Indole-3-acetic acid correlates with monocyte-to-high-density lipoprotein (HDL) ratio (MHR) in chronic kidney disease patients.

PURPOSE: Indole-3-acetic acid is a protein-bound indolic uremic toxin deriving from tryptophan metabolism. Increased levels are associated with higher thrombotic risk and both cardiovascular and all-cause mortality. An emerging biomarker of cardiovascular disease is the monocyte-to-high-density lipoprotein ratio (MHR). The main purpose of this study was to investigate the association of indole-3-acetic acid with MHR and other markers of cardiovascular risk in patients with chronic kidney disease (CKD). METHODS: We enrolled 61 non-dialysis CKD patients and 6 dialysis patients. Indole-3-acetic acid levels were measured with ELISA technique. RESULTS: In the whole cohort of 67 patients, indole-3-acetic acid was directly related to Ca × P (ρ = 0.256; P = 0.0365) and MHR (ρ = 0.321; P = 0.0082). In the 40 patients with previous cardiovascular events, indole-3-acetic acid correlated with uric acid (r = 0.3952; P = 0.0116) and MHR (ρ = 0.380; P = 0.0157). MHR was related with fibrinogen (ρ = 0.426; P = 0.0010), arterial hypertension (ρ = 0.274; P = 0.0251), C-reactive protein (ρ = 0.332; P = 0.0061), gender (ρ = - 0.375; P = 0.0017; 0 = male, 1 = female), and CKD stage (ρ = 0.260; P = 0.0337). A multiple regression analysis suggested that indole-3-acetic acid might be an independent predictor of MHR. CONCLUSION: This study shows a significant association between indole-3-acetic acid and MHR. Prospective studies are required to evaluate if decreasing indole-3-acetic acid concentrations may reduce MHR levels and cardiovascular events and improve clinical outcomes.

Renal involvement in sarcoidosis: histological patterns and prognosis, an Italian survey.

BACKGROUND: Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI). METHODS: This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU. RESULTS: Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15-300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints. CONCLUSIONS: sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI.

Maternal peripheral blood CD34+ cells for prediction of fetal kidney malformations: results from a case-control analysis.

PURPOSE: To evaluate the relation between CD34+ cells count in maternal blood and potential development of fetal congenital renal abnormalities. MATERIALS AND METHODS: We enrolled 16 women that gave birth to newborns carrying congenital renal malformations over a 3-year period and 48 women with uncomplicated pregnancies (controls) in a 1:3 ratio (three controls per case). RESULTS: CD34+ cells in the maternal peripheral blood were significantly lower in the group of women who gave birth to newborns carrying congenital renal malformations compared to the controls (p < .0001). CONCLUSIONS: CD34+ cells in maternal blood could be validated as a potential marker to predict the development of possible kidney malformations.

RAS inhibition modulates kynurenine levels in a CKD population with and without type 2 diabetes mellitus.

Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus, mainly through the inflammation-induced activity of indoleamine 2,3-dioxygenase (IDO), and few studies have investigated its potential link with proteinuria. Renin-angiotensin system inhibitors (RASis) are recommended in these patients to decrease proteinuria, slow CKD progression and reduce cardiovascular risk, but whether these drugs influence kynurenine levels in humans is unknown. We evaluated serum tryptophan and kynurenine in patients suffering from CKD with or without type 2 diabetes mellitus, their correlations with markers of reduced kidney function, and their relationship with RAS-inhibiting therapy. Of 72 adult patients enrolled, 55 were receiving RASis, whereas 17 were not. Tryptophan was assessed by HPLC (high-performance liquid chromatography); kynurenine was measured using an enzyme-linked immunosorbent assay kit; IDO activity (%) was calculated with the formula (kynurenine/tryptophan) × 100. Kynurenine levels were significantly lower in the group under RASis compared to the untreated group (1.56 ± 0.79 vs 2.16 ± 1.51 µmol/l; P = 0.0378). In patients not receiving RASis, kynurenine was inversely related to estimated glomerular filtration rate (eGFR) (r = - 0.4862; P = 0.0478) and directly related to both proteinuria (ρ = 0.493; P = 0.0444) and albuminuria (ρ = 0.542; P = 0.0247). IDO activity was higher in patients with history of cardiovascular disease compared to patients with no such history, and it negatively correlated with eGFR (ρ = - 0.554; P = 0.0210) in the same group. These findings may contribute to explain the well-known beneficial effects of RAS inhibition in CKD population, especially considering that kynurenine is emerging as a potential new biomarker of CKD.

