Statins stabilize the renal function of IgA nephropathy

Background: The renoprotective pleiotropic effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has recently been reported by several investigators. However, the effect of statins on IgA nephropathy (IgAN) is still unknown. Methods: We selected 24 IgAN patients who had newly started statin therapy and were not treated with steroids and immunosuppressive agents during the observation period. We analyzed and compared clinical findings 1 year before and after treatment. Results: Mean age was 50.5?±?9.91 years and mean blood pressure was 90.9?±?10.8?mmHg. Renal function was slightly deteriorated, serum creatinine was 1.03 (0.71–1.24) mg/dL and estimated glomerular filtration rate (eGFR) was 55.8?±?22.8?mL/min. Lipid metabolism was poorly controlled [total cholesterol 247.7?±?35.7?mg/dL, low-density lipoprotein cholesterol 151.5 (140.8–172.8) mg/dL, and triglyceride 163.0 (126.3–243.8) mg/dL]. Mild urinary abnormality was observed [proteinuria: 0.50 (0.22–1.29) g/g creatinine, urinary red blood cells 1.0 (0.2–5.0) per high power field]. After 1 year of statin treatment, lipid control was significantly better than at baseline. Proteinuria was not significantly decreased but renal function was improved. eGFR changed from a ?5.9% decrease to a 2.4% increase (p?=?0.0098). Conclusion: Our results indicated that statins stabilized the renal function of IgAN patients independent of their reduction of proteinuria.     

Urinary protein and renal prognosis in idiopathic membranous nephropathy: a multicenter retrospective cohort study in Japan

Background: Several studies have revealed a relationship between proteinuria and renal prognosis in idiopathic membranous nephropathy (IMN). The benefit of achieving subnephrotic proteinuria (<3.5?g/day), however, has not been well described.

Methods: This multicenter, retrospective cohort study included 171 patients with IMN from 10 nephrology centers in Japan. The relationship between urinary protein over time and a decrease of 30% in estimated glomerular filtration rate (eGFR) was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors.

Results: During the observation period (median, 37?months; interquartile range, 16–71?months), 37 (21.6%) patients developed a 30% decline in eGFR, and 2 (1.2%) progressed to end-stage renal disease. Time-dependent multivariate Cox regression models revealed that lower proteinuria over time were significantly associated with a lower risk for a decrease of 30% in eGFR (primary outcome), adjusted for clinically relevant factors. Complete remission (adjusted hazard ratio [HR], 0.005 [95%CI, 0.0–0.09], p?p?=?.002), and 1.0 to 3.5?g/day (ICR II) (adjusted HR, 0.12 [95%CI, 0.02–0.64], p?=?.013) were significantly associated with avoiding a 30% decrease in eGFR, compared to that at no remission.

Conclusions: Attaining lower proteinuria predicts good renal survival in Japanese patients with IMN. This study quantifies the impact of proteinuria reduction in IMN and the clinical relevance of achieving subnephrotic proteinuria in IMN as a valuable prognostic indicator for both the clinician and patient.     

The efficacy of tonsillectomy on clinical remission and relapse in patients with IgA nephropathy: a randomized controlled trial

Background The efficacy of tonsillectomy in immunoglobulin A nephropathy (IgAN) remains controversial. The aim of the study was to conduct a randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgAN. Methods We randomly selected 98 patients with biopsy-proven IgA nephropathy and randomly allocated to receive tonsillectomy combined with drug therapy (Group A) or drug therapy alone (Group B). The participating patients were entered into a 4-year single-center study. Remission and relapse rate were calculated for hematuria and proteinuria using the Kaplan–Meier method. Results No differences were found between the two groups in their baseline clinical and histological characteristics. Patients with tonsillectomy exhibited considerable improvement in the following aspects compared to those patients who did not undergo tonsillectomy: time to reach first remission (3.1 vs. 24.9 months, p?p?p?p?p?=?0.0047) for hematuria and (23.5 vs. 10.5 months, p?=?0.0012) for proteinuria, as well as lower relapse rate for hematuria and proteinuria in Group A. Conclusion Our clinical data demonstrated that tonsillectomy could be beneficial for IgAN patients, particularly by contributing to faster and longer remission, as well as reducing the frequency of possible future relapses.     

