Association between NLRP3 rs10754558 and CARD8 rs2043211 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 < 0.001) between NLRP3 and CARD8 variants and cases. Our results suggest that the NLRP3 rs10754558 and CARD8 rs2043211 variants could be associated with a susceptibility to CKD.

Rapamycin promotes autophagy cell death of Kaposi's sarcoma cells through P75NTR activation.

The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi's Sarcoma (KS), through several biological interactions. In this in vivo and in vitro study, we explored whether the activation of the autophagic pathway through the low-affinity receptor for nerve growth factor, p75NTR , may have a pivotal role in the anti-cancer effect exerted by Rapamycin in S. Our Kimmunohistochemistry results revealed a significant hyper-activation of the autophagic pathway in KS lesions. In vitro experiments on KS cell lines showed that Rapamycin exposure reduced cell viability by increasing the autophagic process, in the absence of apoptosis, through the transcriptional activation of p75NTR via EGR1. Interestingly, p75NTR gene silencing prevented the increase of the autophagic process and the reduction of cell viability. Moreover, p75NTR activation promoted the upregulation of phosphatase and tensin homolog (PTEN), a tumour suppressor that modulates the PI3K/Akt/mTOR pathway. In conclusion, our in vitro data demonstrated, for the first time, that in Kaposi's sarcoma, autophagy triggered by Rapamycin through p75NTR represented a major mechanism by which mTOR inhibitors may induce tumour regression. Additionally, it suggested that p75NTR protein analysis could be proposed as a new potential biomarker to predict response to Rapamycin in kidney transplant recipients affected by Kaposi's sarcoma.

An Olive Leaf Extract Rich in Polyphenols Promotes Apoptosis in Cervical Cancer Cells by Upregulating p21Cip/WAF1 Gene Expression.

Most of the common drugs used to treat the cervical cancer, which main etiological factor is the HPV infection, cause side effects and intrinsic/acquired resistance to chemotherapy. In this study we investigated whether an olive leaf extract (OLE), rich in polyphenols, was able to exert anti-tumor effects in human cervical cancer cells (HeLa). MTT assay results showed a reduction of HeLa cells viability OLE-induced, concomitantly with a gene and protein down-regulation of Cyclin-D1 and an up-regulation of p21, triggering intrinsic apoptosis. OLE reduced NFkB nuclear translocation, which constitutive activation, stimulated by HPV-oncoproteins, promotes cancer progression and functional studies revealed that OLE activated p21Cip/WAF1 in a transcriptional-dependent-manner, by reducing the nuclear recruitment of NFkB on its responsive elements. Furthermore, OLE treatment counteracted epithelial-to-mesenchymal-transition and inhibited anchorage-dependent and -independent cell growth EGF-induced. Finally, MTT assay results revealed that OLE plus Cisplatin strengthened the reduction of cells viability Cisplatin-induced, as OLE inhibited NFkB, AkT and MAPK pathways, all involved in Cisplatin chemoresistance. In conclusion, we demonstrated that in HeLa cells OLE exerts pro-apoptotic effects, elucidating the molecular mechanism and that OLE could mitigate Cisplatin chemoresistance. Further studies are needed to explore the potential coadiuvant use of OLE for cervical cancer treatment.

NFKB1 promoter polymorphism: A new predictive marker of cytomegalovirus infection after kidney transplantation.

INTRODUCTION: Cytomegalovirus (CMV) infection represents a common cause of morbidity and mortality in kidney transplant recipients (KTR). The NF-kB signaling pathway is highly involved in the pathogenesis of CMV infection. The -94ins/delATTG functional polymorphism in the promoter of NFKB1 has been associated with low intracellular levels of the protein and high incidence of inflammatory and autoimmune disease. In this study, we evaluated the association of this NFKB1 polymorphism with the risk of CMV infection. METHODS: CMV infection was defined as virus isolation or detection of viral antigens or nucleic acid in any body fluid or tissue specimen. Using Cox regression and survival analysis, we analyzed the association between the polymorphism and CMV infection as well as recurrence in the first 12 months after transplantation. RESULTS: We analyzed the -94ins/delATTG NFKB1 polymorphism of 189 KTRs. The 65% of CMV infections occurred in ins/ins group. Survival free from CMV infection was 54.7% for ins/ins group and 79.4% for deletion carriers one year after transplantation (P < 0.0001). At multivariate regression, deletion carriers showed a lower risk of CMV infection and recurrence with respect to ins/ins KTRs (HR = 0.224 P = 0.0002; HR = 0.307, P = 0.012, respectively). CONCLUSIONS: In conclusion, pretransplantation screening for NFKB1 -94ins/delATTG polymorphism may predict CMV infection and improve the management of patients at higher risk of infection in the post-transplant period.

