Identification of a New Complement Factor H Mutation in a Patient With Pregnancy-Related Acute Kidney Injury

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Acute Renal Failure in Sarcoidosis: A Review of the Literature

We report two cases of acute kidney failure (ARF) as the initial manifestation of sarcoidosis. Two patients were sent from their primary care physicians with hypercalcemia and progressive increase of serum creatinine. The renal biopsy revealed granulomatous interstitial nephritis (GIN). Both patients were started on Methylprednisolone pulse therapy, followed by administration of oral prednisolone and by a slow taper thereafter to a maintenance dose. The renal function has improved immediately in response to this therapy. Our cases demostrates thet GIN due to sarcoidosis, although a rare entity, can cause severe ARF and progressive ESRD. With early detection and appropriate therapy, the majority of patients will maintain adequate renal function. Therefore the diagnosis of renal sarcoidosis must be done quickly to prevent renal.</p

Association between Skin Carotenoid Score Measured with Veggie Meter^® and Adherence to the Mediterranean Diet among Adolescents from Southern Italy

The Veggie Meter® (Longevity Link Corporation, Salt Lake City, UT, USA), is a new portable device for the non-invasive and rapid detection of skin carotenoid content, which represents an acceptable biomarker for the evaluation of fruit and vegetable (FV) intake. FVs are important components of a healthy diet, including the Mediterranean Diet (MD), which is a plant-based dietary pattern. Here, we evaluated the adherence to the MD via the administration of two online food questionnaires, and we measured the skin carotenoid content using the Veggie Meter® in a cohort of 498 healthy adolescents (233 males and 265 females) from Southern Italy. Using KIDMED and the MD Pyramid tests to assess the adherence to the MD, we found an average adherence (5.43 ± 2.57 and 7.20 ± 1.93, respectively) to the MD in our sample population. Moreover, we observed that the skin carotenoid score was 364.75 ± 98.29, which was within the normal range and inversely related to the BMI (r = −0.1461, p = 0.0011). Similar results were observed when the population was categorized by sex. Interestingly, we demonstrated, for the first time, a positive correlation between the carotenoid score and the adherence to the MD assessed using both the KIDMED and MD Pyramid tests in the total population (r = −0.2926, p p ® as a feasible and promising tool for evaluating adherence to the MD and, ultimately, to promote healthy eating habits among adolescents

Oxidative Balance and Inflammation in Hemodialysis Patients: Biomarkers of Cardiovascular Risk?

During chronic kidney disease, the progressive deterioration of renal function induces several biological/clinical dysfunctions, including enhancement of synthesis of inflammation/oxidative stress mediators. Impaired renal function is an independent cardiovascular risk factor; indeed, cardiovascular complications dominate the landscape of both chronic kidney disease and end-stage renal disease. The aim of this study is to explore the correlation between the global oxidative balance in hemodialysis patients and both inflammatory markers and cardiovascular events. Using photometric tests, this study explored plasmatic oxidative balance in 97 hemodialysis patients compared to a healthy population. In the hemodialysis patients, we showed that oxidative stress values were significantly lower than in controls while effectiveness in the antioxidant barrier was significantly increased in the hemodialysis group. Furthermore, we highlighted a strong correlation between oxidative index and blood levels of C-reactive protein. When patients were divided into two groups based on previous cardiovascular events, we found that subjects with previous cardiovascular events had higher values of both oxidative stress and antioxidant barrier than patients without cardiovascular events. Our results indicated that in hemodialysis patients, the clinical and prognostic significance of oxidative status is very different from general population. As cardiovascular complications represent a strong negative factor for survival of hemodialysis patients, the research of new cardiovascular risk biomarkers in these patients takes on particular importance in order to translate them into clinical practice/primary care

Association between <i>NLRP3 rs10754558</i> and <i>CARD8 rs2043211</i> Variants and Susceptibility to Chronic Kidney Disease

Nod-like receptor protein 3 (NLRP3) is a multi-protein complex belonging to the innate immune system, whose activation by danger stimuli promotes inflammatory cell death. Evidence supports the crucial role of NLRP3 inflammasome activation in the transition of acute kidney injury to Chronic Kidney Disease (CKD), by promoting both inflammation and fibrotic processes. Variants of NLRP3 pathway-related genes, such as NLRP3 itself and CARD8, have been associated with susceptibility to different autoimmune and inflammatory diseases. In this study, we investigated for the first time the association of functional variants of NLRP3 pathway-related genes (NLRP3-rs10754558, CARD8-rs2043211), with a susceptibility to CKD. A cohort of kidney transplant recipients, dialysis and CKD stage 3–5 patients (303 cases) and a cohort of elderly controls (85 subjects) were genotyped for the variants of interest and compared by using logistic regression analyses. Our analysis showed a significantly higher G allele frequency of the NLRP3 variant (67.3%) and T allele of the CARD8 variant (70.8%) among cases, compared with the control sample (35.9 and 31.2%, respectively). Logistic regressions showed significant associations (p NLRP3 rs10754558 and CARD8 rs2043211 variants could be associated with a susceptibility to CKD

Overexpression of p75NTR in Human Seminoma: A New Biomarker?

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs

Exposure to Nerve Growth Factor Worsens Nephrotoxic Effect Induced by Cyclosporine A in HK-2 Cells

<div><p>Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkA^NTR and p75^NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 ^NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75^NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A.</p> </div

CSA up-regulates NGF protein levels via NFATc1.

<p>(A) WB of TrKA^NTR (Antibody dilution 1:300), p75^NTR (1:300) and NGF (1:300) basal protein expression in HK-2 cells. β-Actin (1:10000) was used as loading control. (B) HK-2 cells were untreated (c) or treated for 48h with CsA 10nM-100nM-1μM-4μM-8μM before lysis. Equal amounts of total cellular extract were analyzed for NGF levels by western blotting. β-Actin was used as loading control. Bars represent the means ± SD of 3 separate experiments between NGF/β-Actin levels in which band intensities were evaluated as density arbitrary units and expressed as percentages of the control (100%). *p<0.05 vs c. (C) HK-2 cells were treated with CsA 10nM for 3h. Nuclear and cytosolic fractions were analyzed by immunoblotting using anti-NFATc1 Ab (1:100). β-Actin and Lamin B (1:10000) were used respectively as cytosolic and nuclear loading controls. Immunoblots show a single representative of 3 separate experiments. The upper panels represent the means ± SD of 3 separate experiments between NFATc1/β-Actin and NFATc1/Lamin B levels in which band intensities were evaluated as optical density arbitrary units and expressed as percentages of the control which was assumed to be 100%. *p<0.05 vs c. (D) WB of NFATc1 and NGF in total extracts from HK-2 cells treated with CsA 10nM, PMA 100nM+Io 2.5μM and CsA+PMA+Io β-Actin was used as loading control. The upper panels represent the means ± SD of 3 separate experiments between NFATc1/β-Actin and NGF/β-Actin levels in which band intensities were evaluated in terms of optical density arbitrary units and expressed as percentages of the control (100%). *p<0.05 vs c; **p<0.05 vs CsA-treated cells. All immunoblots show a single representative of 3 separate experiments. Secondary antibodies dilutions used are: goat anti-mouse (1:2000) or anti-rabbit (1:7000) or donkey anti-goat (1:3000) IgG. </p