Management of dyslipidaemia in patients with chronic kidney disease: a position paper endorsed by the Italian Society of Nephrology.

Chronic kidney disease (CKD) represents a major public health issue worldwide and entails a high burden of cardiovascular events and mortality. Dyslipidaemia is common in patients with CKD and it is characterized by a highly atherogenic profile with relatively low levels of HDL-cholesterol and high levels of triglyceride and oxidized LDL-cholesterol. Overall, current literature indicates that lowering LDL-cholesterol is beneficial for preventing major atherosclerotic events in patients with CKD and in kidney transplant recipients while the evidence is less clear in patients on dialysis. Lipid lowering treatment is recommended in all patients with stage 3 CKD or worse, independently of baseline LDL-cholesterol levels. Statin and ezetimibe are the cornerstones in the management of dyslipidaemia in patients with CKD, however alternative and emerging lipid-lowering therapies may acquire a central role in near future. This position paper endorsed by the Italian Society of Nephrology aims at providing useful information on the topic of dyslipidaemia in CKD and at assisting decision making in the management of these patients.

Role of Vitamin D Status in Diabetic Patients with Renal Disease.

Diabetes mellitus (DM) poses a major public health problem worldwide, with ever-increasing incidence and prevalence in recent years. The Institute for Alternative Futures (IAF) expects that the total number of people with type 1 and type 2 DM in the United States will increase by 54%, from 19,629,000 to 54,913,000 people, between 2015 and 2030. Diabetic Nephropathy (DN) affects about one-third of patients with DM and currently ranks as the first cause of end-stage kidney disease in the Western world. The complexity of interactions of Vitamin D is directly related with progressive long-term changes implicated in the worsening of renal function. These changes result in a dysregulation of the vitamin D-dependent pathways. Various studies demonstrated a pivotal role of Vitamin D supplementation in regression of albuminuria and glomerulosclerosis, contrasting the increase of glomerular basement membrane thickening and podocyte effacement, with better renal and cardiovascular outcomes. The homeostasis and regulation of the nephron's function are absolutely dependent from the cross-talk between endothelium and podocytes. Even if growing evidence proves that vitamin D may have antiproteinuric, anti-inflammatory and renoprotective effects in patients with DN, it is still worth investigating these aspects with both more in vitro studies and randomized controlled trials in larger patient series and with adequate follow-up to confirm the effects of long-term vitamin D analogue supplementation in DN and to evaluate the effectiveness of this therapy and the appropriate dosage.

Mitochondrial Disease (MELAS Syndrome) Discovered at the Start of Pregnancy in a Patient with Advanced CKD: A Clinical and Ethical Challenge.

Pregnancy is a challenge in the life of a woman with chronic kidney disease (CKD), but also represents an occasion for physicians to make or reconsider diagnosis of kidney disease. Counselling is particularly challenging in cases in which a genetic disease with a heterogeneous and unpredictable phenotype is discovered in pregnancy. The case reported regards a young woman with Stage-4 CKD, in which "Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes" (MELAS syndrome), was diagnosed during an unplanned pregnancy. A 31-year-old Caucasian woman, being followed for Stage-4 CKD, sought her nephrologist's advice at the start of an unplanned pregnancy. Her most recent data included serum creatinine 2⁻2.2 mg/dL, Blood urea nitrogen (BUN) 50 mg/dL, creatinine clearance 20⁻25 mL/min, proteinuria at about 2 g/day, and mild hypertension which was well controlled by angiotensin-converting enzyme inhibitors (ACEi); her body mass index (BMI) was 21 kg/m² (height 152 cm, weight 47.5 kg). Her medical history was characterized by non-insulin-dependent diabetes mellitus (at the age of 25), Hashimoto's thyroiditis, and focal segmental glomerulosclerosis. The patient's mother was diabetic and had mild CKD. Mild hearing impairment and cardiac hypertrophy were also detected, thus leading to suspect a mitochondrial disease (i.e., MELAS syndrome), subsequently confirmed by genetic analysis. The presence of advanced CKD, hypertension, and proteinuria is associated with a high, but difficult to quantify, risk of preterm delivery and progression of kidney damage in the mother; MELAS syndrome is per se associated with an increased risk of preeclampsia. Preterm delivery, associated with neurological impairment and low nephron number can worsen the prognosis of MELAS in an unpredictable way. This case underlines the importance of pregnancy as an occasion to detect CKD and reconsider diagnosis. It also suggests that mitochondrial disorders should be considered in the differential diagnosis of kidney impairment in patients who display an array of other signs and symptoms, mainly type-2 diabetes, kidney disease, and vascular problems, and highlights the difficulties encountered in counselling and the need for further studies on CKD in pregnancy.