Efficacy of eculizumab in severe ADAMTS13-deficient thrombotic thrombocytopenic purpura (TTP) refractory to standard therapies.

Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic hemolytic anemia (MAHA) defined by mechanical hemolytic anemia, severe thrombocytopenia, and systemic visceral ischemia due to systemic platelet-rich microthrombi. Forty percent of patients with autoimmune TTP experience one or multiple relapses. Patients with refractory TTP are currently managed by corticosteroids, twice-daily PEX, and the anti-CD20 monoclonal antibody rituximab. Herein, we report two cases of severe TTP, refractory to those standard agents. On the basis of the fact that in cases of severe TTP the classical complement pathway is activated, and that the alternative pathway is also involved, both patients underwent eculizumab (anti-C5 monoclonal antibody) therapy. We observed prompt hematological and organ system responses to the eculizumab and the recovery of plasma ADAMTS-13 activity in both cases. Moreover, the fact that both patients discontinued eculizumab, maintaining the response, emphasizes the possibility of its usefulness for limited treatment periods. In conclusion, the diagnostic and therapeutic algorithm in TTP appears complicated by increasing evidence of complement involvement and the eculizumab seems to be a potential agent for refractory patients.

Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort.

BACKGROUND: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. METHODS: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. RESULTS: In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ≥0.4 g/day/1.73 m2 and an eGFR of <90 ml/min/1.73 m2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m2) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. CONCLUSION: This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

Nerve growth factor exposure promotes tubular epithelial-mesenchymal transition via TGF-ß1 signaling activation.

Clinical studies showed that renal expression and serum levels of nerve growth factor (NGF) are increased in renal diseases characterized by progressive fibrosis, a pathologic process in which TGF-ß1 mediates most of the key events leading to tubular epithelial-mesenchymal transition (EMT). However, the pathogenic role of high NGF levels has not yet been elucidated. In this study, we found that in tubular renal cells, HK-2, NGF transcriptionally up-regulated TGF-ß1 expression and secretion and enhanced cell motility by activating EMT markers via its receptors, TrkA and p75(NTR). Interestingly, we observed that TGF-ß1-SMAD pathway activation and the up-regulation of EMT markers NGF-induced were both prevented when knockdown of TGF-ß1 gene occurred and that the pretreatment with an antibody anti-NGF reversed the nuclear translocation of pSMAD3/SMAD4 complex. Collectively, our results demonstrated that NGF promotes renal fibrosis via TGF-ß1-signaling activation, suggesting that in kidney diseases high NGF serum levels could contribute to worsen renal fibrosis.

The Missense Variant in the Signal Peptide of α-GLA Gene, c.13 A/G, Promotes Endoplasmic Reticular Stress and the Related Pathway's Activation.

Anderson-Fabry disease (AFD) is an X-linked multisystemic disorder with a heterogeneous phenotype, resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and leading to globotriaosylceramide systemic accumulation. Lysosomal storage is not the unique player in organ failure and different mechanisms could drive tissue damage, including endoplasmic reticulum (ER) stress and its related signaling pathway's activation. We identified a new missense variant in the signal peptide of α-GLA gene, c.13 A/G, in a 55-year-old woman affected by chronic kidney disease, acroparesthesia, hypohidrosis, and deafness and exhibiting normal values of lysoGb3 and αGLA activity. The functional study of the new variant performed by its overexpression in HEK293T cells showed an increased protein expression of a key ER stress marker, GRP78, the pro-apoptotic BAX, the negative regulator of cell cycle p21, the pro-inflammatory cytokine, IL1ß, together with pNFkB, and the pro-fibrotic marker, N-cadherin. Transmission electron microscopy showed signs of ER injury and intra-lysosomal inclusions. The proband's PBMC exhibited higher expression of TGFß 1 and pNFkB compared to control. Our findings suggest that the new variant, although it did not affect enzymatic activity, could cause cellular damage by affecting ER homeostasis and promoting apoptosis, inflammation, and fibrosis. Further studies are needed to demonstrate the variant's contribution to cellular and tissue damage.

