Does Renal Denervation a Reasonable Treatment Option in Hemodialysis-Dependent Patient with Resistant Hypertension? A Narrative Review.

PURPOSE OF REVIEW: This narrative review aims to assess the pathophysiology, diagnosis, and treatment of resistant hypertension (RH) in end-stage kidney disease (ESKD) patients on dialysis, with a specific focus on the effect of renal denervation (RDN) on short-term and long-term blood pressure (BP) control. Additionally, we share our experience with the use of RDN in an amyloidotic patient undergoing hemodialysis with RH. RECENT FINDINGS: High BP, an important modifiable cardiovascular risk factor, is often observed in patients in ESKD, despite the administration of multiple antihypertensive medications. However, in clinical practice, it remains challenging to identify RH patients on dialysis treatment because of the absence of specific definition for RH in this context. Moreover, the use of invasive approaches, such as RDN, to treat RH is limited by the exclusion of patients with reduced renal function (eGFR < 45 mL/min/1.73 m3) in the clinical trials. Nevertheless, recent studies have reported encouraging results regarding the effectiveness of RDN in stage 3 and 4 chronic kidney disease (CKD) and ESKD patients on dialysis, with reductions in BP of nearly up to 10 mmhg. Although multiple underlying pathophysiological mechanisms contribute to RH, the overactivation of the sympathetic nervous system in ESKD patients on dialysis plays a crucial role. The diagnosis of RH requires both confirmation of adherence to antihypertensive therapy and the presence of uncontrolled BP values by ambulatory BP monitoring or home BP monitoring. Treatment involves a combination of nonpharmacological approaches (such as dry weight reduction, sodium restriction, dialysate sodium concentration reduction, and exercise) and pharmacological treatments. A promising approach for managing of RH is based on catheter-based RDN, through radiofrequency, ultrasound, or alcohol infusion, directly targeting on sympathetic overactivity.

Vitamin D in kidney transplant recipients
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Kidney transplant recipients (KTRs) are susceptible to low levels of vitamin D, which may be responsible for mineral and bone metabolism disorders and play some role in the occurrence of cardiovascular, metabolic, immunologic, neoplastic, and infectious complications after kidney transplant. Kidney Disease Improving Global Outcomes (KDIGO) guidelines of the year 2017 recommended vitamin D supplementation in the first 12 months after transplant using the same treatment strategies for the general population. However, no recommendations are provided after the first 12 months due to a lack of sufficient data. This review analyses some studies that assessed the vitamin D status of KTRs and the effects of nutritional and active vitamin D supplementation on bone mineral density, cardiovascular disease, proteinuria, and graft function in KTRs.

Contrast-enhanced ultrasound (CEUS) in nephrology: Has the time come for its widespread use?

Grey-scale ultrasound has an important diagnostic role in nephrology. The absence of ionizing radiations and nephrotoxicity, rapidity of execution, excellent repeatability, the possibility to perform the test at the patient's bed and the low cost represent important advantages of this technique. Paired with real-time sonography and colour-power-Doppler contrast-enhanced ultrasound (CEUS) reduces the diagnostic gap with computed tomography (CT) and magnetic resonance (MR) and represents a major step in the evolution of clinical ultrasound. Although there are several situations in which contrast-enhanced CT and MR are indicated (i.e. evaluation of cystic or ischemic lesions, traumatisms and ablative therapies of the native and transplanted kidney), the use of CT contrast media presents a high risk of contrast-induced nephropathy (i.e. in elderly people, subjects with comorbidities and those with renal dysfunction), while gadolinium-based RM contrast agents are contraindicated for the risk of nephrogenic systemic fibrosis (i.e. in patients with severe renal dysfunction). In these situations, CEUS may be a viable alternative, however, as any technique associated with the infusion of pharmacological substances, the potential advantages and risks of CEUS should be critically evaluated. In this regard, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) has published the guidelines for the use of CEUS for the kidney imaging and the International Contrast Ultrasound Society (ICUS) has been recently founded. The aim of this review is to offer an updated overview of the potential applications of CEUS in nephrology, reporting some indications and possible risks associated to its use.

Practical recommendations for performing ultrasound scanning in the urological and andrological fields.