The assessment of P-wave dispersion and myocardial repolarization parameters in patients with chronic kidney disease

Objective: The risks of sudden death and cardiac arrhythmia are increased in patients with chronic kidney disease (CKD). Here, we aimed to evaluate the indicators of arrhythmias, such as p-wave dispersion (P-WD), QTc dispersion, Tp-e and Tp-e/QT ratio in patients with CKD stages 3–5 on no renal replacement therapy (RRT).

Material and methods: One-hundred and thirty three patients with CKD stages 3–5 and 32 healthy controls were enrolled into the study. No patients received RRT. QTc dispersion, P-WD and Tp-e interval were measured using electrocardiogram and Tp-e/QT ratio was also calculated.

Results: Mean age rates were found similar in patients and controls (60.8?±?14.2 and 61?±?12.9?y, p?=?.937, respectively). Compared patients with controls, P-WD (45.85?±?12.42 vs. 21.17?±?6.6?msec, p?p?p?p?p?p?=?.001) were found to be different. QTc-max and Tp-e interval were found to be similar in both groups.

Conclusion: P-WD and QTc dispersion, Tp-e interval and Tp-e/QTc ratio were found to be increased in with CKD stages 3–5 on no RRT.     

Effect of oxygen therapy on chest pain in patients with ST elevation myocardial infarction: results from the randomized SOCCER trial

Objective. Oxygen (O₂) have been a cornerstone in the treatment of acute myocardial infarction. Studies have been inconclusive regarding the cardiovascular and analgesic effects of oxygen in these patients. In the SOCCER trial, we compared the effects of oxygen treatment versus room air in patients with ST-elevation myocardial infarction (STEMI). There was no difference in myocardial salvage index or infarct size assessed with cardiac magnetic resonance imaging. In the present subanalysis, we wanted to evaluate the effect of O₂ on chest pain in patients with STEMI. Design. Normoxic patients with first time STEMI were randomized in the ambulance to standard care with 10?l/min O₂ or room air until the end of the percutaneous coronary intervention (PCI). The ambulance personnel noted the patients´ chest pain on a visual analog scale (VAS; 1-10) before randomization and after the transport but before the start of the PCI, and also registered the amount of morphine given. Results. 160 patients were randomized to O₂ (n?=?85) or room air (n?=?75). The O₂ group had a higher median VAS at randomization than the air group (7.0?±?2.3 vs 6.0?±?2.9; p?=?.02) and also received a higher median total dose of morphine (5.0?mg?±?4.4 vs 4.0?mg?±?3.7; p?=?.02). There was no difference between the O₂ and air groups in VAS at the start of the PCI (4.0?±?2.4 vs 3.0?±?2.5; p?=?.05) or in the median VAS decrease from randomization to the start of the PCI (?2.0?±?2.2 vs ?1.0?±?2.9; p?=?.18). Conclusion. Taken together with previously published data, these results do not support a significant analgesic effect of oxygen in patients with STEMI.

European Clinical Trials Database (EudraCT): 2011-001452-11.

ClinicalTrials.gov Identifier: NCT01423929     

Serum galactose-deficient immunoglobulin A1 in recurrent immunoglobulin a nephropathy after kidney transplantation: A meta-analysis

