGRP monoclonal antibodies the least prescribed (1.7%; 5.7%). In 13.4% of cases, preventive medications were the first treatment: alone in 5.8% of cases and together with an acute medication in 7.6%. A fifth of patients who were initially prescribed with only acute treatment were later prescribed a preventive medication (20.7%). On average, it took 29.4 months for this change to occur. Two-thirds of patients started their preventive treatment in primary care (64.2%). The percentage of patients treated by a neurologist increased with the number of received preventive medications. However, 28.8% of patients who had already been prescribed five or more distinct preventive treatments were not treated by a neurologist. Migraine patients had between 1.2- and 2.2-times higher prevalence of comorbidities than the general population, age-gender adjusted.
Our study emphasizes the need for improved management of migraine in Spain to reduce the risk of chronification and improve patient outcomes. More training and coordination across healthcare professionals is necessary to recognize and address risk factors for migraine progression, including multiple associated comorbidities and several lines of treatment, and to provide personalized treatment plans that address the complex nature of the condition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Correlation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of ...undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved.
We retrospectively assessed patients with transplant biopsies scored following Banff'15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies MICA-Ab, angiotensin-II type-1-receptor (AT
R)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM). We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMR
) with and without HLA-DSA.
One-hundred eighteen patients with normal histology (n = 19), ABMR
(n = 52) or IFTA (n = 47) were studied. ABMR
patients were HLA-DSA
(n = 38, 73%) or HLA-DSA
(n = 14, 27%). Pre-transplant HLA-DSA and AT
R-Ab were more frequent in ABMR
compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMR
DSA
cases showed non-HLA antibodies. ABMR
DSA
and ABMR
DSA
cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMR
DSA
but not with ABMR
DSA
. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 1.31-10.37, p = 0.013) and AT
R-Ab (OR: 5.47 1.78-16.76, p = 0.003) were independent predictors of ABMR
DSA
.
In conclusion, pre-transplant AT
R-Ab is frequently found in ABMR
DSA
patients. However, AT
R-Ab, MICA-Ab, ETAR-Ab or EC-XM
are rarely found among ABMR
DSA
patients. Pre-transplant AT
R-Ab may act synergistically with preformed or
HLA-DSA to produce ABMR
DSA
but not ABMR
DSA
. HLA epitope mismatch associates with ABMR
DSA
compared with ABMR
DSA
, suggesting factors other than HLA are responsible for the damage.
ObjectivesDevelopment of pharmaceutical agents in transplantation is currently limited by long waits for hard endpoints. We applied a validated integrative risk-prognostication system integrative Box ...(iBox) as a surrogate endpoint to the TRANSFORM Study, a large randomised controlled trial, to project individual patient long-term kidney allograft survival from 1 year to 11 years after randomisation.DesignPost-hoc analysis of a randomised open-label controlled trial.SettingMulticentre study including 186 centres in 42 countries worldwide.Participants2037 de novo kidney transplant recipients.InterventionParticipants were randomised (1:1) to receive everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) or mycophenolic acid with standard-exposure CNI (MPA+sCNI).Primary outcome measureThe iBox scores were computed for each participant at 1 year after randomisation using functional, immunological and histological parameters. Individual long-term death-censored allograft survival over 4, 6 and 11 years after randomisation was projected with the iBox risk-prognostication system.ResultsOverall, 940 patients receiving EVR+rCNI and 932 receiving MPA+sCNI completed the 1-year visit. iBox scores generated at 1 year yielded graft survival prediction rates of 90.9% vs 92.1%, 87.9% vs 89.5%, and 80.0% vs 82.4% in the EVR+rCNI versus MPA+sCNI arms at 4, 6, and 11 years post-randomisation, respectively (all differences below the 10% non-inferiority margin defined by study protocol). Inclusion of immunological and histological Banff diagnoses parameters in iBox scores resulted in comparable and non-inferior predicted graft survival for both treatments.ConclusionsThis proof-of-concept study provides the first application of a validated prognostication system as a surrogate endpoint in the field of transplantation. The iBox system, by projecting kidney allograft survival up to 11 years post-randomisation, confirms the non-inferiority of EVR+rCNI versus MPA+sCNI regimen. Given the current process engaged for surrogate endpoints qualification, this study illustrates the potential to fast track development of pharmaceutical agents.Trial registration numberTRANSFORM trial: NCT01950819.iBox prognostication system: NCT03474003.