AIM: US scanning has been defined as the urologist's stethoscope. These recommendations have been drawn up with the aim of ensuring minimum standards of excellence for ultrasound imaging in urological and andrological practice. A series of essential recommendations are made, to be followed during ultrasound investigations in kidney, prostate, bladder, scrotal and penile diseases. METHODS: Members of the Imaging Working Group of the Italian Society of Urology (SIU) in collaboration with the Italian Society of Ultrasound in Urology, Andrology and Nephrology (SIEUN) identified expert Urologists, Andrologists, Nephrologists and Radiologists. The recommendations are based on review of the literature, previously published recommendations, books and the opinions of the experts. The final document was reviewed by national experts, including members of the Italian Society of Radiology. RESULTS: Recommendations are listed in 5 chapters, focused on: kidney, bladder, prostate and seminal vesicles, scrotum and testis, penis, including penile echo-doppler. In each chapter clear definitions are made of: indications, technological standards of the devices, the method of performance of the investigation. The findings to be reported are described and discussed, and examples of final reports for each organ are included. In the tables, the ultrasound features of the principal male uro-genital diseases are summarized. Diagnostic accuracy and second level investigations are considered. CONCLUSIONS: Ultrasound is an integral part of the diagnosis and follow-up of diseases of the urinary system and male genitals in patients of all ages, in both the hospital and outpatient setting. These recommendations are dedicated to enhancing communication and evidence-based medicine in an inter- and multi-disciplinary approach. The ability to perform and interpret ultrasound imaging correctly has become an integral part of clinical practice in uro-andrology, but intra and inter-observer variability is a well known limitation. These recommendations will help to improve reliability and reproducibility in uro-andrological ultrasound scanning.

The Impact of Cholecaciferol Supplementation on Bone Mineral Density in Long-Term Kidney Transplant Recipients.

Although reduced bone mineral density (BMD) is associated with a higher risk of fractures, morbidity, and mortality in kidney transplant patients (KTRs), there is no consensus on optimal treatment for the alterations of BMD in this population. This study aims at assessing the effect of cholecalciferol supplementation on BMD over a follow-up period of 2 years in a cohort of long-term KTRs. Patients with age ≥ 18 years were included and divided into two subgroups based on treatment with bisphosphonate and/or calcimimetics and/or active vitamin D sterols (KTRs-treated) or never treated with the above medications (KTRs-free). BMD was evaluated at lumbar vertebral bodies (LV) and right femoral neck (FN) with standard DEXA at the beginning and end of the study. According to World Health Organization (WHO) criteria, results were expressed as T-score and Z-score. Osteoporosis and osteopenia were defined as T score ≤ -2.5 SD and T score < -1 and >-2.5 SD, respectively. Cholecalciferol was supplemented at a dose of 25,000 IU/week over 12 weeks followed by 1500 IU/day. KTRs-free (n. 69) and KTRs-treated (n. 49) consecutive outpatients entered the study. KTRs-free were younger (p < 0.05), with a lower prevalence of diabetes (p < 0.05) and of osteopenia at FN (46.3 % vs. 61.2 %) compared to KTRs-treated. At the entry none of the study subjects had a sufficient level of cholecalciferol; Z-score and T-score at LV and FN were not different between groups. At the end of the study period, serum cholecalciferol concentration was significantly increased in both groups (p < 0.001); the KTRs-free group presented an improvement in both T-score and Z-score at LV (p < 0.05) as well as a lower prevalence of osteoporotic cases (21.7% vs. 15.9%); in contrast, no changes were recorded in KTR-treated individuals. In conclusion, supplementation with cholecalciferol ameliorated Z-score and T-score at LV in long-term KTRs who had been never treated with active or inactive vitamin D sterols, bisphosphonates, and calcimimetics. Future endeavours are needed to confirm these preliminary findings.

Refractory hypertension and rapidly progressive renal failure due to bilateral renal artery stenosis: case report.

INTRODUCTION: We report a case of refractory hypertension and acute renal failure with mild proteinuria due to an unreported bilateral Renal Artery Stenosis, who underwent renal biopsy in the suspicion of rapidly progressive glomerulonephritis. CASE PRESENTATION: A 51-year-old Caucasian male was admitted with refractory hypertension of recent onset and acute renal failure. Duplex Doppler Ultrasonography was performed and provided images highly suggestive for bilateral renal artery stenosis. The patient was referred to the department of interventional radiology, where bilateral selective renal angiography and percutaneous endovascular angioplasty and stenting were performed successfully. CONCLUSION: Duplex Doppler Ultrasonography is thus suggested in patients presenting with refractory hypertension and acute renal failure, especially if atherosclerotic disease and clinical clues of RAS are present. Renal revascularisation with bilateral angioplasty and stenting may play a key role in the treatment of bilateral Renal Artery Stenosis, especially in patients unable to maintain renal function as systemic blood pressure is lowered.

Indication to renal biopsy in DM2 patients: potential role of intrarenal resistive index.

