[High-flow fistula: a problem not easy to handle].

High-output cardiac failure is a well-known phenomenon of high-flow fistula in hemodialysis patients. The definition of "high flow" is varied and almost always connected to proximal arteriovenous fistulas (AVF). High flow access is a condition in which hemodynamics is affected by a greater rate of blood flow required for hemodialysis and this can compromise circulatory dynamics, particularly in the elderly in the context of pre-existing heart disease. High access flow is associated with complications like high output heart failure, pulmonary hypertension, massively dilated fistula, central vein stenosis, dialysis associated steal syndrome or distal hypoperfusion ischemic syndrome. Although there is no single agreement about the values of AVF flow volume, nor about the definition of high-flow AVF, there is no doubt that AVF flow should be considered too high if signs of cardiac failure develop. The exact threshold for defining high flow access has not been validated or universally accepted by the guidelines, although a vascular access flow rate of 1 to 1.5 l/min has been suggested. Moreover, even lower values may be indicative of relatively excessive blood flow, depending on the patient's condition. The pathophysiology contributing to this disease process is the shunting of blood from the high-resistance arterial system into the lower resistance venous system, increasing the venous return up to cardiac failure. Accurate and well-timed diagnosis of high flow arteriovenous hemodynamics by monitoring of blood flow of fistula and cardiac function is required in order to stop this process prior to cardiac failure. We present two cases of patients with high flow arteriovenous fistula with a review of the literature.

[CEUS, a world to discover. Three clinical cases and literature review].

Currently, CEUS (Contrast-Enhanced UltraSound) is used in the evaluation of different organs and systems. It offers valuable information about vascular disease, both on a macro- and a micro-vascular level, and has a series of well-established applications in the monitoring of adult patients; official guidelines and recommendations are also available. Its use in a nephrological setting is constantly growing thanks to the lack of nephrotoxicity of the contrast agent, the absence of ionizing radiation and the possibility of characterizing focal pathologies, for diagnosis and in clinical practice. We describe here 3 clinical cases relating to renal diseases and we review the relevant literature with a specific focus on the use of CEUS in a nephro-urological setting.

[Evaluation via ecocolordoppler before creating a vascular access for hemodyalisis: a monocentric experience].

The use of a preoperative echocolordoppler improves the clinical evaluation because provides anatomical and hemodynamic information that make it an important tool in planning vascular access strategy. The preoperative ultrasound study of the vessels can significantly reduce the failure rate and the incidence of complications of vascular access. We describe the experience of our center, lasting 10-year, where the ultrasound assessment was performed in all patients before the creation of vascular access. Indeed, ultrasound reduces the rate of fistula failure and increases the utilization of fistula, allowing proper selection of vessels. In addition, the presence of the vascular access team has allowed us to achieve quite satisfactory results.

Left ventricular dysfunction in ADPKD and effects of octreotide-LAR: A cross-sectional and longitudinal substudy of the ALADIN trial.

BACKGROUND AND AIM: In autosomal dominant polycystic kidney disease (ADPKD) cardiac abnormalities have been observed before the onset of hypertension or renal dysfunction. We sought to characterize, in ADPKD patients, left ventricular (LV) function and its changes after somatostatin-analogue octreotide-LAR treatment. METHODS: In a 1:1:1 cross-sectional study, we evaluated LV function by speckle-tracking echocardiography in 34 ADPKD patients from one ALADIN-trial center and in 34 age- and gender-matched healthy controls and 34 equally-matched renal controls with non-cystic chronic kidney disease. Changes in LV function were compared in the 16 and 18 ADPKD patients originally randomized to 3 year-treatment with octreotide-LAR or placebo, respectively. RESULTS: LV twist and untwisting rates were lower in ADPKD patients that in healthy or renal controls (6.1 ±â€¯2.6° vs. 11.1 ±â€¯2.1° and 10.2 ±â€¯3.7°; -49.5 ±â€¯18.1°/s vs. -79.8 ±â€¯12.2°/s and -84.3 ±â€¯25.9°/s, respectively, all p < 0.001). The correlation between LV mass or diastolic BP and untwisting rate was positive in ADPKD patients (r = 0.38, p = 0.025 and r = 0.44, p = 0.011, respectively), not significant in healthy controls and negative in renal controls (r = -0.38; p = 0.023 and r = -0.40, p = 0.012, respectively. LV untwisting rate improved from -49.9 ±â€¯18.6°/s to -70.3 ±â€¯27.5°/s with octreotide-LAR, but did not change with placebo (p = 0.027 for treatment effect). At adjusted linear regression analysis, octreotide-LAR therapy emerged as the only independent predictor of untwisting rate improvement at final visit [beta coefficient -0.504 (95% CI -46.905--6.367), p = 0.014]. CONCLUSIONS: In ADPKD patients LV function is early impaired. Somatostatin-analogue therapy might help in preventing or ameliorating LV dysfunction in this population. Clinical Trial Registration http://www.clinicaltrials.gov, NCT0030928.

