Role of the CD40-CD40 Ligand Pathway in Cardiovascular Events, Neurological Alterations, and Other Clinical Complications of Chronic Hemodialysis Patients: Protective Role of Adsorptive Membranes.

Despite the recent advances in dialysis technology, mortality rate of chronic uremic patients still remains excessively high: of note, in comparison to age- and sex-matched healthy controls, this frail population shows a higher incidence of infections, cancer, cognitive decline, and, in particular, major adverse cardiovascular events (MACE) that represent nowadays the first cause of mortality. Several traditional and nontraditional factors contribute to this increased risk for MACE and accelerated cellular senescence: among these, inflammation has been shown to play a key role. The costimulatory pathway CD40-CD40 Ligand (CD40L) is harmfully activated during inflammation and uremia-associated clinical complications: in particular, the soluble form of CD40L (sCD40L) can bind to the CD40 receptor triggering a cascade of detrimental pathways in immune and nonimmune cells. In this narrative review, we summarize the current concepts of the biological role of the CD40-CD40L pathway in uremia-associated organ dysfunction, focusing on the above-described main causes of mortality. Moreover, we discuss the interaction of the CD40-CD40L pathway with extracellular vesicles, microparticles recently identified as new uremic toxins. The biological effects of sCD40L in MACE, cognitive decline, infections, and cancer will be also briefly commented. Last, based on recent studies and ongoing clinical trials, we herein describe the modulatory activity of adsorptive dialysis membranes in polymethylmethacrylate on CD40-CD40L detrimental activation.

Online Hemodiafiltration Inhibits Inflammation-Related Endothelial Dysfunction and Vascular Calcification of Uremic Patients Modulating miR-223 Expression in Plasma Extracellular Vesicles.

Decreased inflammation and cardiovascular mortality are evident in patients with end-stage chronic kidney disease treated by online hemodiafiltration. Extracellular vesicles (EV) are mediators of cell-to-cell communication and contain different RNA types. This study investigated whether mixed online hemodiafiltration (mOL-HDF) beneficial effects associate with changes in the RNA content of plasma EV in chronic kidney disease patients. Thirty bicarbonate hemodialysis (BHD) patients were randomized 1:1 to continue BHD or switch to mOL-HDF. Concentration, size, and microRNA content of plasma EV were evaluated for 9 mo; we then studied EV effects on inflammation, angiogenesis, and apoptosis of endothelial cells (HUVEC) and on osteoblast mineralization of vascular smooth muscle cells (VSMC). mOL-HDF treatment reduced different inflammatory markers, including circulating CRP, IL-6, and NGAL. All hemodialysis patients showed higher plasma levels of endothelial-derived EV than healthy subjects, with no significant differences between BHD and mOL-HDF. However, BHD-derived EV had an increased expression of the proatherogenic miR-223 with respect to healthy subjects or mOL-HDF. Compared with EV from healthy subjects, those from hemodialysis patients reduced angiogenesis and increased HUVEC apoptosis and VSMC calcification; however, all these detrimental effects were reduced with mOL-HDF with respect to BHD. Cell transfection with miR-223 mimic or antagomiR proved the role of this microRNA in EV-induced HUVEC and VSMC dysfunction. The switch from BHD to mOL-HDF significantly reduced systemic inflammation and miR-223 expression in plasma EV, thus improving HUVEC angiogenesis and reducing VSMC calcification.

The forearm arteriovenous graft between the brachial artery and the brachial vein as a reliable dialysis vascular access for patients with inadequate superficial veins.