Erythropoiesis and chronic kidney disease-related anemia: From physiology to new therapeutic advancements.

Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia-inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in-depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis-stimulating agents.

Emerging therapeutic strategies for minimal change disease and focal and segmental glomerulosclerosis.

INTRODUCTION: Minimal change disease (MCD) and Focal and segmental glomerulosclerosis (FSGS) are two of the major causes of nephrotic syndrome (NS) in children and adults. According to KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, the treatment of adult primary MCD and FSGS should be based on immunosuppressants and antiproteinuric drugs. Recently, Rituximab, a humanized monoclonal antibody (mAb) has emerged as a potential treatment for steroid or calcineurin inhibitor-dependent patients; it has however demonstrated lower efficacy in those with nephrotic syndrome that is resistant to the above indicated drugs. AREAS COVERED: Analysis of ongoing and already completed clinical trials, retrieved from clinicaltrials.gov, clinicaltrialsregister.eu and PubMed involving new therapies for nephrotic syndrome secondary to MCD and FSGS. EXPERT OPINION: The most promising drugs under investigation for MCD and FSGS are mAbs. We are hopeful that new therapeutic options to treat multi-drug resistant MCD and FSGS will emerge from currently ongoing studies. What appears certain is the difficulty in enrolling patients affected by orphan renal diseases and the selection of valid endpoints in clinical trials, such as kidney failure.

Convective Dialysis Reduces Mortality Risk: Results From a Large Observational, Population-Based Analysis.

According to many studies, extracorporeal dialysis with convective methods is associated with better clinical outcomes and a survival benefit compared to diffusive techniques. However, there is no full agreement on the actual superiority of this kind of renal replacement therapy on hard end-points such as mortality. We performed a retrospective epidemiological cohort study to provide "real-world" evidence on the impact of convective and non-convective dialysis techniques on all-cause and cardiac mortality and biochemical outcomes among dialysis patients in Sicily, the southernmost region of Italy. Data of all incident adult patients (N = 6529) who have started chronic extracorporeal dialysis over the period 2009-2015 were retrieved from the Sicilian Registry of Nephrology, Dialysis and Transplantation. There were 1558 patients receiving convective techniques (23.86%). Overall mortality rate was 45.21% with a significant difference between convective (31.39%) and non-convective (49.55%) groups (P < 0.0001). After adjustment for potential confounders in multiple Cox regression models of increasing complexity, the mortality risk remained significantly lower for patients treated with convective methods (HR, 0.581; 95%CI, 0.525 to 0.643; P < 0.0001). Moreover, the convective group had a better blood chemistry profile, improved dialysis efficacy, and reduced mortality rate from cardiac diseases compared to the non-convective group. As a sensitivity analysis, patients were categorized according to propensity score quartiles and the hazard ratio for both all-cause and cardiac mortality was significantly lower for the convective group in each quartile. In conclusion, despite the observational and retrospective design, the results of the present study further support the use of convective therapies for the treatment of end-stage renal disease.

C3 glomerulopathy in cystic fibrosis: a case report.

BACKGROUND: C3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial and subepithelial space. An abnormal systemic activation of the alternative pathway of the complement cascade is responsible for the development of the disease if triggered by several possible environmental conditions. We report the first case in literature of a patient affected by cystic fibrosis and C3GN. CASE PRESENTATION: Our case involves a young woman with cystic fibrosis, who had persistent microscopic hematuria, proteinuria and hypocomplementemia C3 for over three months. Renal biopsy confirmed the diagnosis of C3 glomerulopathy. Complement system dysregulation was tested and resulted in a strong terminal pathway activation proved by high levels of sC5b-9 complex, amounting to 1588 ng/ml (normal value < 400 ng/ml). Next generation sequencing (NGS) showed polymorphism in CFH (p.V62I in SCR1) and THBD (p.A473V), already known as pathogenic for C3GN, as well as a mutation in C3 (p.R102G) associated only with age-related macular degeneration (AMD) so far. Treatment was based on ACE inhibitors and kidney function is currently stable (GFR 50 ml/min, serum creatinine 1.7). CONCLUSIONS: The co-existence of C3 glomerulopathy in a patient with CF, which is characterized by chronic infection/inflammation, makes this case an interesting model of chronic altered systemic activation of the alternative pathway of the complement cascade.