Two technology opportunities, integration of renewable energy sources and the electrification of vehicles are being encouraged to reduce dependency on fossil fuels and pollution problems. ...Nevertheless, the huge increase of plug-in hybrid electric vehicles (PHEVs) on roads will cause an additional load in demand, especially at rush hours, and therefore, threatens the stability of existing power grids. Considering PHEV stay for several hours in the workplace, (i.e., university), this may provide an inimitable framework to charge PHEV from wind in the workplace. This paper introduces the possibility of introducing intelligent control of wind power and battery storage units as supplementary power sources for future PHEV charging demands during rush hours. The operation of the proposed algorithm is based on the priority levels of PHEVs charging, and fluctuations in DC link voltage levels due to the variation in wind speed. The priorities of PHEVs charging are developed according to their power requirements, maximum rating of distribution transformer and park duration of PHEVs in the workplace during wind speed. Various non-isolated proportional–integral controllers and improved intelligent fuzzy control are used to keep a minimum critical DC link voltage to permit the power conditioning system to operate a charging station uninterruptedly, even at low wind speed. The improved intelligent fuzzy controller also contributes to minimizing the stress on the DC bus and ensures quality output power. The performance of the proposed charging station is verified for the real PHEV under real-world record of wind speed. All the energy sources, electric charging station and their controllers are designed in MATLAB/Simulink. Finally, the feasibility of proposed charging station is checked experimentally in the laboratory.
Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals ...from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.
Resistant hypertension (RH) represents an important multi-organic impact and increases the morbi-mortality. We aimed to evaluate the evolution of hypertensive mediated organ damage in patients with ...RH after adding spironolactone.
Retrospective study of 58 patients with RH who started spironolactone (12.5–25mg daily). Office blood pressure, 24-h ambulatory blood pressure monitoring (24h-ABPM), urine albumin-to-creatinine ratio and echocardiographic parameters were analyzed prior to initiation of spironolactone and after 12 months of treatment.
Thirty-six percent of patients were women and mean age was 67.3±10.1 years. We observed a decrease in urine albumin-to-creatinine ratio (median RIQ25–75) of 27.0 (7.5–255.4) to 11.3 (3.1–37.8)mg/g, p=0.009. This was more relevant in patients with albuminuria grade A2 and A3: 371.2 (139.5–797.4) to 68.4 (26.5–186.5)mg/g, p=0.02. The echocardiographic changes were: posterior wall thickness: −1.0±0.4mm (p<0.001), interventricular septal thickness: −0.6±0.5mm (p=0.01), left ventricular (LV) mass index: −14.7±10.2g/m2 (p=0.006), LV remodeling index: −0.04±0.036 (p=0.03), without statistically significant changes in LV ejection fraction, LV end-diastolic diameter, LV end-systolic diameter, left atrial diameter, relationship between early ventricular filling wave and atrial contraction and LV filling pressure index.
Systolic/diastolic office blood pressure decreased −12.5±4.9/−4.9±3.0mmHg, p<0.001. In 24h-ABPM, systolic and diastolic BP had a significant decrease in diurnal and nocturnal periods and 38.1% of patients presented a favorable change in the circadian pattern, p<0.001.
Adding spironolactone to patients with RH contributes to improve hypertensive mediated organ damage by reducing albuminuria levels and echocardiographic parameters of hypertensive heart disease.
La hipertensión arterial resistente (HTAR) supone un importante impacto a nivel multiorgánico e incrementa la morbimortalidad. Este trabajo evalúa la evolución de la lesión orgánica mediada por hipertensión en pacientes con HTAR tras añadir espironolactona.
Estudio retrospectivo de 58 pacientes con HTAR a quienes se añadió espironolactona (12,5–25mg/día). Se obtuvieron parámetros de presión arterial clínica y MAPA-24h, cociente albúmina/creatinina y datos ecocardiográficos previos a iniciar espironolactona y tras 12 meses de tratamiento.