OBJECTIVE: The arteriovenous fistula (AVF) is recommended as the preferred hemodialysis access. However, placing an AVF in all patients may result in poor access outcomes and increased central venous catheter (CVC) use because of increased comorbid conditions, age, and suboptimal vessels. In patients with inadequate superficial veins for AVFs, the use of the brachial veins for creation of forearm arteriovenous grafts (AVGs) has received limited attention. This retrospective study aimed to evaluate outcomes of forearm brachial-brachial AVGs (BB-AVGs) placed in patients with poor superficial veins. METHODS: We identified 111 BB-AVGs created in 111 consecutive patients, using standard-walled polytetrafluoroethylene grafts, between January 2010 and December 2015. After excluding 6 patients (non-dialysis initiation, missing information, and death within 1 month), we included 105 patients from 21 dialysis centers. We analyzed primary failures, time to cannulation, patency, complications, and revisions. Patency rates were calculated by the Kaplan-Meier method. The incidence of complications and revisions was expressed as number of events per person-year. RESULTS: A total of 105 patients (median age, 69 years) were followed up for a median time of 21.2 months (interquartile range, 9.2-36.5 months). Of the patients, 72.4% were on chronic hemodialysis and had previously undergone one or more access procedures. At the time of BB-AVG placement, prior accesses were 39 AVFs, 20 tunneled CVCs, and 17 AVGs. BB-AVG rates of primary failure and revision before cannulation were 7.6% and 5.7%, respectively. BB-AVGs were cannulated after a median time of 3.4 weeks (interquartile range, 2.8-4.1 weeks). Primary patency rates at 12, 24, and 36 months were 49.5%, 29.5%, and 19.5%. Secondary patency rates at 12, 24, and 36 months were 76.3%, 62.7%, and 54.6%. After cannulation, the incidence of complications and revisions was 1.054 and 0.649 per person-year, respectively. Most complications and interventions were due to thrombosis (0.527 per person-year) or stenosis (0.381 per person-year) and related interventions (0.490 per person-year). A minority of patients experienced AVG infections (0.052 per person-year), with only two requiring access removal. CONCLUSIONS: In patients with poor superficial veins, the forearm BB-AVG is a reliable access because of low access-related morbidity and considerable long-term access survival. BB-AVG placement has the advantage of preserving proximal vessels. In these patients, such an approach can delay both rapid exhaustion of vascular sites and early recourse to CVC permanent use.

Improving Erythropoiesis Stimulating Agent Hyporesponsiveness in Hemodialysis Patients: The Role of Hepcidin and Hemodiafiltration Online.

Hyporesponsiveness to erythropoietin stimulating agents (ESAs) is a condition associated with increased mortality. Even after identifying the condition, the causes are difficult to treat and only partially reversible in end-stage renal disease patients. Thus, the role of more recent hemodialysis (HD) techniques in improving such conditions is an emerging issue. However, major randomized clinical trials have not confirmed the results of smaller observational studies in which online hemodiafiltration has shown some efficacy in improving patients' response to ESAs. In our interpretation, these findings are not in contrast, but they can be explained by a better understanding of the interactions between HD and ESAs on iron mobilization, first of all through the role of hepcidin. The kinetics of hepcidin removal through HD combined with the action of selected ESAs may help the clinician in prescribing the best association between HD treatment and ESAs to overcome hyporesponsiveness.

Efficacy of a remote web-based lung ultrasound training for nephrologists and cardiologists: a LUST trial sub-project.

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

Outcomes of Vascular Access Care and Surgery Managed by Interventional Nephrologists: A Twelve-Year Experience.

BACKGROUND: Optimizing vascular access outcomes is still a challenge, since 30-60% of arteriovenous fistulas fail or do not mature and catheters are widely used in contemporary patients. METHODS: This study reports on strategies and outcomes in a single center in which access planning, surgery and maintenance are managed by a team of nephrologists. We retrospectively analyzed 305 fistulas and 61 grafts created in 270 consecutive patients between 2002 and 2013. RESULTS: The percentage of patients receiving a fistula or graft who initiated hemodialysis with a mature access was 68.6%. Among prevalent patients, 71.7% used a fistula, 15.7% a graft and 12.6% a catheter. Rates of primary failure and revision before cannulation were 14.4 and 1.6% for fistulas vs. 4.9 and 3.3% for grafts. After maturation, complications (1.040 vs. 0.188 per patient-year (py)) and interventions (0.743 vs. 0.066 per py) were greater for grafts than for fistulas (p < 0.001). Secondary patency did not significantly differ between grafts and fistulas (median survival 34.8 vs. 57.3 months, p = 0.36), unless primary failures were excluded from Kaplan-Meier analysis (median survival 34.9 vs. 70.9 months, p = 0.03). CONCLUSIONS: High fistula prevalence, low access-related morbidity and catheter dependence were achieved using individualized strategies, including mid-forearm or perforating vein fistula creation and selective graft placement in high risk patients. Direct involvement of nephrologists throughout all steps of access care can improve access outcomes, by promoting a patient-centered approach.

High-volume online haemodiafiltration improves erythropoiesis-stimulating agent (ESA) resistance in comparison with low-flux bicarbonate dialysis: results of the REDERT study.

