Calculation of Kidney Volumes with Magnetic Resonance in Patients with Autosomal Dominant Polycystic Kidney Disease: Comparison between Methods.

Autosomal dominant polycystic renal disease (ADPKD) is the most frequent kidney inheritable disease, characterized by the presence of numerous bilateral renal cysts, causing a progressive increase in total kidney volume (TKV) and a progressive loss of renal function. Several methods can be used to measure TKV by using MRI, and they differ in complexity, accuracy and time consumption. This study was performed to assess the performance of the ellipsoid method and the semi-automatic segmentation method, both for TKV and SKV (single kidney volume) computation. In total, 40 patients were enrolled, and 78 polycystic kidneys analyzed. Two independent operators with different levels of experience evaluated renal volumetry using both methods. Mean error for ellipsoid method for SKV computation was -2.74 ± 11.79% and 3.25 ± 10.02% for the expert and the beginner operator, respectively (p = 0.0008). A Wilcoxon test showed a statistically significant difference between the two operators for both methods (SKV p = 0.0371 and 0.0034; TKV p = 0.0416 and 0.0171 for the expert and the beginner operator, respectively). No inter-operator significant difference was found for the semi-automatic method, in contrast to the ellipsoid method. Both with a Wilcoxon test and Bland-Altman plot, statistically significant differences were found when comparing SKV and TKV measurements obtained with the two methods for both operators, even if the differences are stronger for the beginner operator than for the expert one. The semi-automatic segmentation method showed more inter-observer reproducibility. The ellipsoid method, in contrast, appears to be affected by greater inter-observer variability, especially when performed by operators with limited experience.

Previous therapy with immune checkpoint inhibitor as a cause of hypothyroidism, myositis, and renal insufficiency in a candidate for allogeneic hematopoietic transplantation.

Treatment of neoplastic diseases resistant to conventional chemotherapies is still an open challenge. The increasing development of chemical molecules or monoclonal antibodies able to recognize precise molecular targets of cancer disease has played an increasingly important role in treating patients suffering from solid or hematological tumors, and constitutes the basis of so-called 'targeted therapy'. Immunotherapy has become a cornerstone for treating refractory or relapsed cancer disease patients after standard chemotherapies. Immune checkpoint (including PD-1) inhibitors are essential drugs that significantly improve the therapeutic possibilities for neoplastic patients. Still, foreseeable or unpredictable adverse effects can potentially arise during or after the end of therapy. Specifically, toxicity involving several organs is capable of delaying or preventing the continuation of programmed treatment, as described in this case, where we will discuss the possibility of toxicity affecting various organs (kidney, muscle tissue, and thyroid) attributed to nivolumab and which resulted in temporary ineligibility for allogeneic transplantation.

SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM).

The increasing number of examinations and interventional radiological procedures that require the administration of contrast medium (CM) in patients at risk for advanced age and/or comorbidities highlights the problem of CM-induced renal toxicity. A multidisciplinary group consisting of specialists of different disciplines-radiologists, nephrologists and oncologists, members of the respective Italian Scientific Societies-agreed to draw up this position paper, to assist clinicians increasingly facing the challenges posed by CM-related renal dysfunction in their daily clinical practice.The major risk factor for acute renal failure following CM administration (post-CM AKI) is the preexistence of renal failure, particularly when associated with diabetes, heart failure or cancer.In accordance with the recent guidelines ESUR, the present document reaffirms the importance of renal risk assessment through the evaluation of the renal function (eGFR) measured on serum creatinine and defines the renal risk cutoff when the eGFR is < 30 ml/min/1.73 m2 for procedures with intravenous (i.v.) or intra-arterial (i.a.) administration of CM with renal contact at the second passage (i.e., after CM dilution with the passage into the pulmonary circulation).The cutoff of renal risk is considered an eGFR < 45 ml/min/1.73 m2 in patients undergoing i.a. administration with first-pass renal contact (CM injected directly into the renal arteries or in the arterial district upstream of the renal circulation) or in particularly unstable patients such as those admitted to the ICU.Intravenous hydration using either saline or Na bicarbonate solution before and after CM administration represents the most effective preventive measure in patients at risk of post-CM AKI. In the case of urgency, the infusion of 1.4% sodium bicarbonate pre- and post-CM may be more appropriate than the administration of saline.In cancer patients undergoing computed tomography, pre- and post-CM hydration should be performed when the eGFR is < 30 ml/min/1.73 m2 and it is also advisable to maintain a 5 to 7 days interval with respect to the administration of cisplatin and to wait 14 days before administering zoledronic acid.In patients with more severe renal risk (i.e., with eGFR < 20 ml/min/1.73 m2), particularly if undergoing cardiological interventional procedures, the prevention of post-CM AKI should be implemented through an internal protocol shared between the specialists who treat the patient.In magnetic resonance imaging (MRI) using gadolinium CM, there is a lower risk of AKI than with iodinated CM, particularly if doses < 0.1 mmol/kg body weight are used and in patients with eGFR > 30 ml/min/1.73 m2. Dialysis after MRI is indicated only in patients already undergoing chronic dialysis treatment to reduce the potential risk of systemic nephrogenic fibrosis.