Peripheral blood CD34+ cells as a novel and noninvasive early marker of first trimester miscarriage: results from a case-control analysis.

PURPOSE: To evaluate the levels of peripheral blood CD34+ cells in women who subsequently had a spontaneous miscarriage (SM). MATERIALS AND METHODS: We enrolled 11 women who had SM, matching them for age, BMI and gestational age with 33 healthy pregnancies (controls). From a blood sample at 9th-11th weeks of pregnancy, we evaluated PAPP-A, free ß-hCG, T (suppressor and helper), NK, B, CD34+ cells. RESULTS: In peripheral blood of women who had SM, PAPP-A and CD34+ cells were significantly lower (p < 0.001) compared to control group. CONCLUSIONS: CD34+ cell low level in peripheral blood is associated with increased risk of SM.

Acetate-free biofiltration to remove fibroblast growth factor 23 in hemodialysis patients: a pilot study.

AIM: Serum levels of 32 kDa-phosphaturic hormone fibroblast growth factor 23 (FGF23) rise early in renal failure in order to keep phosphatemia within the normal range; however, this compensatory mechanism itself contributes to chronic kidney disease-mineral bone disorder. High FGF23 is also associated to left ventricular hypertrophy, vascular calcifications and thus increased cardiovascular risk. The aim of this pilot pre-post study was to evaluate the effects of a single hemodiafiltration session with acetate-free biofiltration (AFB) on FGF23 serum levels. METHODS: Nine hemodialysis patients were enrolled; sessions were performed using the Integra® monitor (Hospal, Bologna, Italy) and a polyacrylonitrile membrane. Peripheral venous blood samples were taken before (pre-HD), at mid- and after treatment (post-HD); dialysate samples were collected by the Quantiscan™ monitoring system. FGF23 was measured by a human FGF-23 ELISA kit. Mid- and post-HD values were corrected for hemoconcentration. RESULTS: Pre-HD FGF23 levels positively correlated with dialysis vintage (r = 0.7192; p = 0.0443). They were significantly reduced by the hemodialysis session (from 2.38 ± 1.80 to 1.15 ± 1.21 ng/ml, p = 0.0171) with a reduction ratio of 52.55 ± 28.76%. FGF23 was detected in the dialysate samples. CONCLUSION: FGF23 underwent a significant reduction during AFB. Such removal was greater than that induced by conventional hemodialysis as reported in the literature (19%-decrease using modified cellulosic membranes). This difference may be attributed to the ability of AFB hemodiafiltration to efficiently remove middle molecules by convection. Whether a better clearance of FGF23 during hemodialysis may result in improved cardiovascular outcomes in the long term needs to be confirmed by randomized controlled trials.

The Myth of Water and Salt: From Aquaretics to Tenapanor.

The impact of water intake has been studied in several renal diseases. For example, increasing water intake is useful to prevent primary and secondary nephrolithiasis. In autosomal dominant polycystic kidney disease, arginine vasopressin (AVP) is involved in the progression of the disease, and water intake could play a therapeutic role by inhibiting the synthesis of AVP, but its efficacy is still controversial. Conversely, the use of aquaretics, which are antagonists of AVP V2 receptors, results in the reduction of the increase rate of total kidney volume with a slower decline of glomerular filtration rate. In chronic kidney disease, AVP contributes to glomerular hyperfiltration, arterial hypertension, and synthesis of renin, resulting in renal sclerosis. Increased water intake could reduce AVP activation determining a potential protective effect on the kidney, but its efficacy has not yet been clearly demonstrated. On the other side, sodium and potassium play an important role in the control of arterial blood pressure and are involved in the development and progression of chronic kidney disease. Reduction of sodium intake and increase of potassium intake determine a decrease of arterial blood pressure with a beneficial effect on the kidney; however, adherence to sodium restriction is very poor. Regarding this, sodium-hydrogen exchanger isoform 3 inhibitors may reduce sodium absorption in the gut. The most recent sodium-hydrogen exchanger isoform 3 inhibitor, known as tenapanor, reduces extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in experimental studies and increases fecal loss of sodium in humans.