BACKGROUND: In haemodialysis (HD) patients, anaemia is associated with reduced survival. Despite treatment with erythropoiesis-stimulating agents (ESAs), a large number of patients with chronic kidney disease show resistance to this therapy and require much higher than usual doses of ESAs in order to maintain the recommended haemoglobin (Hb) target, and recent studies suggest that hepcidin (HEP) may mediate the ESA resistance index (ERI). High-volume online haemodiafiltration (HV-OL-HDF) has been shown to improve anaemia and to reduce the need for ESAs in HD patients; this effect is associated with a reduced inflammatory state in these patients. The aim of the REDERT study (role of haemodiafiltration on ERI) was to investigate the effect of different dialysis techniques on ERI and HEP levels in chronic dialysis patients. METHODS: A single cross-over, randomized, multicentre study (A-B or B-A) was designed. Forty stable HD patients from seven different dialysis units (male 65%, mean age 67.6 ± 14.7 years and mean dialytic age 48 ± 10 months) were enrolled. Patients were randomized to the standard bicarbonate dialysis (BHD) with low-flux polysulfone (PS) membrane group or to the HV-OL-HDF group with high-flux PS membranes and exchange volume of >20 L/session. After 6 months, patients were shifted to the other dialytic group for a further 6 months. Clinical data, Hb, ESA doses and iron metabolism were recorded every month. HEP, beta2-microglobulin (b2MG) and C-reactive protein (CRP) were determined every 3 months, and ERI was calculated monthly as the weekly ESA dose per kilogram of body weight divided by Hb level. Data were analysed using paired-samples t-test, Wilcoxon signed-rank test and Spearman's correlation coefficient. RESULTS: Dialysis efficiency for small molecules assessed as Kt/V was significantly increased in HV-OL-HDF from 1.47 ± 0.24 to 1.49 ± 0.16; P < 0.01. A significant reduction of b2MG was obtained in HV-OL-HDF from month 3 whereas CRP values were not significantly changed during the study period either in BHD or HV-OL-HDF.ERI was significantly reduced in HV-OL-HDF at month 3 and 6 (from 9.1 ± 6.4 UI/weekly/Kg/Hb to 6.7 ± 5.3 UI/weekly/Kg/Hb; P < 0.05) due to a higher ESA consumption in BHD in spite of similar Hb levels. HEP levels were reduced in HV-OL-HDF with respect to BHD after 3 and 6 months. Iron consumption was not significantly different during BHD or HV-OL-HDF treatment as well as transferrin, ferritin and TSAT levels. A significant positive linear correlation between HEP and ERI (r(2) = 0.258, P < 0.001) was observed. CONCLUSIONS: In a uraemic patient population with low-grade inflammation treated with HV-OL-HDF, we observed a significant reduction of ERI values as well as HEP levels. The positive correlation between these two parameters supports a role for HEP in the development of ERI in the dialytic population. Moreover, the lower b2MG and the higher Kt/V achieved in HV-OL-HDF confirms the better depurative effect of this technique in comparison with BHD with respect to middle molecules and small-molecular-weight molecules.

Endothelial progenitor cell-derived extracellular vesicles protect from complement-mediated mesangial injury in experimental anti-Thy1.1 glomerulonephritis.

BACKGROUND: Endothelial progenitor cells (EPCs) are known to induce tissue repair by paracrine mechanisms including the release of growth factors and extracellular vesicles (EVs), nanoparticles able to carry proteins and genetic information to target cells. The aim of this study was to evaluate whether EVs derived from EPCs may protect from complement-mediated mesangial injury in experimental anti-Thy1.1 glomerulonephritis. METHODS: EVs were isolated by serial ultracentrifugation from supernatants of cultured human EPCs and characterized for their protein and RNA content. In vivo, EVs were injected i.v. in the experimental rat model of mesangiolytic anti-Thy1.1 glomerulonephritis evaluating renal function, proteinuria, complement activity and histological lesions. In vitro, the biological effects of EPC-derived EVs were studied in cultured rat mesangial cells incubated with anti-Thy1.1 antibody and rat or human serum as complement source. RESULTS: After i.v. injection in Thy1.1-treated rats, EVs localized within injured glomeruli and inhibited mesangial cell activation, leucocyte infiltration and apoptosis, decreased proteinuria, increased serum complement haemolytic activity (CH50) and ameliorated renal function. EV treatment decreased intraglomerular deposition of the membrane attack complex (MAC or C5b-9) and expression of smooth muscle cell actin and preserved the endothelial antigen RECA-1 and the podocyte marker synaptopodin. The protective effect of EVs was significantly reduced by pre-treatment with a high dose of RNase (1 U/mL), suggesting a key role for EV-carried RNAs in these mechanisms. Indeed, EPC-derived EVs contained different mRNAs coding for several anti-apoptotic molecules and for the complement inhibitors Factor H, CD55 and CD59 and the related proteins. The in vitro experiments aimed to investigate the mechanisms of EV protection indicated that EVs transferred to mesangial cell mRNAs coding for Factor H, CD55 and CD59 and inhibited anti-Thy1.1 antibody/complement-induced apoptosis and C5b-9/C3 mesangial cell deposition. CONCLUSIONS: EVs derived from EPCs exert a protective effect in Thy1.1 glomerulonephritis by inhibition of antibody- and complement-mediated injury of mesangial cells.