BackgroundImmunoglobulin A nephropathy (IgAN) is a main cause of end stage renal disease (ESRD). Many IgAN patients with ESRD accept kidney allograft for renal replacement. However, disease recurrence occurs after transplantation. Galactose-deficient immunoglobulin A1(Gd-IgA1) has been proved to be a crucial biomarker in the primary IgAN population.MethodsThis meta-analysis aimed to explore the association between serum Gd-IgA1 and IgAN recurrence after renal transplantation and was registered on PROSPERO: CRD42022356952; A literature search was performed and relevant studies were retrieved from the PubMed, Embase and Cochrane library databases from inception to April 27, 2023. The inclusion criteria were: 1) full-text studies; 2) patients with histological diagnosis of IgAN of their native kidneys who underwent kidney transplantation; 3) studies exploring the relationship between serum Gd-IgA1 and IgAN recurrence after kidney transplantation. The exclusion criteria were: 1) reviews, case reports, or non-clinical studies. 2) studies with insufficient original data or incomplete data. 3) studies with duplicated data. Study quality was assessed using Newcastle Ottawa Scale (NOS). Data were pooled using a random-effects model.Results8 full-text studies including 515 patients were identified. The Newcastle-Ottawa Scale (NOS) score ranged from 6 to 8. The standard mean difference (SMD) of the level of Gd-IgA1 was significantly higher in recurrence group than in non-recurrence group (SMD = 0.50，95%CI = 0.15–0.85, p = 0.005). Furthermore, Gd-IgA1 levels were higher in recurrence patients than in non-recurrence in both Europe subgroup (SMD 0.45, 95%CI: 0.08–0.82, p = 0.02) and Asia subgroup (SMD 0.90, 95%CI: 0.10–1.70, p = 0.03). However, pretransplant Gd-IgA1 levels showed no significant difference between recurrence and non-recurrence group (SMD 0.46, 95%CI: 0.06–0.99, p = 0.08) in anther subgroup analysis while posttransplant Gd-IgA1 levels were significantly higher in recurrence population than in non-recurrence (SMD 0.57, 95%CI 0.21 to 0.92, p = 0.002).ConclusionsThis meta-analysis showed that posttransplant serum Gd-IgA1 levels are associated with IgAN recurrence after kidney transplantation; however, pretransplant serum Gd-IgA1 levels are not.     

Changes in the inflammatory markers with advancing stages of diabetic nephropathy and the role of pentraxin-3

Background: Immunological and inflammatory mechanisms have been shown to have role in both the development and progression of diabetic nephropathy (DNP). There is need for more specific markers for inflammation as the ones commonly used are influenced by many factors. Pentraxin-3 (PTX-3) seems to be a potential candidate. We aimed in our study to evaluate the changes of PTX-3 levels in different stages of DNP and its relationship with other inflammatory markers.

Methods: This is a cross sectional study in which patients with DNP at different stages were involved. Patient were divided into three groups according to estimated glomerular filtration rate (eGFR), microalbuminuria and proteinuria levels: Group-1: eGFR >60?mL/min and microalbuminuria, Group-2: eGFR >60?mL/min and macroalbuminuria, Group-3: eGFR <60?mL/min and macroalbuminuria. Besides the routine biochemical parameters, levels of PTX-3, high sensitivity C-reactive protein (hsCRP), interleukin (IL)-1 and tumor necrosis factor (TNF)-α was measured. Groups were compared with each other regarding the study parameters and correlation of PTX-3 with other markers was evaluated.

Results: The mean PTX-3 level in Group-2 (0.94?±?0.26?ng/mL) and -3 (1.35?±?1.55?ng/mL) were higher than in Group-1 (0.81?±?0.25?ng/mL) (p?=?0.009 and p?=?0.012). There was a significant correlation of PTX-3 with proteinuria (r?=?0.266, p?=?0.016), microalbuminuria (r?=?0.304, p?=?0.014) and hypoalbuminemia (r?=?0.197, p?=?0.043). PTX-3 was not correlated with other markers of inflammation (IL-1, TNF-α and hsCRP) and diabetic metabolic parameters (hbA1c, C-peptide, insulin and HOMA-IR). PTX-3, IL-1 and TNF-α levels increased with the advancing stage of DNP while hsCRP level did not change.

Conclusion: PTX-3 that increases similar to other markers of inflammation (IL-1, TNF-α) is a better inflammatory marker than hsCRP. Furthermore, there is a relationship between PTX-3 and proteinuria independent from eGFR.     