Beneficial effects of oral pure caffeine on oxidative stress.

Ingestion of coffee (which is a mixture of over 1000 hydrosoluble substances) is known to protect from type-2 diabetes mellitus and its complications, and other chronic disorders associated with increased oxidative damage in blood and tissues. This protection is generally attributed to polyphenols and melanoidins. Very few studies were conducted on the amelioration of classic blood markers of oxidative stress induced after a few days of caffeine administration, but results vary. To assess whether caffeine per se could account for antioxidant properties of coffee in the short-term, we tested the ability of pure caffeine ingestion (5 mg/kg body weight/day in two daily doses for seven consecutive days) to improve plasma levels of six biochemical indices in healthy male volunteers (n = 15). These indices were total antioxidant capacity (TAC), glutathione (GSH), oxidized glutathione (GSSG), GSH to GSSG ratio, lipid hydroperoxides (LOOH) and malondialdehyde (MDA). We found that all indices changed significantly (P < .05 or < .01) in a favourable manner, ranging from -41% for GSSG to -70% for LHP levels, and +106% for GSH levels to +249% for the GSG/GSSG ratio. Changes of any given index were uniform across subjects, with no outliers. We conclude that caffeine has unequivocal, consistent antioxidant properties.

[Long-term outcome of renal function in women with preeclampia and pregestational diabetes]. / Rischio di danno renale a distanze in donne con preeclampsia.

Pre-eclampsia (PE) is an important cause of acute renal failure and an important risk marker for subsequent chronic kidney disease. In normal pregnancy, there are marked changes in the renin-angiotensin system (RAS) including considerably elevated angiotensin II (ang II) levels. However, vascular resistance decreases markedly during normal pregnancy, suggesting that pregnant individuals are less sensitive to ang II than non-pregnant individuals. In contrast, during PE decreased circulating components of the RAS with enhanced sensitivity of ang II infusion have been reported. Patients with a history of PE have an increased risk of microalbuminuria with a prevalence similar to subjects with type 1 diabetes mellitus. Women with gestational or chronic hypertension were at a high risk of end-stage renal disease (ESRD) vs. normotensive ones, but the risk is much greater for women who had PE or eclampsia than those who had gestational hypertension only. A previous episode of PE should suggest long-term follow-up, especially with respect to hypertension and microalbuminuria within 6-8 weeks of delivery, and should require a nephrological consult if these disorders do not resolve. Pregestational diabetes was also associated with long-term increased risk of ESRD and death. Lastly, women who have PE and give birth to offspring with low birth weight and short gestation have a substantially increased risk for having a later kidney biopsy. For all these reasons, short and long-term evaluation of kidney function should be suggested in women with previous complicated pregnancy.

Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Accruing evidence suggests that Xanthine Oxidase inhibitors (XOis) may bring direct renal benefits, besides those related to their hypo-uricemic effect. We hence aimed at performing a systematic review of randomized controlled trials (RCTs) to verify if treatment with XOis may improve renal outcomes in individuals with chronic kidney disease (CKD). METHODS: Ovid-MEDLINE, PubMed and CENTRAL databases were searched for RCTs comparing any XOi to standard therapy or placebo. The primary endpoint of interest was progression to End-Stage Kidney Disease (ESKD); secondary endpoints were changes in serum creatinine, glomerular filtration rate (eGFR), proteinuria and albuminuria. RESULTS: XOis treatment significantly reduced the risk of ESKD compared to the control (3 studies, 204 pts; RR = 0.42; 95% CI, 0.22, 0.80) and also improved eGFR in data pooled from RCTs with long follow-up times (>3 mo.) (4 studies, 357 pts; mean difference (MD) 6.82 mL/min/1.73 m²; 95% CI, 3.50, 10.15) and high methodological quality (blind design) (3 studies, 400 pts; MD 2.61 mL/min/1.73 m²; 95% CI, 0.23, 4.99). Conversely, no definite effects were apparently noticed on serum creatinine, proteinuria and albuminuria. CONCLUSIONS: XOis may represent a promising tool for retarding disease progression in CKD patients. Future trials are awaited to confirm the generalizability of these findings to the whole CKD population.