Diagnosis of diabetic nephropathy is generally based, rather than on histological confirmation, on clinical criteria (long history of diabetes, presence of proteinuria, diabetic retinopathy or peripheral neuropathy). This clinical approach has perhaps limited utility in DM2 patients, because only 50% of them show microvascular complications in presence of nephropathy. Eco-colour-Doppler sampling of interlobular renal arteries and determination of their resistance indices (RI), was proposed in the differential diagnosis of numerous nephropathies. Aim of this study was to evaluate whether RI can be useful in discerning non-diabetic renal disease (NDRD), in order to better define indications to perform renal biopsy among proteinuric DM2 patients. All patients were submitted to: echo-colour-Doppler study of renal vessels; systematic screening for diabetic retinopathy; needle renal biopsy. RI resulted to be significantly higher in diabetic glomerulosclerosis (GSD) group as compared with NDRD group, while no significant difference was found with respect to NDRDs overlapping GSD (overlapping group). The last one showed however median RI significantly higher than isolated NDRD group. Normalized chi square Pearson for the hypothesis that RI can predict GSD resulted 0.73, while it resulted 0.43 for the hypothesis that diabetic retinopathy can predict GSD. Echo-colour-Doppler can significantly contribute, more than the other parameters proposed (nephritic or nephrotic syndrome, hematuria, diabetic retinopathy), to the identification of underlying nephropathy in DM2 subjects. In the light of our experience, it seems that the detection of RI values > 0.72 suggests the diagnosis of GSD or mixed forms, reducing the indications to renal biopsy only in presence of values < 0.72.

[Ultrasonography in the hyperhydrated patient]. / La semeiotica ecografica nel paziente iperidratato.

The achievement of a normal hydration state is one of the major targets of hemodialysis. It is based on the estimation of ''dry weight'', which corresponds to the normal body fluid content. Even though the concept of dry weight in hemodialysis patients is clinically undisputed, it is not always easy to achieve in this population. Assessment of the hydration state by clinical examination is imprecise and often unreliable. Measurement of the inferior vena cava (IVC) diameter has been shown to reflect individual fluid status. The relationship between the variation of the IVC diameter before and after the hemodialysis session and weight loss has been investigated. Measurement of the IVC diameter by ultrasound is considered a valid measure of the hydration state and can be routinely used in hemodialysis patients. Moreover, a relationship between IVC diameter, respiratory activity and the hydration state, evaluated by considering both plasma volume and central venous pressure, has been demonstrated. In conclusion, assessment of the hydration state based on blood pressure and central venous pressure can be considered reliable only in patients without signs of heart failure.

[Color-Doppler imaging and arteriovenous fistula: preoperative evaluation and surveillance]. / Eco-color-Doppler e fistola artero-venosa: utilizzo pre e post-chirurgico.

The native arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis because of the lower incidence of complications and longer survival in comparison to grafts and central venous catheters. The use of color-Doppler sonography in the surgery of vascular accesses has increased the number of patients that are eligible for AVF as it allows to optimize the search for vessels suitable for surgical intervention (preoperative vascular mapping). Furthermore, color-Doppler imaging (CDI) has improved the survival of native AVF by increasing the early diagnosis of complications (postoperative surveillance). CDI is the only imaging technique able to provide both morphological and functional information about native vascular access and it is the only tool directly available to the nephrologist. This aspect is undoubtedly an additional value. Here we present a survey of the applications of CDI in the surgery and followup of AVF, with particular reference to preoperative mapping, AVF maturation and surveillance.

[Vascular calcifications in chronic kidney disease]. / Le calcificazioni vascolari nella malattia renale cronica.

Vascular calcifications are associated with increased cardiovascular morbidity and mortality. Their prevalence is higher in patients with chronic kidney disease than in the general population and they are linked not only to classical risk factors such as hypertension, diabetes, dyslipidemia and smoking but also to derangements in mineral metabolism and to chronic inflammation. The development of vascular calcifications is an active phenomenon that is linked to an imbalance between promoting and inhibitory factors. They affect also young patients on dialysis and it is therefore necessary to recognize them at an early stage. The distinction between intima and media calcification can be important for a different therapeutic approach. There are a number of devices for the identification of vascular calcifications, including x-ray imaging, ultrasonography and computerized technologies. The purpose of this paper is to show the advantages and disadvantages of ultrasonography in comparison to other tools for the diagnosis of vascular calcifications.

[Bone ultrasonography in kidney disease: applications and limitations]. / L'ultrasonografia ossea in nefrologia: applicazioni e limiti.