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial.

BACKGROUND: A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking. METHODS: We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events. RESULTS: At 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen. CONCLUSIONS: This pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO), NCT03018535.

[Therapeutic options to reduce arterial stiffness in chronic kidney disease].

Chronic kidney disease is associated with an increased cardiovascular risk. Several uremic toxins are also vascular toxins and may contribute to the increase of the cardiovascular risk through the development of aortic stiffening. In this process, oxidative stress and endothelial dysfunction play an important role. Considering that aortic stiffness is a known cardiovascular risk factor and a vascular biomarker involved in the development of chronic cardiac dysfunction, and that the reduction of aortic stiffness is associated with an improved survival of patients with end-stage kidney disease, we aim at reviewing the therapeutic options to reduce aortic stiffness and potentially the cardiovascular risk.

Renal involvement in primary antiphospholipid syndrome.

Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy-related problems associated with persistently elevated levels of antiphospholipid antibodies. The kidney is a major target organ in both primary and secondary antiphospholipid syndrome. This review describes several aspects of the renal involvement in the primary form of the syndrome, in particular the histological pattern of the so-called antiphospholipid syndrome nephropathy (APSN). APSN is a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries, recanalizing thrombi in arteries and arterioles, and focal atrophy, a constellation of morphological lesions suggestive of primary antiphospholipid syndrome.

[Genetic approach to hypertensive nephrosclerosis]. / Approccio genetico alla nefroangiosclerosi.

Several epidemiological and experimental studies suggest an important role of genetic factors in the pathogenesis of hypertensive nephrosclerosis. However, identification of susceptibility genes is difficult. The association between apolipoprotein L1 gene (APOL1) variants and non-diabetic chronic kidney disease in African Americans has modified the approach to hypertensive glomerular sclerosis, as a member of a single disease spectrum: APOL1-associated FSGS.

Non-hemodynamically significant renal artery stenosis predicts cardiovascular events in persons with ischemic heart disease.

BACKGROUND/AIMS: Recently, we reported that small renal arteries, defined by a low reference diameter (RD) or minimal luminal diameter (MD), are independently associated with a low GFR, resistant hypertension, and onset of contrast-induced nephropathy and suggested a post-hoc analysis of CORAL trial based on RD categories. Here we hypothesized that RD and MD are markers of nontraditional cardiovascular risk factors and tested whether low RD and MD could impact the prognosis of patients with ischemic heart disease. METHODS: Prospective cohort study. We used proportional hazards models to analyze the first onset of cardiovascular events in relation with RD, MD, or percentage of renal artery stenosis (RAS) in those with low-to-moderate RAS (10-70%) (n = 181). RESULTS: During the median follow-up of 4.5 (range, 0.1-5) years, 27.8% participants (n = 623; mean age, 64 years; 29% women) experienced a cardiovascular event (35.4% in those with RAS 10-70%). The presence of low-to-moderate RAS was associated with cardiovascular events. In these subjects, those with low MD were associated with a higher risk of cardiovascular events (MD >4.2 mm, HR: 1; MD 3.2-4.2 mm, HR: 1.66, 95% CI: 0.74-3.72, p = 0.22; MD <3.2 mm, HR: 3.72, 95% CI: 1.65-8.40, p = 0.002). When MD was added to a standard risk-factor model, risk prediction improvement was by 4.1%. Results were qualitatively similar if MD was replaced by RD or percentage of stenosis, but with smaller improvement of risk prediction and model fit. CONCLUSIONS: In patients with ischemic heart disease and low-to-moderate RAS, MD is a significant predictor of cardiovascular events, improves risk prediction, and may represent a valuable biomarker of cardiovascular disease risk.