Cystic Fibrosis: A Risk Condition for Renal Disease.

OBJECTIVE: Cystic fibrosis (CF) is the most common autosomal recessive disease affecting the Caucasian population, with a birth incidence ranging between 1:2,500 and 1:1,800. It is caused by mutations in the CF transmembrane regulator gene which is localized on 7 chromosomes. Renal disease is reported as a relatively rare complication in adult patient with CF. We evaluated proteinuria and chronic renal failure (CRF) in a population of patients with CF. METHODS: A retrospective study was carried out in a referral center for CF at University of Messina in Italy. We identified all patients with renal disease, characterized by proteinuria and/or CRF, during the period 2007 to 2012 and reviewed their medical records to assess influence on renal disease of genotype, number of pulmonary exacerbation, pancreatic insufficiency, pulmonary function, CF-related diabetes, and antibiotics courses. RESULTS: From a population of 77 adult patients with CF, we identified 9 patients with proteinuria (11.7%), and 11 patients (14.28%) with CRF. Mean age was 35.6 (+5.1 standard deviation) years, 55% were female and 33% had diabetes mellitus. Renal biopsy was performed in 3 patients because of nephrotic syndrome in 1 patient and proteinuria with renal failure in the other 2 patients. Renal amyloidosis was disclosed in 2, whereas IgA nephropathy in 1 patient. The ΔF508 mutation in homozygosis was present in 44% of patients with proteinuria (vs. 27% of our CF population, relative risk 2.07), whereas genotype ΔF508/N1303K in 22%. ΔF508 allele mutation was present in 77.7% of proteinuric patients. CONCLUSIONS: Our study shows a higher prevalence of renal disease in patients with CF, than was previously described. The main reason may be related to increased life expectancy because of better management. Moreover, patients with ΔF508 homozygosis had higher risk of proteinuria.

The relationship between coping, emotion regulation, and quality of life of patients on dialysis.

Previous studies have investigated constructs that facilitate adaptation to chronic disease and improve quality of life and constructs that lead to psychopathological complications. The purpose of this research is to investigate the impact of coping and emotional regulation on the quality of life of patients on dialysis. Three questionnaires were administered to 78 patients on dialysis: Coping Orientations to Problems Experienced, Short Form (36), and Cognitive Emotion Regulation Questionnaire. Regressions analyses indicated that age, Rumination, Positive Refocusing, Avoidance Strategies, Approach to the Problem, and Transcendent Orientation predicted Physical Health. With regard to Mental Health, the predictors were gender, Self-Blame, Acceptance, Rumination, Positive Reappraisal, Catastrophizing, Avoidance Strategies, and Transcendent Orientation. This study confirms the relationship between emotional regulation, coping, and quality of life. The results highlight the need for total care of the patients, including an assessment of both physical state and psychological functioning in order to promote total well-being.

[Complement factor B mutation in atypical hemolytic uremic syndrome. Rare cause of rare disease].

Hemolytic uremic syndrome (HUS) is a rare disease characterized by microangiopathic hemolysis, platelet consumption and multiple organ failure with predominant renal involvement. In the most of cases (85-90%), it is associated with enteric infection due to Shiga-toxin or verocytotoxin (STEC-VTEC)-producer Escherichia coli. Rarely, in about 10-15% of cases, HUS develops in the presence of a disorder of alternative complement pathway regulation and it is defined atypical (aHUS). We describe the case of a 65-year-old man who came to our attention with a clinical presentation of aHUS and a clinical course characterized by rapidly progressive acute renal failure (ARF), which required renal replacement treatments, and by a stable clinical picture of hematological impairment as a marker of a non-severe and self-limiting form. The clinical and laboratory course allowed us not to perform specific therapies such as plasma exchange and/or block of the complement with eculizumab. Less than two weeks after hospital admission, there was a gradual recovery of renal function with spontaneous diuresis and hematological remission. Genetic screening has revealed a heterozygous mutation in the complement factor B (CFB) that is not described in the literature and therefore not yet characterized in the genotype/phenotype correlation, also for the extreme rarity of the forms associated with CFB alteration. In conclusion, the presence of a new mutation in the CFB, such as the one described in our case, is probably associated with the development of aHUS but has not led to a poor prognosis, as generally reported in the literature for known variants of the CFB.