Quantitative ultrasound (QUS) of the bone is a technique that is generating great interest among bone structure researchers because of its intrinsic features. Its safety and low cost make it an ideal technique for repeated measurements over time such as in chronic disease or when it is necessary to monitor the effects of prescribed therapies. The method was developed for the study of osteoporosis and the sites of measurement are all peripheral, including the distal diaphyses and metaphyses of the phalanges, calcaneus, radius and tibia. QUS parameters, however, cannot be used directly for the diagnosis of osteoporosis according to the WHO criteria, although many authors have shown that ultrasound parameters, particularly those of calcaneal QUS, can predict the risk of osteoporotic fractures independently of MBD. Very promising results with the use of QUS have been obtained in corticosteroid-induced osteoporosis, rheumatoid arthritis, Cushing's syndrome, cystic fibrosis, osteomalacia, thalassemia and osteopenia related to parenteral nutrition. QUS can also monitor the effectiveness of therapy in various pathological conditions. In nephrology the combined use of phalangeal QUS and biochemical markers of bone turnover allows adequate follow-up of patients on dialysis and renal transplant recipients with alterations or disorders of the bone.

[Use of ECG-EC in the positioning of central venous catheters]. / Elettrocardiografia endocavitaria nel posizionamento dei cateteri venosi centrali.

Central venous catheters (CVC) are widely used in clinical practice for the administration of chemotherapy, parental nutrition, hemodynamic monitoring, and hemodialysis. International guidelines have defined the right internal jugular vein as the preferred site of CVC insertion and underline that accurate positioning of the catheter tip is essential to maximize the blood flow and reduce long-term complications. Endocavitary electrocardiography (EC-ECG) improves the accuracy of catheter tip positioning without increasing the placement time by the recognition of typical P wave patterns during catheter insertion:the normally shaped P wave identifies the mid to upper superior vena cava, the widest P wave may be used to place the CVC tip at the superior vena cava-right atrium junction, and biphasic P waves identify the location of the right atrium. Because of its simplicity and safety, EC-ECG should always be considered during CVC placement, especially if other means of verifying correct CVC insertion are not available.

[The future of the ultrasonography techniques in nephrology]. / Il futuro delle tecniche ultrasonografiche in nefrologia.

Thanks to the wide geographical diffusion, low cost and lack of ionizing radiation, ultrasound is now the most widely used imaging technique in clinical practice, second only to chest radiography. Recent technological innovations and introduction of ultrasound contrast agents, further expanded the fields of application of ultrasound, guarantying for the future to this technique an important role in imaging of the urinary tract. The nephrologist must be able to exploit the potential offered by technological innovations in ultrasound imaging for the study of the kidney. The proper management of equipment, in fact, allows to obtain ultrasound images in gray scale of the highest quality, to optimize the diagnostic accuracy of Doppler techniques and take full advantage of the tools offered by means of ultrasound contrast agents.

[Microbubbles: current state and future prospects]. / Le microbolle: attualita' e prospettive future.

Contrast-enhanced ultrasound (CEUS) represents one of the most interesting applications of traditional medical sonography. Ultrasound contrast agents are classified into first- and second-generation agents depending on the gas (nitrogen, perfluorocarbon or sulfur hexafluoride) in the microbubbles. Both generations are characterized by an excellent safety profile, with low hepatic and renal toxicity and rare central nervous system reactions. The respiratory and hepatic elimination of the gases explains the low nephrotoxicity. CEUS has been successfully employed in drug and gene delivery. Indeed, new molecules such as liposomes, micelles and perfluorocarbon nanoparticles have been recently proposed as ultrasound contrast agents. Possible future applications of liposomes are the treatment of hypertension complications (given the possibility to fill them with nitric oxide), the treatment of cerebral disease with xenon, and the treatment of breast and liver cancer with doxorubicin. Micelles have been demonstrated to be effective in cancer treatment as well. Finally, perfluorocarbon nanoparticles can be used in oncological settings and in pancreatic islet transplantation in patients with type I diabetes.

[Contrast enhanced ultrasound in renal diseases]. / L'imaging ecocontrastografico nella patologia renale.

Contrast-enhanced ultrasound (CEUS) is one of the most interesting and promising clinical applications of imaging and ultrasound. Thanks to the absence of ionizing radiation, the lack of nephrotoxicity and low cost it has the potential to become a reference in imaging of the kidney. This review, besides providing a brief description of the proper methodology, presents possible applications of CEUS in nephrology and urology, including renal ischemia, the differential diagnosis of cystic and solid lesions, follow-up of ablative therapies, kidney trauma, kidney transplant, inflammatory diseases, ischemic nephropathy and vesicoureteral reflux.

