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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., (© 2023. The Author(s).)

Home dialysis is a primary objective of Italian Ministry of Health. As stated in the National Chronicity Plan and the Address Document for Chronic Renal Disease, it is mostly home hemodialysis and peritoneal dialysis to be carried out in the patient's home. Home hemodialysis has already been used in the past and today has found new technologies and new applications. The patient's autonomy and the need for a caregiver during the sessions are still the main limiting factors. In this multicenter observational study, 7 patients were enrolled for 24 months. They underwent six weekly hemodialysis sessions of 180' each; periodic medical examinations and blood tests were performed (3, 6, 12, 18 and 24 months). After 3-6 months of home hemodialysis there was already an improvement in the control of calcium-phosphorus metabolism (improvement in phosphorus values, (p <0.01), a reduction in parathyroid hormone (p <0.01)); in the number of phosphorus binders used (p <0.02); in blood pressure control (with a reduction in the number of hypotensive drugs p <0.02). Home hemodialysis, although applicable to a small percentage of patients (10-15%), has improved blood pressure control, calcium-phosphorus metabolism and anemia, reducing the need for rhEPO., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Protein Energy Wasting (PEW) in hemodialysis (HD) patients is a multifactorial condition due to specific pathology-related pathogenetic mechanisms, leading to loss of skeletal muscle mass in HD patients. Computed Tomography and Magnetic Resonance Imaging still represent the gold standard techniques for body composition assessment. However, their widespread application in clinical practice is difficult and body composition evaluation in HD patients is mainly based on conventional anthropometric nutritional indexes and bioelectrical impedance vector analysis (BIVA). Little data is currently available on ultrasound (US)-based measurements of muscle mass and fat tissue in this clinical setting. The purpose of our study is to ascertain: (1) if there are differences between quadriceps rectus femoris muscle (QRFM) thickness and abdominal/thigh subcutaneous fat tissue (SFT) measured by US between HD patients and healthy subjects; (2) if there is any correlation between QRFM and abdominal/thigh SFT thickness by US, and BIVA/conventional nutritional indexes in HD patients. We enrolled 65 consecutive HD patients and 33 healthy subjects. Demographic and laboratory were collected. The malnutrition inflammation score (MIS) was calculated. Using B-mode US system, the QRFM and SFT thicknesses were measured at the level of three landmarks in both thighs (superior anterior iliac spine, upper pole of the patella, the midpoint of the tract included between the previous points). SFT was also measured at the level of the periumbilical point. The mono frequency (50 KHz) BIVA was conducted using bioelectrical measurements (Rz, resistance; Xc, reactance; adjusted for height, Rz/H and Xc/H; PA, phase angle). 58.5% were men and the mean age was 69 (SD 13.7) years. QRFM and thigh SFT thicknesses were reduced in HD patients as compared to healthy subjects ( p < 0.01). Similarly, also BIVA parameters, expression of lean body mass, were lower ( p < 0.001), except for Rz and Rz/H in HD patients. The average QRFM thickness of both thighs at top, mid, lower landmarks were positively correlated with PA and body cell mass (BCM) by BIVA, while negatively correlated with Rz/H ( p < 0.05). Abdominal SFT was positively correlated with PA, BCM and basal metabolic rate (BMR) ( p < 0.05). Our study shows that ultrasound QRFM and thigh SFT thicknesses were reduced in HD patients and that muscle ultrasound measurements were significantly correlated with BIVA parameters., Competing Interests: The authors declare that they have no conflict of interest.

In recent years imaging techniques that use radionuclides have become more and more clinically relevant as they can provide functional information for specific anatomical districts. This has also involved nephrology, where radionuclides are used to study patients with different degrees of renal function failure up to terminal uremia. Although chronic kidney disease, and dialysis in particular, may affect the distribution and the elimination of radiopharmaceuticals, to date there are no consistent data on the risks associated with their use in this clinical context. In addition to the lack of data on the safety of radio-exposure in dialysis patients, there is also a shortage of information concerning the risk for healthcare staff involved in conducting the dialysis sessions performed after a nuclear test. This study, performed on 29 uremic patients who underwent hemodialysis immediately after a scintigraphic examination, assessed the extent of radio-contamination of the staff and of hemodialysis devices such as monitor, kits and dialysate. The data collected has been used to quantify the radiological risk in dialysis after the exposure to the most common radionuclides., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Progressive and generalized loss of muscle mass (muscle wasting) is a frequent complication in dialysis patients. Common uremic signs and symptoms such as insulin-resistance, increase in glucocorticoid activity, metabolic acidosis, malnutrition, inflammation and dialysis per se contribute to muscle wasting by modulating proteolytic intracellular mechanisms (ubiquitin-proteasome system, activation of caspase-3 and IGF-1/PI3K/Akt pathway). Since muscle wasting is associated with an increase in mortality, bone fractures and worsening in life quality, a prompt and personalised diagnostic and therapeutic approach seems to be essential in dialysis patients. At present, nuclear magnetic resonance (NMR), computed tomography (CT), dual-energy x-ray absorptiometry (DXA), impedance analysis, bioelectric impedance analysis (BIA) and anthropometric measurements are the main tools used to assess skeletal muscle mass. Aerobic and anaerobic training programmes and treatment of uremic complications reduce muscle wasting and increase muscle strength in uremic patients. The present review analyses the most recent data about the physiopathology, diagnosis, therapy and future perspectives of treatment of muscle wasting in dialysis patients.