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.

EuroSCORE II versus additive and logistic EuroSCORE in patients undergoing percutaneous coronary intervention.

The aim of the present study was to externally validate the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (ESII) in patients undergoing percutaneous coronary intervention (PCI) and to compare its performance with that of its previously released versions, named additive (addES) and logistic EuroSCORE (logES). A total of 537 patients undergoing PCI were analyzed by different measurements of discrimination, calibration, and global accuracy. A significant gradient in all-cause mortality was seen with all the models at 30 days, 1 year, and 5 years, with the exception of the ESII at 30 days. The ESII had the lowest area under the receiver operating characteristic curve at all time points compared with its previous version, being 0.83 (vs 0.90 for both addES and logES) at 30 days, 0.75 (vs 0.82 for both addES and logES) at 1 year, and 0.69 (vs 0.77 for addES and 0.76 for logES) at 5 years. However, the ESII displayed a better calibration than the logES at 30 days, whereas both scores were miscalibrated at 1 and 5 years. The Brier score displayed similar global accuracy between the ESII and logES. In conclusion, the ESII is better calibrated than the logES at 30 days but does not represent a step forward in discrimination and global accuracy compared with its previous versions for predicting early- and long-term mortality of patients undergoing PCI.

Incorporating glomerular filtration rate or creatinine clearance by the modification of diet in renal disease equation or the Cockcroft-Gault equations to improve the global accuracy of the Age, Creatinine, Ejection Fraction [ACEF] score in patients undergoing percutaneous coronary intervention.

BACKGROUND: The aim of the present study was to appraise the comparative ability of different ACEF models incorporating glomerular filtration rate or creatinine clearance estimated by the Modification of Diet in Renal Disease [ACEFMDRD] or Cokcroft-Gault [ACEFCG] equations, respectively, over the original ACEF score (ACEFSrCr) in patients undergoing percutaneous coronary intervention (PCI). METHODS: A total of 537 patients were analyzed by different measures of discrimination, calibration and net reclassification improvement (NRI). RESULTS: A significant gradient in all-cause mortality was consistently seen with all the models at 30 days, 1 year and 5 years. The comparison of the three models showed that the best balance in terms of discrimination and calibration for all-cause mortality was offered by the ACEFCG at 30 days, the ACEFMDRD at 1 year and similarly by the ACEFCG and ACEFMDRD at 5 years. At 30 days, the NRI was +32.9% for ACEFMDRD over ACEFSrCr and +16% for ACEFCG over ACEFSrCr. At 1 year, the NRI was 13.8% for ACEFMDRD over ACEFSrCr and -7.8% for ACEFCG over ACEFSrCr. At 5 years, the NRI was +7.7% for both the ACEFMDRD and the ACEFCG over the ACEFSrCr. CONCLUSIONS: In patients undergoing PCI, the ACEF score is associated with satisfactory early-, mid- and long-term discrimination regardless of the definition of renal function. However, incorporating glomerular filtration rate or creatinine clearance by the MDRD or CG formulas in the ACEF score yields superior calibration compared with the original SrCr-based equation, with the ACEFMDRD displaying superior reclassification ability over the ACEFCG and ACEFSrCr at 30 days and 1 year.

Prevalence of renal artery stenosis in patients undergoing cardiac catheterization.