[Retroperitoneal renal hemorrhage: experience of our dialysis center].

The aging of the uremic population, the increasingly common use of anticoagulants, antiplatelet agents e heparin, during hemodialysis, can expose our patients to a greatest risk of bleeding. Spontaneous retroperitoneal hematomas are a fairly rare and potentially fatal condition. We describe 5 clinical cases of retroperitoneal hemorrhage that we observed during 10 years in our department, focusing on modalities of symptom onset, clinical-laboratory picture and treatment modalities.

Data on the assessment of LV mechanics by speckle tracking echocardiography in ADPKD patients.

In this article, we report anthropometric, clinical and laboratory data from Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with mild to moderate renal dysfunction and normal LV ejection fraction and from age- and sex-matched healthy controls and renal controls. Factors influencing LV untwisting rate in the group of ADPKD patients are also reported. For further interpretation and discussion please refer to the research article "Left ventricular dysfunction in ADPKD and effects of Octreotide-LAR: a cross-sectional and longitudinal sub study of the ALADIN trial" (Spinelli et al., 2018) [1].

Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy.

The clinical course of IgA nephropathy (IgAN) and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp) was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6%) and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144). The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6%) and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP) and diastolic (DBP) blood pressure during follow-up and treatment with either steroid (CS) or steroid plus azathioprine (CS+A) were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.

Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial.

INTRODUCTION: Iron deficiency is a common cause of anaemia in non-dialysis chronic kidney disease (ND-CKD). Controversies exist about the optimal route of administration for iron therapy. Liposomal iron, a new generation oral iron with high gastrointestinal absorption and bioavailability and a low incidence of side effects, seems to be a promising new strategy of iron replacement. Therefore, we conducted a study to determine whether liposomal iron, compared with intravenous (IV) iron, improves anaemia in ND-CKD patients. METHODS: In this randomized, open-label trial, 99 patients with CKD (stage 3-5, not on dialysis) and iron deficiency anaemia [haemoglobin (Hb) ≤12 g/dL, ferritin ≤100 ng/mL, transferrin saturation ≤25%] were assigned (2:1) to receive oral liposomal iron (30 mg/day, Group OS) or a total dose of 1000 mg of IV iron gluconate (125 mg infused weekly) (Group IV) for 3 months. The patients were followed-up for the treatment period and 1 month after drug withdrawal. The primary end point was to evaluate the effects of the two treatments on Hb levels; the iron status, compliance and adverse effects were also evaluated. RESULTS: The short-term therapy with IV iron produced a more rapid Hb increase compared with liposomal iron, although the final increase in Hb was similar with either treatment; the difference between the groups was statistically significant at the first month and such difference disappeared at the end of treatment. After iron withdrawal, Hb concentrations remained stable in Group IV, while recovered to baseline in the OS group. The replenishment of iron stores was greater in the IV group. The incidence of adverse event was significantly lower in the oral group (P < 0.001), and the adherence was similar in the two groups. CONCLUSIONS: Our study shows that oral liposomal iron is a safe and efficacious alternative to IV iron gluconate to correct anaemia in ND-CKD patients, although its effects on repletion of iron stores and on stability of Hb after drug discontinuation are lower.

Complications of native arteriovenous fistula: the role of color Doppler ultrasonography.

Color Doppler ultrasonography (CDUS) is a readily available, inexpensive and noninvasive method, which has improved the survival of native arteriovenous fistula (AVF) by increasing the early diagnosis of complications. Although angiography has been currently considered as the gold standard for imaging of vascular access abnormalities, CDUS may be superior in some aspects, since it provides information both on the morphology and on the function of vascular access and it is the only tool directly available to the nephrologist. In addition, CDUS offers the advantage of a non-invasive bedside procedure with lower costs and with no need for radiocontrast.

Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial.

BACKGROUND: Autosomal dominant polycystic kidney disease slowly progresses to end-stage renal disease and has no effective therapy. A pilot study suggested that the somatostatin analogue octreotide longacting release (LAR) could be nephroprotective in this context. We aimed to assess the effect of 3 years of octreotide-LAR treatment on kidney and cyst growth and renal function decline in participants with this disorder. METHODS: We did an academic, multicentre, randomised, single-blind, placebo-controlled, parallel-group trial in five hospitals in Italy. Adult (>18 years) patients with estimated glomerular filtration rate (GFR) of 40 mL/min per 1·73 m(2) or higher were randomly assigned (central allocation by phone with a computerised list, 1:1 ratio, stratified by centre, block size four and eight) to 3 year treatment with two 20 mg intramuscular injections of octreotide-LAR (n=40) or 0·9% sodium chloride solution (n=39) every 28 days. Study physicians and nurses were aware of the allocated group; participants and outcome assessors were masked to allocation. The primary endpoint was change in total kidney volume (TKV), measured by MRI, at 1 year and 3 year follow-up. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, NCT00309283. FINDINGS: Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up, at this timepoint, mean TKV increased significantly less in the octreotide-LAR group (46·2 mL, SE 18·2) compared with the placebo group (143·7 mL, 26·0; p=0·032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220·1 mL, 49·1) was numerically smaller than in the placebo group (454·3 mL, 80·8), but the difference was not significant (p=0·25). 37 (92·5%) participants in the octreotide-LAR group and 32 (82·1%) in the placebo group had at least one adverse event (p=0·16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related. INTERPRETATION: These findings provide the background for large randomised controlled trials to test the protective effect of somatostatin analogues against renal function loss and progression to end-stage kidney disease. FUNDING: Polycystic Kidney Disease Foundation.

[Fabry's disease: a comparison of the effectiveness of two different enzyme replacement therapies]. / Malattia di Fabry: ERT a confronto.

INTRODUCTION: Anderson-Fabry disease (AFD) is a multiorgan X-linked lysosomal storage disease that particularly affects the heart, kidneys, and cerebrovascular system. Current treatment is with enzyme replacement therapy (ERT), using either beta-galactosidase ('Fabrazyme') or alpha-galactosidase ('Replagal'). From June 2009, it was recommended that patients switch to alpha-galactosidase due to a manufacturing shortage of beta-galactosidase. This study assesses the effect of switching to alpha-galactosidase on clinical outcomes in patients with AFD previously treated with beta-galactosidase. PATIENTS AND METHODS: Ten patients (seven male, three female) with genetically confirmed AFD and at least 48 months continuous data collected during treatment with beta-galactosidase 1 mg/kg every other week, were switched to alpha-galactosidase 0.2 mg/kg every other week for at least 20 months, with prospective clinical evaluations performed every 6 months. Pre-switch data was collected retrospectively from patient charts. Cardiac functional parameters were assessed using magnetic resonance imaging. RESULTS: Results showed that renal function generally remained stable after the switch. Cardiac mass had already decreased significantly (p < 0.05 vs pre-ERT) after introduction of beta-galactosidase and remained unchanged after switching to alpha-galactosidase. Symptoms of pain and health status scores did not deteriorate during alpha-galactosidase therapy. Adverse events were mostly mild and infusion -related. DISCUSSION: In conclusion, switching to alpha-galactosidse was generally well tolerated and associated with stable clinical status and preservation of both renal and cardiac function.

[Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature]. / Terapia enzimatica sostitutiva in pazienti con malattia di Fabry.

Anderson-Fabry disease is a hereditary X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha galactosidase A. It results in the accumulation of the glycosphingolypid globotrioasoyl ceramide (Gb3 in different cells and organs, resulting in a multi-system pathology including end organ failure. Patients with Fabry disease present clinically with cardiac, renal and neurological involvement; both life expectancy and quality of life are severely compromised. The current causal treatment for Fabry disease is enzyme replacement therapy (ERT), available since 2001. The two recombinant preparations available for ERT are agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). They have both been showed to have positive effect on kidney and heart, on the symptoms of pain and quality of life. Few data to date are available on comparison of the two preparations of ERT. This article reviews evidence of the literature and shows our personal experience about the safety and efficacy of ERT.