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

Variations in the course of the blood vessels are often incidental findings during clinical examination. Persistent left superior vena cava (PLSVC) is an uncommon anomaly, estimated to be present in about 0.3-0.5% of healthy individuals and in about 3-10% of patients with congenital heart disease. It results from the failure of the left anterior cardinal vein to degenerate during embryological development. Serious complications such as shock, angina and cardiac arrest have been described during catheterization in adults with a PLSVC. Since it frequently goes undiagnosed because of lack of symptoms when not accompanied by other anomalies, variations of the superior vena cava should be considered, especially when central venous catheterization via the subclavian or internal jugular vein is difficult. The embryological development, diagnosis, and clinical implications of a PLSVC are therefore reviewed in this article.

The concept of regeneration of dialysis fluids and of ultrafiltrate in particular has been recently revisited. Hemodiafiltration with online regeneration of the ultrafiltrate allows the concomitant infusion of sodium, calcium, and bicarbonate. Here, we studied the adsorptive characteristics of an integrated two-step sorbent system relative to different solutes present in the ultrafiltrate: sodium, calcium, phosphate, bicarbonate, uric acid, creatinine, and beta2-microglobulin. In vitro studies were performed in order to differentiate the relative roles for each sorbent (mineral-activated charcoal or hydrophobic resin) in adsorbing a given solute. Ex vivo studies were performed in order to evaluate the presence of cytokines (interleukin-1 beta and tumor necrosis factor-alpha), of cytokine (interleukin-1 beta and tumor necrosis factor-alpha)-inducing activities, and of the cytokine release in response to exogenous bacterial lipopolysaccharide by normal whole blood incubated with ultrafiltrate samples obtained at 15, 120, and 240 minutes after the start of treatment. The results of the present studies show the presence of immunomodulatory substances in the ultrafiltrate and the significant (P < 0.01) increase in the lipopolysaccharide-induced release of both interleukin-1 beta and tumor necrosis factor-alpha. The biological relevance of the ultrafiltrate and the possible relevance of the online, endogenous reinfusion are discussed.

Some degrees of protein deficiency, suggestive of abnormal protein metabolism, are a well-known feature of chronic renal failure (CRF). Serum albumin concentration, an index of malnutrition and deranged protein metabolism, is frequently decreased relatively early in CRF, even in absence of heavy proteinuria: a more subtle but characteristic abnormality is found in the plasma profile of amino acids. In addition, there is an accumulation in the plasma and tissues of many products of protein metabolism; some of these have been considered as uremic toxins, while others are largely undefined. The origin of abnormalities in protein metabolism are multifactorial. The defect are caused at least partly by dietary deficiency, as well as by the inability of the failing kidney to excrete normal end products of nitrogen and protein metabolism and by the effect of altered uremic milieu on overall metabolism.

To assess the effect of recombinant human growth hormone (rhGH) on muscle protein metabolism in uremic patients with malnutrition, forearm [3H]phenylalanine kinetics were evaluated in six chronically wasted (body weight 79% of ideal weight) hemodialysis (HD) patients in a self-controlled, crossover study. Forearm protein dynamics were evaluated before, after a 6-wk course of rhGH (5 mg thrice weekly) and after a 6-wk washout period. After rhGH: (a) forearm phenylalanine net balance--the difference between phenylalanine incorporation into and phenylalanine release from muscle proteins--decreased by 46% (-8+/-2 vs. -15+/-2 nmol/min x 100 ml at the baseline and -11+/-2 after washout, P < 0.02); (b) phenylalanine rate of disposal, an index of protein synthesis, increased by 25% (25+/-5 vs. 20+/-5 at the baseline and 20+/-4 after washout, P < 0.03); (c) phenylalanine rate of appearance, an index of protein degradation, was unchanged (33+/-5 vs. 35+/-5 at the baseline and 31+/-4 after washout); (d) forearm potassium release declined (0.24+/-0.13 vs. 0.60+/-0.15 microeq/min at the baseline, and 0.42+/-0.20 microeq/min after washout P < 0.03); (e) changes in the insulin-like growth factor binding protein (IGFBP)-1 levels and insulin-like growth factor-I (IGF-I)/IGFBP-3 ratios accounted for 15.1% and 47.1% of the percent variations in forearm net phenylalanine balance, respectively. Together, these two factors accounted for 62.2% of variations in forearm net phenylalanine balance during and after rhGH administration. These data indicate: (a) that rhGH administration in malnourished hemodialysis patients is followed by an increase in muscle protein synthesis and by a decrease in the negative muscle protein balance observed in the postabsorptive state; and (b) that the reduction in net protein catabolism obtained with rhGH can be accounted for by the associated changes in circulating free, but not total, IGF-I levels.