Subdermal nitrous oxide delivery increases skin microcirculation and random flap survival in rats

Random skin flaps are essential tools in reconstructive surgery. In this study, we investigated the effect of subdermal nitrous oxide (N₂O) application on random flap survival. In this experimental study, we used 21 female rats in three groups. In the N₂O and air groups, gases were administrated under the proposed dorsal flap areas daily for seven days. Following the treatment period, flaps were raised and inserted back into their place from the dorsal skin. In the control group, the flaps were elevated and inserted back to their place without any pretreatment. Calculation of necrotic flap areas, histological examination and microangiography was performed to evaluate the results 7 days after the flap surgery. The average of necrotic flap area in the N₂O, air and control group was 13.45%, 37.67% and 46.43%, respectively. (N₂O vs air p?=?.044; N₂O vs control p?=?.003). The average number of capillary formations identified in the histological analysis was 7.0?±?1.58, 3.75?±?2.36 and 4.4?±?0.54 in the N₂O, air and control group, respectively. (N₂O vs air p?=?.017; N₂O vs control p?=?.037). The average number of capillary structures identified in the angiography images were 6.3?±?1.52, 1.6?±?1.15 and 1.3?±?0.57 in the N₂O, air and control group, respectively. (N₂O vs air p?=?.04; N₂O vs control p?=?.02). We conclude that subdermal N₂O application increases random flap survival through an increase in the skin microcirculation and could be promising for future clinical applications.     

Clinical characteristics of sepsis-induced acute kidney injury in patients undergoing continuous renal replacement therapy

Objective: The aim of this study was to investigate the clinical characteristics of sepsis-induced acute kidney injury (AKI) in patients undergoing continuous renal replacement therapy (CRRT).

Methods: From 2011 to 2015, we enrolled 340 patients who were treated with CRRT for sepsis at the Presbyterian Medical Center. In all patients, CRRT was performed using the PRISMA platform. We divided these patients into two groups (survivors and non-survivors) according to the 28-day all-cause mortality. We compared clinical characteristics and analyzed the predictors of mortality.

Results: The 28-day all-cause mortality was 62%. Survivors were younger than non-survivors and had higher platelet counts (178?±?101?×?10³/mL vs. 134?±?84?×?10³/mL, p?p?p?p?0.05?mL/kg/h (66% vs. 86%, p?=?.001) in the first day. In a multivariate logistic regression analysis, age, platelet count, RDW score, APACHE II score, serum creatinine level, and a urine output of <0.05?mL/kg/h the first day were prognostic factors for the 28-day all-cause mortality.

Conclusion: Age, platelet count, APACHE II score, RDW score, serum creatinine level, and urine output the first day are useful predictors for the 28-day all-cause mortality in sepsis patients requiring CRRT.     

IgA nephropathy: association of C4d with clinical and histopathological findings and possible role of IgM

Abstract

Background: In patients with IgA nephropathy (IgAN) lectin and alternative pathways of the complement can be activated. Our aim was to analyze the association of glomerular and extraglomerular C4d staining—the representative of lectin pathway—with demographic, clinical and histopathological findings in primary IgAN patients. Design: Seventy-three patients were enrolled and after re-evaluation 37 of them were included in this study. Biopsies were analyzed for staining with anti-C4d primary monoclonal antibody by immunohistochemistry. Patients were classified as positive and negative groups based on their glomerular C4d deposition. Groups were compared for their baseline clinical and histopathological findings. Results: Sixteen (43.2%) of 37 patients were C4d-positive. Glomerular C4d-staining was associated with more severe proteinuria (2906?mg/day vs. 1091?mg/day; p?=?0.002), lower GFR (54.87?mL/min vs. 95?mL/min; p?=?0.023), higher blood pressure (p?=?0.022), more severe endocapillary hypercellularity (p?<?0.001) and more severe tubular atrophy (p?<?0.01). Mesangial IgM deposition was found to be associated with glomerular C4d staining and nephrotic range proteinuria. Conclusions: Glomerular C4d deposition was found to be associated with more unfavorable histopathological and clinical findings at the time of diagnosis. Association of mesangial IgM deposition with the activation of lectin pathway is a novel finding. Mesangial IgM deposition in our patients may reflect the genetic heterology of IgAN between diverse populations. However, since these data are about association, a cause-and-effect about IgM and IgAN cannot be proven solely with these findings.     

Does surgical technique influence the postoperative hemodynamic disturbances and neurological outcomes in carotid endarterectomy?