Anaemia management in non-dialysis chronic kidney disease (CKD) patients: a multicentre prospective study in renal clinics.

BACKGROUND: Knowledge on anaemia management in non-dialysis chronic kidney disease (ND-CKD) patients regularly followed in renal clinics is scarce although being essential to identifying areas of therapeutic improvement. METHODS: We prospectively evaluated anaemia management in two visits, performed 6 months apart, in 755 prevalent ND-CKD stage 3b-5 patients followed in 19 nephrology clinics from ≥6 months. Anaemia was defined as severe (Hb <11 g/dL) or mild (Hb: 11-13.5 in males and 11-12 g/dL in females); iron deficiency (ID) was defined as transferrin saturation (TSAT) <20% and/or ferritin <100 ng/mL. Primary endpoint was the change of anaemia and ID prevalence between baseline and 6-month visit. Secondary endpoint was the prevalence of clinical inertia to either ESA or iron supplementation, that is, the lack of ESA or iron prescription despite Hb <11 g/dL or ID. RESULTS: Age was 69 ± 13 years and GFR 27.5 ± 10.0 mL/min/1.73 m(2); male gender, diabetes and prior cardiovascular disease were 57.2, 30.1 and 30.1%, respectively. Prevalence of severe and mild anaemia was 18.0 and 44.0% at baseline and remained unchanged at Month 6 (19.3 and 43.2%). ID was prevalent at both visits (60.1 and 60.9%). Clinical inertia to ESA was similar at baseline and at Month 6 (39.6 and 34.2%, respectively, P = 0.487) and it was less frequent than clinical inertia to iron therapy (75.7 and 72.0%, respectively). CONCLUSIONS: This study shows that anaemia prevalence is unexpectedly high in the setting of tertiary nephrology care. This was due to a persistent clinical inertia in the anaemia management, remarkable for iron supplementation and less critical, but still significant, for ESA treatment.

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 < 0.0001 and r = -0.1882, p < 0.0001, respectively). The same direct correlation was found in adolescents according to their sex. Our findings highlight the potential of the Veggie Meter® as a feasible and promising tool for evaluating adherence to the MD and, ultimately, to promote healthy eating habits among adolescents.

[Intestinal and renal transport mechanisms of phosphate]. / Meccanismi di trasporto del fosfato nell'intestino e nel rene.

Since phosphorus plays a critical role in diverse biological processes, regulation of the phosphorus balance and homeostasis are critical to the well-being of the organism. Recent findings point to the presence of a phosphate-sensing mechanism in the various organs and the presence of novel intestinal effectors that alter the renal phosphate excretion after the ingestion of a phosphate-containing meal. Recent studies have provided strong evidence that the sodium-phosphate cotransporter NaPi-IIb is responsible for sodium-dependent phosphate absorption by the small intestine, and this protein might link changes in dietary phosphate to altered renal phosphate excretion in order to maintain the phosphate balance. It has been established that different regions of the small intestine respond differently to acute or chronic changes in dietary phosphate load and that phosphatonins inhibit both renal and intestinal phosphate transport.

Proinflammatory profile of visceral adipose tissue and oxidative stress in severe obese patients carrying the variant rs4612666 C of NLRP3 gene.