Anti-inflammatory effect of white wine in CKD patients and healthy volunteers.

BACKGROUND: Mediterranean-style diet has been considered for its important beneficial effects on the progression of CV disease. Wine is an important component of the Mediterranean diet, and moderate wine drinkers have lower mortality rates than nondrinkers and heavy drinkers in epidemiologic studies. The beneficial effects of red wine are thought to be dependent on the polyphenol compounds such as resveratrol that exhibit potent antioxidant activity. However, white wine, although lacking polyphenols, contains simple phenols, such as tyrosol (Tyr) and hydroxytyrosol (OH-Tyr), characteristic also of extra-virgin olive oil, which may share similar antioxidant and inflammatory properties. PATIENTS AND METHODS: The effect of white wine and extra-virgin olive oil on inflammatory markers was evaluated in 10 healthy volunteers and in 10 patients with CKD (chronic kidney disease) K-DOQI stage III-IV in a prospective, single blind, randomized, cross-over trial. After two weeks of wash-out from alcoholic beverages, subjects were randomized to a cross-over design A-B or B-A of a 2-week treatment with white wine (4 ml/kg body weight, 0.48 g/kg of alcohol 12%, corresponding to 2-3 glasses/daily) and extra-virgin olive oil (treatment A) or extra-virgin olive oil alone (treatment B). The two study periods were separated by a two-week wash-out period. At baseline and at the end of each treatment, plasma levels of inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8) concentration were determined. Urinary levels of Tyr, OH-Tyr, and their metabolites were measured at the same time. RESULTS: During combined consumption of white wine and extra-virgin olive oil (treatment A), plasma levels of CRP and IL-6 decreased from 4.1 ± 1.8 to 2.4 ± 1.9 mg/l (p < 0.05) and from 5.3 ± 3.2 to 3.4 ± 2.3 mg/l (p < 0.05) in CKD patients. CRP decreased from 2.6 ± 1.2 to 1.9 ± 0.9 mg/l (p < 0.05), and IL-6 decreased from 2.2 ± 1.8 to 1.7 ± 1.3 mg/l (p = ns) in healthy volunteers. No significant variation versus baseline was observed during treatment B. A significant increase in urinary Tyr and OH-Tyr was observed during treatment A (white wine and extra-virgin olive oil). CONCLUSIONS: Plasma markers of chronic inflammation were significantly reduced in CKD patients during the combined consumption of white wine and olive oil, suggesting a possible anti-inflammatory effect of this nutritional intervention.

A pharmacoeconomic analysis of phosphate binders cost-effectiveness in the RISCAVID study.

BACKGROUND: A pharmacoeconomic analysis of the RISCAVID database aimed at assessing the cost effectiveness of phosphate binders in preventing CV mortality and morbidity over 7 years was performed. METHODS: Morbid or fatal events occurring in 750 chronic HD patients were recorded. Statistical analysis evaluated the distribution of variables and the effect of sevelamer on survival. A cost-effectiveness evaluation was performed using a probabilistic model based on a Markov chain. RESULTS: Multivariate analysis showed that treatment with sevelamer was associated with a reduced stroke incidence by 52% (p = 0.04) and reduced levels of C-reactive protein (p < 0.01). Cost-effectiveness evaluation evidenced a 33% decrease in hospital-days for patients treated with sevelamer, with and without comorbidities compared to patients undergoing calcium binders treatment. CONCLUSION: Treatment with sevelamer was associated with a reduced risk of stroke in HD patients, with a clear saving on disease-related costs for the Italian National Healthcare System.