Introduction: The carotid endarterectomy is already well established in patients with symptomatic or asymptomatic internal carotid artery (ICA) stenosis. The aim of this study was to determine whether there is a difference in postoperative blood pressure changes, stroke rate and postoperative complications following eversion carotid endarterectomy (E-CEA) and conventional carotid endarterectomy (C-CEA).

Methods: From 1 January 2010 to 31 March 2017 consecutive patients admitted to our department with symptomatic or asymptomatic ICA stenosis were included in this retrospective study. During the 7-year period, 175 CEAs were performed in 166 consecutive patients (25 females, 141 males; mean age 70.6?±?14.4 years; range 47 to 92 years).

Results: The mean operative and cross-clamping time were shorter for E-CEA (72?±?14.3?minutes vs. 115?±?17.4?minutes, p?<?.001), (22?±?7.7 vs 34?±?6.3, p?<?.001) respectively. No significant difference was noted between the groups for the occurrence of perioperative stroke (p?=?.501). No significant difference was noted for postoperative blood pressure difference on the 6th hour and the 24th hour after surgery between E-CEA and C-CEA (p?=?.130).

Conclusions: E-CEA was associated with significant reduction in operative time and cross-clamping time however, increases postoperative bleeding. No difference was noted for postoperative stroke and blood pressure distortion between E-CEA and C-CEA.     

A Novel Biomarker for Post-Transplant Recurrent IgA Nephropathy

Background

The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence.

Long-term outcomes of bilateral direct-to-implant breast reconstruction in women at high breast cancer risk

Introduction: Challenges of direct-to-implant breast reconstruction (BR) are to achieve sufficient implant coverage and lower pole projection. We assessed reoperation rates, long-term patient satisfaction and aesthetic outcome after direct-to-implant BR without acellular dermal matrix (ADM) in women with high breast cancer risk.

Methods: Women who underwent bilateral skin or nipple-sparing mastectomy and immediate direct-to-implant BR between 1994 and 2006 completed a survey on reoperations and the Breast-Q Reconstruction questionnaire. Photographs taken during follow-up were rated for long-term aesthetic outcome (scale 1–10) by five plastic surgeons. Outcomes were compared between women who never underwent unanticipated reoperations after immediate BR and women who underwent one or more reoperations, adjusted for potential confounders using multivariable linear regression.

Results: Of 143 women, 70 (49%) were never reoperated and 73 (51%) had undergone reoperations. Median follow-up was 12?years in both groups (range 7–17 and 6–19?years, respectively). Baseline characteristics were comparable except for history of prophylactic oophorectomy with 81% in the no-reoperations group versus 66% in the reoperated group (p?=?.03). Breast-Q scores were 59.7?±?17.3 versus 58.0?±?17.8 (p?=?.67) for ‘satisfaction with breasts’ and 71.1?±?20.3 versus 68.1?±?22.9 (p?=?.47) for ‘satisfaction with outcome’ in the no-reoperation versus reoperation group, respectively. Aesthetic outcome was scored 5.8?±?1.1 in the no-reoperation group versus 5.3?±?1.3 in the reoperation group (p?=?.01).

Conclusions: The single-stage intent did not prevent unanticipated surgical reinterventions in 51% of the patients. Long-term patient satisfaction was reasonable and not affected by reoperations. Aesthetic outcome, however, was only poor to reasonable and scores were significantly lower in the reoperated group.     

Severity of nephrotic IgA nephropathy according to the Oxford classification

Background

IgA nephropathy with nephrotic syndrome (nephrotic IgAN) is a rare form of IgAN. Its prognosis and response to steroid therapy are still controversial because the differential diagnosis between nephrotic IgAN and minimal change nephrotic syndrome with IgA depositions is sometimes confused.

Methods

In this retrospective cohort analysis, we accurately diagnosed 42 cases of nephrotic IgAN (4.4%) from 954 IgAN patients, according to the Oxford classification. We analyzed the clinical and histological data, prognosis, and response to steroid therapy.