BACKGROUND: The activation of NLRP3 inflammasome machinery has a central role in obesity-induced inflammation. Genetic studies well support the involvement of functional variants of NLRP3 and its negative regulator, CARD8, in the pathogenesis of complex diseases with an inflammatory background. We have investigated the influence of NLRP3 (rs4612666; rs10754558) and CARD8 (rs204321) genetic variants in both the inflammatory status of visceral adipose tissue (VAT) from patients with severe obesity and in the systemic oxidative stress before and after sleeve-gastrectomy (SLG). METHODS: Twenty-three consecutive severe obese patients candidate to SLG were enrolled in the study. Visceral adipose tissue (VAT) biopsies, obtained during SLG, were used to evaluate the expression of NLRP3, IL-1ß, IL-6, and MCP-1 by real-time RT-PCR. DNA was extracted from peripheral blood lymphocytes and genotyped by RFLP analysis. Before and 3 months after SLG, all patients underwent the assessment of oxidative stress, biochemical parameters, and body composition as measured by bioelectrical impedance analysis (BIA). RESULTS: Increased expression of NLRP3, IL-6, IL-1ß, and MCP-1 mRNA was observed in VAT of rs4612666 C variant carriers, in which higher oxidative stress was also detected as compared to non-carrier individuals. In all patients, oxidative stress, biochemical and BIA parameters improved after SLG, regardless of genotype. No significant correlations were found with the other genetic variants. CONCLUSIONS: Our results suggest that the NLRP3 rs4612666 C variant may promote a worse pro-inflammatory milieu and higher oxidative stress, thus leading patients to a more severe obesity phenotype. A larger study is needed to confirm this assumption and to investigate the impact of the NLRP3 rs4612666 C variant on severe obesity.

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.

Impact of body mass index on graft loss in normal and overweight patients: retrospective analysis of 206 renal transplants.

BACKGROUND: Excess body mass is increasingly prevalent in transplant recipients. Currently, most investigators consider body mass index (BMI) a categorical variable, which assumes that all risk factors and transplant outcomes will be similar in all patients within the same category. We investigated the effect of categorical and continuous BMI increments on renal transplant outcome in normal weight (NW: BMI 18.5-24.9) and overweight (OW: BMI 25-30) patients. METHODS: We retrospectively studied 206 patients. The mean BMI of our population was 24.3 ± 2.83 kg/m(2) . Patients of each group were similar regarding age, gender, time on dialysis, donor type, cold ischemia time, and number of HLA mismatches. The independent association of BMI with survival was determined using Cox multivariate regression. RESULTS: OW patients showed a higher prevalence of co-morbidities. In patients with graft loss, there was a higher incidence of delayed graft function, chronic allograft nephropathy, acute rejection, and hypertension. Graft survival was significantly lower in OW patients compared to NW patients upon Kaplan-Meier analysis (p = 0.008). In a multivariate Cox regression analysis, the initial BMI, evaluated as a continuous variable, remained an independent predictor of graft loss (hazard ratio 1.21, 95% CI 1.04-1.47). However, with patient stratification into World Health Organization BMI category and, further, into quartiles of initial BMI, no significant correlation between BMI category and graft loss was found. CONCLUSION: We suggest that increasing BMI value, although without categorical variation, may represent an independent risk factor for graft loss. Our retrospective analysis of a small sample population will require further studies to confirm these data.

[Acute renal failure in the course of Hashimoto's thyroiditis]. / Insufficienza renale acuta in corso di tiroidite di Hashimoto.

Hashimoto's thyroiditis is the commonest form of autoimmune thyroiditis in the world. It occurs most frequently in women (female/male ratio, 6:1) in the age group between 30 and 60 years. Here we report the case of a 38-year-old Caucasian man who presented with a few days' history of upper limb paresthesias, widespread joint and muscle pain, and headaches. Laboratory findings showed increased CPK, myoglobin and plasma creatinine levels with acute renal failure. Low free T3 and T4 values associated with a high TSH value, the presence of antithyroid globulin and peroxidase autoantibodies pointed to a diagnosis of hypothyroidism with Hashimoto's thyroiditis. Treatment with levothyroxine was initiated and within 2 months normalization of renal function, myoglobin, CPK and thyroid hormone levels was observed.