To investigate the prevalence of significant renal artery stenosis (RAS ≥50%), and to identify clinical predictors for significant RAS in patients with an elevated cardiovascular risk, such as those affected by ischemic heart disease. In patients with an elevated cardio-vascular risk, both atherosclerotic renovascular disease and coronary artery disease (CAD) are likely to occur. Prospectively from April 2007 to March 2008, all consecutive patients with ischemic heart disease undergoing non-emergent cardiac catheterization were also evaluated for atherosclerotic RAS by renal arteriography. A RAS ≥50% was considered as significant. A total of 1,298 patients underwent cardiac and renal angiography. Significant RAS was found in 70 out of 1,298 patients (5.4%). The presence of peripheral vascular disease, eGFR <67 ml/min/1.73 m(2), age >66 years, dyslipidemia, CAD severity and pulse pressure >52 mmHg were independent clinical predictors of significant RAS, and jointly produced a ROC AUC of 0.79 (95% CI 0.73-0.85, P < 0.001). Based on these data, a prediction rule for significant RAS was developed, and it showed an adequate predictive performance with 64% sensitivity and 82% specificity. In a large cohort of patients undergoing coronary angiography, significant RAS is a relatively rare comorbidity (5.4%). A model based on simple clinical variables may be useful for the clinical identification of high CV risk patients who may be suitable for renal arteriography at the time of cardiac catheterization.

[Hypertensive nephrosclerosis: an exhaustive diagnosis?]. / Nefroangiosclerosi: entita' clinica definita?

Hypertensive nephrosclerosis is a much overused clinical diagnosis, largely unsubstantiated by biopsy data. It is in fact a clinical-pathological diagnosis implying a causal role of hypertension in the associated chronic kidney disease. However, such a simple, linear causality is often not obvious or easy to demonstrate. Further factors like age, Afro-American descent, genetic and immunological factors as well as dysmetabolic syndrome may contribute to the development and progression of arterionephrosclerosis independently of hypertension.

Chest ultrasound and hidden lung congestion in peritoneal dialysis patients.

BACKGROUND: Chest ultrasound (US) is a non-invasive well-validated technique for estimating extravascular lung water (LW) in patients with heart diseases and in end-stage renal disease. We systematically applied this technique to the whole peritoneal dialysis (PD) population of five dialysis units. METHODS: We studied the cross-sectional association between LW, echocardiographic parameters, clinical [pedal oedema, New York Heart Association (NYHA) class] and bioelectrical impedance analysis (BIA) markers of volume status in 88 PD patients. RESULTS: Moderate to severe lung congestion was evident in 41 (46%) patients. Ejection fraction was the echocardiographic parameter with the strongest independent association with LW (r = -0.40 P = 0.002). Oedema did not associate with LW on univariate and multivariate analysis. NYHA class was slightly associated with LW (r = 0.21 P = 0.05). Among patients with severe lung congestion, only 27% had pedal oedema and the majority (57%) had no dyspnoea (NYHA Class I). Similarly, the prevalence of patients with BIA, evidence of volume excess was small (11%) and not significantly different (P = 0.79) from that observed in patients with mild or no congestion (9%). CONCLUSIONS: In PD patients, LW by chest US reveals moderate to severe lung congestion in a significant proportion of asymptomatic patients. Intervention studies are necessary to prove the usefulness of chest US for optimizing the control of fluid excess in PD patients.

Effect of renal artery stenting on left ventricular mass: a randomized clinical trial.