Renal failure (RF) is a common accompaniment of multiple myeloma and is identified in over half of patients at presentation. RF is usually related to the presence of Bence-Jones protein (immunoglobulin light chain) which damages all the compartments of the kidney: glomerule, tubulo-interstitium and vasculature. The most common renal lesion is cast nephropathy, named "myeloma kidney": Cast are produced by two mechanisms: proximal tubule damage and intratubular cast formation. The predominant pathophysiologic mechanism of tubule damage appears to be a precipitation of Bence-Jones protein and Tamm-Horsfall glycoprotein produced by cells of ascending limb of Henle's loop in the tubule lumen. The therapeutic maneuvers to reduce renal damage and preserve renal function are reduction of plasma concentration of light chain with chemotherapy, elimination of factors which favour coprecipitation of Tamm-Horsfall protein with light chain (hypercalcemia, acid urine, radiocontrast material, furosemide, oliguria). At last, colchicine (1.2 mg/day) will also be efficacious in the acute management of patients with cast nephropathy.

Chronic renal failure is characterized by abnormalities in glucose metabolism. In fact there are present a normal fasting plasma glucose level )or mild hyperglycemia) in the presence of hyperinsulinemia, blunted decrease in the plasma glucose concentration in response to exogenous insulin administration, and diminished effect of intravenous insulin on glucose uptake in forearm perfusion studies. The glucose intolerance is not the result of reduced insulin secretion, or circulating insulin antagonists, and does not correlate with the coexisting metabolic acidosis. Glucose intolerance exists because the peripheral insulin-sensitive tissue (muscle, adipose tissue, liver) of the patients with chronic renal failure are insulin resistant. However there are two subgroups of uremic patients with regard to glucose tolerance: about half of uremic patients can augment their insulin secretion sufficiently to maintain normal glucose tolerance despite glucose intolerance. In the other half, insulin secretion following glucose loads is not different from normal values, so that glucose intolerance results. The cause of the peripheral insulin resistance remain unclear. Besides deranged renal function can result in the development of hypoglycemia. The most important predisposing mechanism to hypoglycemia is diminished glucose availability due to substrate limitation; the second important mechanism (alcohol, insulin, propranolol, etc.). Finally, in chronic renal failure persistent hyperinsulinemia can contribute hyperlipemia and to high incidence of cardiovascular disease.

Peripheral tissue metabolism of branched-chain amino acids (BCAA) and branched-chain keto acids (BCKA) in the postabsorptive state was evaluated in 8 patients with chronic renal failure (CRF) and 7 controls by measuring the arterial-deep forearm venous differences for BCAA and BCKA. Arterial whole blood levels of BCAA and BCKA were also measured in an additional 7 patients and 11 controls. In CRF, total BCKA levels are reduced owing to a decrease in ketoisocaproic acid (KICA) and ketoisovaleric acid (KIVA) levels, parallel to changes in BCAA levels, whereas levels of ketomethylvaleric acid (KMVA) are not different from controls. Both in normal conditions and in patients, arterial levels of individual BCAA are directly correlated with arterial levels of the corresponding BCKA. However, in CRF, the ratios of leucine to KICA and of isoleucine to KMVA are increased. A direct correlation between KICA and HCO3- levels is observed. In CRF, the release of leucine and valine as well as of KICA and KMVA from peripheral tissues is reduced, whereas KIVA is neither released nor taken up by the forearm. The lack of KICA release from peripheral tissues likely accounts for its low circulating levels. The depressed peripheral release of leucine associated with the lack of KICA release suggests an increased degradation of leucine which proceeds beyond the transamination step.

The occurrence of malnutrition in patients with chronic renal failure has been well documented, mostly in patients undergoing regular dialysis: these patients often suffer from protein-calorie malnutrition, but more seldom there are disturbances to be due to deficit of 1,25 dihydroxyvitamin D3, folic acid, vitamin B6, iron, zinc and L-carnitine, mostly in patients who do not get adequate supplementation. There are several causes for protein-calorie malnutrition in chronic renal insufficiency. These include uremia per se, altered hormonal milieu, abnormal amino acid metabolism due to uremia or to loss of metabolically active renal tissue. Dialysis treatment improves some of these abnormalities, but introduces others. On the other hand, it is well established that morbidity and mortality in chronic renal failure are influenced by their nutritional status: therefore it is important to know the factors and the mechanisms that cause malnutrition for its prevention, recognition and correction.

Carnitine plays an important role in regulating the flow of energetic substrates and their balance through cellular membranes. Usually in chronic renal failure, increased plasma levels of carnitine are found. In early hemodialysis a slow decrease of the muscle concentrations of carnitine is found, followed by a decrease of plasma concentrations long after substitutive treatment. Several signs and symptoms are attributable to carnitine deficiency. It is reported that these changes regress with suitable supply of intravenous carnitine after dialysis end for 15-30 days, and subsequently with chronic administration in the dialysis fluid.