Acute Kidney Ischemic Injury in a Rat Model Treated by Human Omental Mesenchymal Stem Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) may provide a novel clinical approach for acute kidney injury (AKI), which represents a severe health care condition. The human omentum is an important source of MSCs. We investigated the effects of human omental mesenchymal stem cells (HO-MSCs) after induction of ischemic AKI in a rat model. METHODS: The ischemic-reperfusion injury (IRI) was induced at reperfusion following a 45-minute clamping of renal vessels. Twenty animals were used in this study. Each rat was randomly assigned to 1 of 2 groups: G1 (control, n = 10; IRI infusion of phosphate buffer solution) or G2 (HO-MSCs, n = 10; IRI infusion of HO-MSCs). The infusions were performed in the parenchyma at reperfusion. Renal function at 1, 3, 5, and 7 days was assessed. At sacrifice, histologic samples were analyzed by light, and renal injury was graded. RESULTS: HO-MSCs induced an accelerated renal exocrine functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys as compared with control groups (P < .05). The renal damage degree was significantly less in the animals of the HO-MSC group (P < .0001). CONCLUSIONS: These results suggest that HO-MSCs could be useful in the treatment of AKI in a rat model with possible potential implication in clinical setting.

Nerve growth factor and its monocyte receptors are affected in kidney disease.

Nerve growth factor (NGF) plays a critical role in both physiological and pathological conditions. Their biological effects are mediated by two receptors (NGF-R): TrkA and p75. We previously reported NGF and NGF-R overexpression in various renal disorders. The aim of the study was to determinate NGF levels and NGF-R expression in peripheral blood mononuclear cells from subjects affected by glomerulonephritis (GN) and by end-stage renal disease before and after hemodialysis (HD). We enrolled 48 patients with biopsy-proven diagnosis of GN and 16 patients undergoing chronic HD. 25 subjects were enrolled as controls (C). Quantification of NGF in the serum samples was performed using NGF immunoassay. We demonstrated, for the first time, an increased NGF concentration in GN and HD patients compared to C. HD is able to restore serum NGF concentration. In GN, TrkA is overexpressed, whereas p75 did not show any difference versus C. By contrast in HD, TrkA expression is associated with increased p75 levels. In conclusion, NGF can act as protective factor against cytotoxic injuries. p75 plays a role in both survival and death of cells, depending on absence of ligand, cytoplasmic/ligand interaction and interaction with TrkA. The present findings suggest that cell survival during cellular damage is dependent on co-expression of TrkA and p75 and independent of NGF concentration. Further studies are required to confirm these observations.

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.

[Identification of a new mutation of the NPHP1 gene].

Kidney cystic diseases are inherited disorders causing chronic renal failure. According to the genetic defect they are classified as diseases of the primary ciliary complex and uromodulin-associated diseases. Mutations in genes coding for ciliary proteins are the basis of a broad category of genetic diseases, called ciliopathies. To date, three important ciliopathies are known: the autosomal dominant form and the recessive shape of the polycystic kidney and the nephronophthisis (NPHP). Juvenile Nephronophthisis (NPHP) is a progressive renal tubulo-interstitial disorder with a form of autosomal recessive inheritance that progresses inexorably towards terminal renal failure. Three different forms have been distinguished: juvenile (NPH1), infantile (NPH2) and adolescent (NPH3). Juvenile Nephronophthisis or nephronophthisis type 1 (NPH1), is the most frequent form. In most patients with a suspected diagnosis of NPHP, based primarily on clinical and radiological data, the deletion in homozygous NPHP1 is present in 20-40% of cases. Heterozygous deletions are found in 6% of patients, with concomitant mutation of the NPHP1 gene on the second allele. In this study we subjected to genetic screening 6 patients with suspected NPHP causing chronic renal failure, belonging to 6 families. The genetic screening identified in 2/6 patients a deletion of exons 5-7-20 and in 4/6 patients an heterozygous deletion of exon 20 and an heterozygous deletion on exon 17 not yet described in literature. Our results suggest that genetic screening should be included in the diagnostic procedure of patients with suspected nephronophthisis and that it may be used alternatively to renal biopsy.