BACKGROUND: Whether renal revascularization reduces left ventricular hypertrophy in patients with coronary artery disease is uncertain. STUDY DESIGN: Randomized clinical trial testing the effect of renal artery stenting versus medical therapy on left ventricular hypertrophy progression in patients affected by ischemic heart disease and renal artery stenosis. SETTING & PARTICIPANTS: Incident patients with ischemic heart disease undergoing cardiac catheterization with renal artery stenosis >50%-≤80%. INTERVENTION: Revascularization plus standard medical therapy versus medical therapy alone. OUTCOMES: Primary end point was change in echocardiographic left ventricular mass index (LVMI). MEASUREMENTS: Clinical and echocardiographic studies were performed at baseline and after 1 year. RESULTS: 84 patients were randomly assigned: 43 to revascularization plus standard medical therapy and 41 to medical therapy alone. At baseline, clinical characteristics were similar in the 2 study groups. After 1 year, there was no statistically significant difference between longitudinal change in the medical therapy group versus that in the medical therapy plus revascularization group for LVMI (2.1; 95% CI, -6.1 to 10.3 g/m(2)), blood pressure (systolic, -0.2 [95% CI, -9.1 to 8.8 mm Hg]; diastolic, -3.3 [95% CI, -8.4 to 1.8 mm Hg]), or estimated glomerular filtration rate (1.5; 95% CI, -5.8 to 8.9 mL/min/1.73 m(2)). The number of major cardiovascular events was similar in the 2 groups (revascularization plus standard medical therapy [fatal, n = 2; nonfatal, n = 11] and medical therapy alone [fatal, n = 2; nonfatal, n = 11]). LIMITATIONS: Patients with very severe renal artery stenosis were excluded from the study. CONCLUSIONS: Our study was unable to detect a clinically significant benefit of renal revascularization on LVMI in patients with coronary artery disease and renal artery stenosis of 50%-80%.

Renal artery diameter, renal function and resistant hypertension in patients with low-to-moderate renal artery stenosis.

BACKGROUND: Atherosclerotic renovascular disease is associated with resistant hypertension and chronic kidney disease, although the causal relationship is discussed. To date, the role of renal artery diameter on these pathological conditions was not clearly studied. We aimed to identify the association of reference diameter and minimal luminal renal artery diameter with glomerular filtration rate (GFR) and resistant hypertension in a high cardiovascular risk population. METHODS: In this cross-sectional, single-center study, we enrolled 734 patients who underwent a renal angiography immediately after a coronary angiography indicated for a diagnosis of ischemic heart disease. RESULTS: Mean age was 64 ±â€Š10 years (men 72%). GFR was 79 ±â€Š22 ml/min per 1.73 m(2). Five hundred and eighteen patients had no luminal narrowing and 216 patients had low-to-moderate luminal narrowing (10-70%, mean 36%). A positive significant association between reference diameter and GFR was detected in patients without luminal narrowing [beta 2.2 ml/min per 1.73 m(2) for 1 mm increase, 95% confidence interval (CI) 0.3-4.0, P < 0.05] and in those with low-to-moderate luminal narrowing (beta 7.7 ml/min per 1.73 m(2) for 1 mm increase, 95% CI 4.2-11.1, P < 0.001). The lowest quartile of reference diameter (<5.2 mm) was associated with GFR less than 60 ml/min per 1.73 m(2) [odds ratio (OR) 3.18, 95% CI 1.61-6.29, P < 0.001]. Patients with resistant hypertension had low minimal diameter and reference diameter. Reference diameter less than 5.2 mm was associated with an increased risk of resistant hypertension (OR 2.63, 95% CI 1.02-6.77, P < 0.05). CONCLUSIONS: Small renal arteries, defined by a low reference diameter or minimal luminal diameter, are independently associated with low GFR and resistant hypertension, independent of the degree of stenosis and major confounders.

Women and the sciences.

The education level of women has increased significantly in recent decades. However, although there is a continued positive trend overall, women remain underrepresented (or misrepresented?) in the main fields of science. In Europe the proportion of women in scientific research is growing faster than that of men, but women are more likely than men to choose education, arts and humanities, health and welfare. Moreover, of the total number of women graduating in all faculties (55%), the percentage of women graduating in medicine is 65%-68%, in Europe as in the United States. As far as nephrology is concerned, unpublished data from the Italian Society of Nephrology indicate that female nephrologists make up almost 30% of the total number in the age group between 40 and 55, and this proportion is even higher in the age group younger than 40 years. In comparison with the past, there are some hints that things are going to change, but the path is still a difficult one, much effort is needed and there is a long way ahead.