[Liposomial iron: a new proposal for the treatment of anaemia in chronic kidney disease]. / Il ferro liposomiale: una nuova proposta per il trattamento dell'anemia nei pazienti affetti da insufficenza renale cronica.

Iron supplementation is essential for the treatment of anemia in the chronic kidney disease (CKD) population. Liposomial iron is a preparation of ferric pyrophosphate carried within a phospholipidic membrane. Compared to other oral formulations, it is well absorbed from the gut and demonstrates high bioavailability together with a lower incidence of side effects. The aim of our study was to evaluate the effectiveness of treatment with liposomial iron compared to intravenous iron in a CKD population with anemia and iron deficiency. Our study is a single-center, prospective, randomized, fourth-phase study. Enrollment for the study began in October 2011 and CKD 3, 4 and 5 patients were randomized to receive either intravenous iron or liposomial iron in a 1:2 ratio. The primary outcome was set as the increase of hemoglobin from baseline. The secondary outcomes were the reduction of erythropoietin dosage by at least 25% in patients treated with erythropoiesis-stimulating agents and an increase in serum ferritin of 100 ng/ml from baseline values. In the preliminary study, 21 patients were analyzed, 14 of whom were treated with oral liposomial iron and 7 with intravenous iron. The observed increase of hemoglobin at 8 weeks compared to baseline was similar in both groups but was significant in the liposomial group only.

Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature.

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency of the hydrolytic enzyme alpha galactosidase A, with consequent accumulation of globotrioasoyl ceramide in cells and tissues of the body, resulting in a multi-system pathology including end organ failure. In the classical phenotype, cardiac failure, renal failure and stroke result in a reduced median life expectancy. The current causal treatment for Fabry disease is the enzyme replacement therapy (ERT): two different products, Replagal (agalsidase alfa) and Fabrazyme (agalsidase beta), have been commercially available in Europe for almost 10 years and they are both indicated for long-term treatment. In fact, clinical trials, observational studies and registry data have provided many evidences for safety and efficacy of ERT in improving symptoms of pain, gastrointestinal disturbances, hypohidrosis, left ventricular mass index, glomerular filtration rate and quality of life. Few data are available on comparison of the two treatments and on the clinical course of the disease. This article reviews the published evidence for clinical efficacy of the two available enzyme preparations.

A novel GLA mutation in a Fabry family with glucose-6-phosphate dehydrogenase deficiency.

Fabry disease is an X-linked lysosomal disease caused by mutations of the alpha-galactosidase A (GLA) gene at chromosome subband Xq22.1. To date, more than 600 genetic mutations have been identified to determine the nature and frequency of the molecular lesions causing the classical and milder variant phenotypes and for precise carrier detection. We report here a Fabry family (mother, son and daughter) where the alpha-galactosidase A defect was associated with a glucose-6-phosphate dehydrogenase (G6PD) deficiency. Mutation analysis revealed for the GLA gene the presence of a new mutation, i.e., a small deletion (c.452delA) on exon 3 and for the G6PD gene the presence of 2 mutations, p.V68M (G6PD Asahi, G6PD A+) and p.N126D (G6PD A+) on exon 3 and exon 4, respectively.

Synergy between the pharmacological chaperone 1-deoxygalactonojirimycin and the human recombinant alpha-galactosidase A in cultured fibroblasts from patients with Fabry disease.