[Ultrasound assessment in renal infections]. / L'ecografia nelle infezioni del rene.

Urinary tract infections (UTIs) are a common clinical problem, especially among women. Ultrasound assessment is indicated in case of complicated UTIs, in particular in children, pregnant women and patients with chronic kidney disease. Even though B-mode imaging alone is rarely diagnostic in case of particular kidney infections such as focal and multifocal acute pyelonephritis, Doppler and power-Doppler (PD) techniques are able to increase its sensitivity. Contrast-enhanced ultrasound (CEUS) further improves the signal-to-noise ratio, thus increasing the diagnostic accuracy of ultrasound in case of renal infectious disease. Recent studies performed on kidney transplant recipients have indeed demonstrated the high sensitivity and specificity of CEUS in diagnosing acute pyelonephritis. Moreover, ultrasonography is a useful diagnostic tool in case of kidney abscesses, emphysematous pyelonephritis, early phases of pyonephrosis, and in the evaluation and monitoring of echinococcal cysts. Ultrasound imaging is less specific in diagnosing xanthogranulomatous pyelonephritis, malacoplakia and renal tuberculosis. Finally, several authors recommend routine ultrasound assessment in HIV patients, given the high incidence of renal complications in this population of patients.

[Parenchymal complications of the transplanted kidney: the role of color-Doppler imaging]. / Le complicanze parenchimali del rene trapiantato: il ruolo dell'eco-color-Doppler.

Kidney transplantation is the treatment of choice for end-stage renal disease, given the better quality of life of transplanted patients when compared to patients on maintenance dialysis. In spite of surgical improvements and new immunosuppressive regimens, part of the transplanted grafts still develop chronic dysfunction. Ultrasonography, both in B-mode and with Doppler ultrasound, is an important diagnostic tool in case of clinical conditions which might impair kidney function. Even though ultrasonography is considered fundamental in the diagnosis of vascular and surgical complications of the transplanted kidney, its role is not fully understood in case of parenchymal complications of the graft. The specificity of Doppler ultrasound is low both in case of acute complications such as acute tubular necrosis, drug toxicity and acute rejection, and in case of chronic conditions such as chronic allograft nephropathy. Single determinations of resistance indices present low diagnostic accuracy, which is higher in case of successive measurements performed during the follow-up of the graft. Modern techniques including tissue pulsatility index, maximal fractional area and contrast-enhanced ultrasound increase the diagnostic power of ultrasonography in case of parenchymal complications of the transplanted kidney.

[Vascular complications following kidney transplant: the role of color-Doppler imaging]. / Le complicanze vascolari del rene trapiantato: il ruolo dell'eco-color-Doppler.

The progressive decline in the incidence of graft rejection has made urological, surgical, parenchymal and vascular complications of kidney transplant more frequent. The latter, although accounting for only 5-10% of all post-transplant complications, are a frequent cause of graft loss. Ultrasonography, both in B-mode and with Doppler ultrasound, is an important diagnostic tool in case of clinical conditions which might impair kidney function. Even though ultrasonography is considered fundamental in the diagnosis of parenchymal and surgical complications of the transplanted kidney, its role is not fully understood in case of vascular complications of the graft. The specificity of Doppler ultrasound is very important in case of stenosis of the transplanted renal artery, pseudoaneurysms, arteriovenous fistulas, and thrombosis with complete or partial artery or vein occlusion. Doppler and color determinations present high diagnostic accuracy, which is higher in case of successive measurements performed during the follow-up of the graft. Modern techniques including contrast-enhanced ultrasound increase the diagnostic power of ultrasonography in case of vascular complications of the transplanted kidney, planted kidney.

[Echocardiography in nephrology]. / L'ecocardiografia in nefrologia.

Cardiovascular disease is the main cause of mordibity and mortality in patients with chronic kidney disease (CKD) affected by a series of risk factors (hypertension, anemia, left ventricular hypertrophy, cardiac failure and dyslipidemia). The combined presence of these factors raises the cardiovascular risk in CKD patients considerably compared with that of the general population. Nephrologists can play a role in preventing and treating these risk factors and thereby delaying the development of CKD. In preventing CKD, nephrologists who practice ultrasound techniques should have basic know how of echocardiography so that they can screen CKD patients for early referral to a cardiologist. Echocardiography is a noninvasive ultrasound technique that requires adequately trained doctors to perform it. Nephrologists who practice it need to obtain good training and postgraduate certification of competence in echocardiography. These nephrologists should team up with cardiologists rather than replace them, and at the same time be aware that they possess the basic knowledge to manage cardiovascular disease in CKD patients.