Results

In nephrotic IgAN, mean estimated glomerular filtration rate (eGFR) was 51.1?±?24.6?ml/min, proteinuria was 5.71?±?2.56?g/day, and urinary red blood cells were 51.0?±?37.8 high power field. Both active and chronic histological lesions were observed. Cumulative renal survival rate was significantly lower in nephrotic IgAN than in non-nephrotic IgAN (the control group consisted of 47 non-nephrotic IgAN patients diagnosed between 1995 and 1996) (log-rank test: P?Conclusion Nephrotic IgAN is a very severe form of IgAN, with renal dysfunction, massive hematuria, and active and chronic histopathological lesions. Renal outcome is severe; however, steroid therapy can improve prognosis in cases with higher eGFR and lower T-grade, according to the Oxford classification.     

NGAL and NT-proBNP levels in diabetic patients with macroproteinuria

Abstract

Background: In patients with heart failure plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are correlated to urine neutrophil gelatinase-associated lipocalin (NGAL) levels. We prospectively evaluated the relationship among glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), urine and serum NGAL and NT-proBNP levels in 20 type II diabetic patients with macroalbuminuria at 4-month intervals. Results: Compared with 20 age, gender-matched healthy controls, diabetic patients had higher urine and serum NGAL, serum NT-proBNP and lower eGFR. The eGFR of the patients at the baseline, the 4th and the 8th month were 29.6?±?12.0, 27.8?±?13.7 and 22.9?±?10.4?mL/min/1.73?m², respectively. No significant change in urine NGAL levels was detected (p?>?0.05), whereas there were significant increases in NT-proBNP, serum NGAL and urine ACR and significant decrease in eGFR as the study progressed (p?<?0.05). Both the baseline and the 4th month urine ACR were positively correlated to NT-proBNP levels measured at the same periods (r: 0.451; p: 0.046; r: 0.489; p: 0.029 respectively). In all measurements, urine ACR was negatively correlated to serum albumin levels measured at the same periods (r: ?0.792; p: 0.000; r: ?0.716; p: 0.000; r: ?0.531; p: 0.016 respectively). None of eGFR measurements was correlated with NT-proBNP (p?>?0.05). Neither serum NGAL nor urinary NGAL levels are associated with NT-proBNP (p?>?0.05). Conclusion: Our findings show an association between NT-proBNP and proteinuria in type II diabetic patients with macroalbuminuria but not with serum and urine NGAL.     

Quantification of the left atrium applying cardiovascular magnetic resonance in clinical routine

Objectives. In recent years the impact of the left atrium (LA) has become more evident in different cardiovascular pathologies. We aim to provide LA parameters in healthy volunteers for cardiovascular magnetic resonance (CMR) using a fast approach. Design. We analyzed 203 healthy volunteers (mean age 44.6 years (y), range 19y–76y) at 1.5 and 3.0 Tesla (T) using steady-state free precession (SSFP) cine in routine long axis view. Left atrial enddiastolic volume (LA-EDV), endsystolic volume (LA-ESV), stroke volume (LA-SV) and ejection fraction (LA-EF) were quantified and indexed to body-surface-area (BSA). Dependency on age and sex was analyzed. Results. 21 subjects had to be excluded. In the remaining, there was no significant difference between 1.5 T and 3.0 T. Absolut LA-EDV and LA-ESV were larger in men than in women (LA-EDV: male 70?±?19?ml vs. female 61?±?16?ml (p?=?.001); LA-ESV: male 24?±?9?ml vs. female 21?±?8?ml (p?=?.01)). These differences disappeared after indexing to BSA (LA-EDV/BSA: male 34?±?10?ml/m² vs. female 33?±?9?ml/m² (p?=?.65) and LA-ESV/BSA: male 12?±?4?ml/m² vs. female 11?±?4?ml/m² (p?=?.71)). LA-EDV/BSA decreased with older age. Conclusions. Reference values for LA size and function based on a fast approach are provided. LA size decreases with older age. Normalization to body size overcomes sex-dependency. Reports should be related to body size.     

Effects Of Endothelin-1 On Intracellular Tetrahydrobiopterin Levels In Vascular Tissue

Objective: Tetrahydrobiopterin (BH4) is the essential cofactor of endothelial nitric oxide synthase (eNOS) and intracellular levels of BH4 is regulated by oxidative stress. The aim of this paper was to describe the influence of exogenous endothelin-1 on intracellular BH4 and its oxidation products dihydrobiopterin (BH2) and biopterin (B) in a wide range of vascular tissue.