Fabry disease (FD) is an X-linked inherited disease due to alpha-galactosidase A (alpha-Gal A) deficiency and characterized by lysosomal storage of globotriaosylceramide (Gb3) and related neutral glycosphingolipids. Storage of these substrates results in multisystem manifestations, including renal failure, cardiomyopathy, premature myocardial infarctions, stroke, chronic neuronopathic pain, gastrointestinal disturbances, and skin angiokeratoma. Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A (rh-alpha-Gal A) is now available for the treatment of FD and in most patients results in clinical improvement or stabilization. However, ERT efficacy may vary in different tissues and its long-term effects remain to be defined. As a strategy to improve the efficacy of ERT, we tested the combination of rh-alpha-Gal A with the chaperone molecule 1-deoxynojirimycin (DGJ) in cultured FD fibroblasts with negligible residual enzyme activity. Compared to the effects of rh-alpha-Gal A alone, co-administration of DGJ and rh-alpha-Gal A resulted in better correction (4.8 to 16.9-fold) of intracellular alpha-Gal A activity, and increased amounts of the enzyme within the lysosomal compartment. The clearance of lyso-Gb3, one of the substrates stored in FD and a potent inhibitor of alpha-Gal A, was also significantly improved with the co-administration of DGJ and rh-alpha-Gal A. This study provides additional evidence for a synergistic effect between ERT and pharmacological chaperone therapy and supports the idea that the efficacy of combination protocols may be superior to ERT alone.

Nephrotic syndrome and autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the development and growth of cysts in the kidneys and other organs. In ADPKD patients, nephrotic range proteinuria is unusual and needs to be investigated further to exclude coexisting glomerular disease. Among the anecdotal case reports of ADPKD associated with nephrotic syndrome, focal segmental glomerulosclerosis occurs most frequently. METHODS: We report the case of a 26-year-old male with ADPKD and concomitant nephrotic syndrome, in which an ultrasound (US)-guided renal biopsy showed a mesangioproliferative glomerulonephritis. We treated the patient with prednisone 1 mg/kg/day, because of the failure of treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker association. RESULTS: After 6 months of steroid treatment, we observed a stability of his GFR and a reduction of proteinuria. CONCLUSION: This case report and other cases of the literature underline the importance of a renal biopsy in patients with ADPKD and nephrotic syndrome in order to make an accurate diagnosis and an appropriate treatment/prevention of renal function deterioration.

Corticosteroids in patients with IgA nephropathy and severe chronic renal damage.

Little is known about the utility of treating patients with advanced IgA nephropathy (IgAN). From 2001 to 2005, four patients came to our observation because of serum creatinine higher than 3 mg/dL, proteinuria ranging from 1.8 to 5.1 g/day, and a histological picture of diffuse sclerotic lesions. A corticosteroid course of 12 months was given. Patients were observed for a mean follow up of 84 months. At the end of the steroid course, proteinuria lowered quickly below 1 g/day in two patients, whereas the other two experienced a slower and less persistent decrease of proteinuria. Despite similar lesion severity at renal biopsy, renal function stabilized only in these two ones. In conclusion, these preliminary observations suggest a possible efficacy of corticosteroids in slowing down the progression of renal disease and in postponing the need of dialysis in IgAN patients with stage IV CKD and severe chronic histological lesions.

[The ambiguous concept of predialysis: proposal for a model]. / L'ambiguita' del concetto di predialisi: proposta di un modello.

In 2009, 90% of nephrology centers in Lombardy declared to have a ''predialysis'' outpatient department, without, however, specifying its meaning. Research carried out in 2008 among nephrology centers in Piemonte showed how ambiguous this term was. According to the 2007 EDTA-ERA Registry, about 68% of European nephrology centers stated that they had an outpatient department for stage 4-5 CKD patients, but no information was available about the role of patients in the choice of dialysis. It is known that when the predialysis phase is poorly managed, the patient's rehabilitation will be more difficult. Dissatisfaction with dialysis often leads to withdrawal from dialysis, as several registries have shown. For this reason, we created a predialysis course at our center, involving a nephrologist, a nurse, and a dietician. The nephrologist helps the patient choose the most suitable therapeutic strategy, which means that doctor and patient share the responsibility for the treatment choice. The offered options are hemodialysis, peritoneal dialysis, preemptive kidney transplant, and a conservative dietary-pharmacological program. The nurse plans at least 4 meetings: 1) to talk with the patient in order to get to know him or her and his/her family; 2) to provide information about the dialysis procedure and establish the patient's preferences; 3) to clear any doubts about the treatment and deliver a booklet with information about the chosen dialysis procedure; 4) to explain the chosen dialysis procedure; 5) to meet the patient after their preparation for dialysis (vascular access or peritoneal catheter). The dietician manages the dietary programs both for patients who are close to starting dialysis and those on a longlasting conservative program. The predialysis course includes a meeting among all those involved with the patient (nephrologists, nurses, dieticians) to exchange information with the purpose of shared evaluation and decision-making.