El 36,2% de los pacientes eran mujeres y la edad media de 67,3±10,1 años. Se objetivó un descenso en albuminuria (mediana RIC25–75) de 27,0 (7,5–255,4) a 11,3 (3,1–37,8)mg/g (p=0,009), siendo más marcado en pacientes con albuminuria grado A2 y A3: de 371,2 (139,5–797,4) a 68,4 (26,5–186,5)mg/g, p=0,02.. A nivel ecocardiográfico se evidenció: pared posterior: −1,0±0,4mm (p<0,001), tabique interventricular: −0,6±0,5mm (p=0,01), índice de masa del ventrículo izquierdo (VI): −14,7±10,2 g/m2 (p=0,006), índice de remodelado del VI: −0,04±0,036 (p=0,03), sin cambios estadísticamente significativos en fracción de eyección VI, diámetro diastólico VI, diámetro sistólico VI, diámetro de aurícula izquierda, relación entre onda de llenado ventricular temprano y contracción auricular ni en índice de presión llenado VI.
La presión arterial clínica sistólica/diastólica presentó un descenso de −12,5±4,9/−4,9±3,0mmHg, p<0,001. En los MAPA-24h se observó un descenso significativo de presión arterial sistólica y diastólica en los períodos diurno y nocturno, y un cambio favorable en el patrón circadiano en el 38,1% de los pacientes, p<0,001.
Añadir espironolactona en HTAR contribuye a la reducción de la lesión orgánica mediada por hipertensión a nivel de albuminuria y de parámetros ecocardiográficos de cardiopatía hipertensiva.
Acute kidney injury (AKI) is a life-threatening complication of severe rhabdomyolysis. This study was conducted to assess risk factors for AKI and to develop a risk score for early prediction.
...Retrospective observational cohort study with a 9-year follow-up, carried out in an acute-care teaching-affiliated hospital. A total of 126 patients with severe rhabdomyolysis defined as serum creatine kinase (CK) > 5,000 IU/L fulfilled the inclusion criteria. Univariate and logistic regression analyses were performed to determine risk factors for AKI. Based on the values obtained for each variable, a risk score and prognostic probabilities were estimated to establish the risk for developing AKI.
The incidence of AKI was 58%. Death during hospitalization was significantly higher among patients with AKI, compared to patients without AKI (19.2% vs 3.6%, p = 0.008). The following variables were independently associated with AKI: peak CK (odds ratio OR 4.9, 95%CI 1.4-16.8), hypoalbuminemia (< 33 mg/dL, OR 5.1, 95%CI 1.4-17-7), metabolic acidosis (OR 5.3, 95%CI 1.4-20.3), and decreased prothrombin time (OR 4.4, 95% CI 1.3-14.5). A risk score for AKI was calculated for each patient, with an OR of 1.72 (95%CI 1.45-2.04). The discrimination value of the predictive model was established by means of a ROC curve, with the area under the curve of 0.871 (p<0.001).
The identification of independent factors associated with AKI and a risk score for early prediction of this complication in patients with severe rhabdomyolysis may be useful in clinical practice, particularly to implement early preventive measures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with chronic kidney disease. The issue of ESA safety has been raised in multiple studies, with correlates derived ...for elevated cancer incidence and mortality. Whether these associations are related to ESA dose or the typology of the patient remains obscure.
A multicentre, observational retrospective propensity score-matched study was designed to analyse the effects of weekly ESA dose in 1679 incident haemodialysis (HD) patients. ESA administration was according to standard medical practice. Patients were grouped as quintiles, according to ESA dose, in order to compare mortality and hospitalization data. Using propensity score matching (PSM), we defined two groups of 324 patients receiving weekly threshold ESA doses of either > or ≤8000 IU.
Kaplan-Meier survival curves indicated significant increases in the risk of mortality in patients administered with high doses of ESAs (>8127.4 IU/week). Multivariate Cox models identified a high ESA dose as an independent predictor for all-cause and cardiovascular (CV) mortality. Moreover, logistic regression models identified high ESA doses as an independent predictor for all-cause, CV and infectious hospitalization. PSM analyses confirmed that weekly ESA doses of >8000 IU constitute an independent predictor of all-cause mortality and hospitalization, even though the adjusted cohort displayed the same demographic features, inflammatory profile, clinical HD parameters and haemoglobin levels.
Our data suggest that ESA doses of >8000 IU/week are associated with an increased risk of all-cause mortality and hospitalization in HD patients.
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