Design: Segments of internal mammary artery (IMA) and human saphenous vein (SV) from 41 patients undergoing elective surgery were incubated in ET-1 (0.1?μM). Aorta and lung from transgenic mice overexpressing ET-1 in the endothelium (ET-TG) were analysed with regards to intracellular biopterin levels. Human umbilical vein endothelial cells (HUVEC) were incubated in ET-1 (0.1?μM) and intracellular biopterin levels were analysed. From 6 healthy women undergoing caesarean section, subcutaneous fat was harvested and the resistance arteries in these biopsies were tested for ET-mediated endothelial dysfunction.

Results: In HUVEC, exogenous ET-1 (0.1?μM) did not significantly change intracellular BH4, 1.54?±?1.7 vs 1.68?±?1.8?pmol/mg protein; p?=?.8. In IMA and SV, exogenous ET-1(0.1?μM) did not change intracellular BH4 n?=?10, p?=?.4. In aorta from wild type vs ET-TG mice there was no significant difference in intracellular BH4 between the groups: 1.3?±?0.49 vs 1.23?±?0.3?pmol/mg protein; p?=?.6. In resistance arteries (n?=?6) BH4 together with DTE (an antioxidant) was not able to prevent ET-mediated endothelial dysfunction.

Conclusion: ET-1 did not significantly alter intracellular tetrahydrobiopterin levels in IMA, SV, HUVEC or aorta from ET-TG mice. These findings are important for future research in ET-1 mediated superoxide production and endothelial dysfunction.     

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study

Objectives: Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort.

Methods: One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed.

Results: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p?r?=??.143, p?=?.047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207?ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (<3.207?ng/ml) and with anti-PTX3 auto-antibodies (4.79 (3.39–8.28) versus 3.95 (1.78–7.0), p?=?.03; 168.84?±?153.63 versus 101.44?±?47.36, p?=?.01; 34.1% (14/41) versus 0% (0/9), p?=?.04; respectively).

Conclusion: Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.     

The prognostic value of platelet-to-lymphocyte ratio on the long-term renal survival in patients with IgA nephropathy

Purpose

Platelet-to-lymphocyte ratio (PLR) was established showing the poor prognosis in several diseases, such as malignancies and cardiovascular diseases. But limited study has been conducted about the prognostic value of PLR on the long-term renal survival of patients with Immunoglobulin A nephropathy (IgAN).

Methods

We performed an observational cohort study enrolling patients with biopsy-proven IgAN recorded from November 2011 to March 2016. The definition of composite endpoint was eGFR decrease by 50%, eGFR?<?15 mL/min/1.73 m², initiation of dialysis, or renal transplantation. Patients were categorized by the magnitude of PLR tertiles into three groups. The Kaplan–Meier curves and multivariate Cox models were performed to determine the association of PLR with the renal survival of IgAN patients.

Results

330 patients with a median age of 34.0 years were followed for a median of 47.4 months, and 27 patients (8.2%) had reached the composite endpoints. There were no differences among the three groups (PLR?<?106, 106?≤?PLR?≤?137, and PLR?>?137) in demographic characteristics, mean arterial pressure (MAP), proteinuria, and estimated glomerular filtration rate (eGFR) at baseline. The Kaplan–Meier curves showed that the PLR?>?137 group was significantly more likely to poor renal outcomes than the other two groups. Using univariate and multivariate cox regression analyses, we found that PLR?>?137 was an independent prognostic factor for poor renal survival in patients with IgAN. Subgroup analysis revealed that the PLR remained the prognostic value for female patients or patients with eGFR less than 60 mL/min/1.73 m².

Conclusions

Our results underscored that baseline PLR was an independent prognostic factor for poor renal survival in patients with IgAN, especially for female patients or those patients with baseline eGFR less than 60 mL/min/1.73 m².

     

Urinary kidney injury molecules in children with febrile seizures

Objective: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time.

Methods: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons.

Results: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p?>?0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9?±?9.8; 6.7?±?4.0, respectively; p?p?p?Conclusion: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.