Serum alkaline phosphatase is a strong predictor of mortality in ESKD patients: analysis of the RISCAVID cohort.

BACKGROUND: Mortality in hemodialysis (HD) patients remains unacceptably high compared with that of the general population and despite the continuous improvement of dialysis techniques. This study aimed to assess the role of alkaline phosphatase serum levels on cardiovascular and overall mortality in the RISCAVID study cohort through a long follow-up period, looking for associations with known risk factors for poor outcome. METHODS: In June 2004, a prospective observational study was started focusing on the cardiovascular risk in hemodialysis patients who lived in the north-west area of Tuscany (RISCAVID, "RISchio CArdiovascolare nei pazienti afferenti all'Area Vasta In Dialisi"). The RISCAVID cohort included 572 prevalent patients on maintenance HD for at least three months. Morbid or fatal events were prospectively recorded at 6-month intervals for a follow up time of 216 months. RESULTS: In univariable Cox regression analysis, dialysis technique, Geriatric Nutritional Risk Index, peripheral vascular disease, and intact parathyroid hormone and total calcium serum levels were significantly associated with baseline alkaline phosphatase serum levels. Cox multivariable analysis showed that elevated serum alkaline phosphatase levels (the highest quartile), advanced age, dialysis vintage, type of vascular access, Geriatric Nutritional Risk Index, C-reactive protein and calcium serum levels, history of cardiovascular disease and peripheral vascular disease were independent predictors of overall mortality in maintenance HD patients. The fourth quartile of alkaline phosphatase was associated with all-cause 10-year mortality (HR: 1.47; 95% CI: 1.177-1.834) with a 47% increase with respect to the 1st, 2nd, and 3rd quartiles. This was also observed for 18-year all-cause mortality. CONCLUSIONS: Adjusted proportional analysis showed the alkaline phosphatase value to be an independent and powerful predictor of overall mortality in the hemodialysis population.

Post-dilution on line haemodiafiltration with citrate dialysate: first clinical experience in chronic dialysis patients.

BACKGROUND: Citrate has anticoagulative properties and favorable effects on inflammation, but it has the potential hazards of inducing hypocalcemia. Bicarbonate dialysate (BHD) replacing citrate for acetate is now used in chronic haemodialysis but has never been tested in postdilution online haemodiafiltration (OL-HDF). METHODS: Thirteen chronic stable dialysis patients were enrolled in a pilot, short-term study. Patients underwent one week (3 dialysis sessions) of BHD with 0.8 mmol/L citrate dialysate, followed by one week of postdilution high volume OL-HDF with standard bicarbonate dialysate, and one week of high volume OL-HDF with 0.8 mmol/L citrate dialysate. RESULTS: In citrate OL-HDF pretreatment plasma levels of C-reactive protein and ß 2-microglobulin were significantly reduced; intra-treatment plasma acetate levels increased in the former technique and decreased in the latter. During both citrate techniques (OL-HDF and HD) ionized calcium levels remained stable within the normal range. CONCLUSIONS: Should our promising results be confirmed in a long-term study on a wider population, then OL-HDF with citrate dialysate may represent a further step in improving dialysis biocompatibility.

Mediterranean Dietary Pattern Adjusted for CKD Patients: The MedRen Diet.

A number of studies in the general population showed that healthy dietary patterns, such as the Mediterranean Diet, can improve or prevent the development of several chronic diseases and are associated with a significant reduction in all-cause and cardiovascular mortality. The Mediterranean diet may also have favorable effects for the prevention of chronic kidney disease (CKD), but no evidence of renoprotection exists in CKD patients. The Mediterranean Renal (MedRen) diet is an adaptation of the Mediterranean diet recommendations comprising a quantitative reduction in the RDA values of protein, salt and phosphate intake for the general population. Hence, MedRen supplies 0.8 g/Kg of protein, 6 g of salt and less than 800 mg of phosphate daily. Obviously, there is a preference for products of plant origin, which contain more alkali, fibers, unsaturated fatty acids than animal-based food. The MedRen diet can be implemented easily in mild-to-moderate stages of CKD with good results, both in terms of adherence to prescriptions and metabolic compensation. In our opinion, it should be the first step of CKD stage 3 nutritional management. This paper describes the features and reports our experience in the implementation of the MedRen diet as an early nutritional approach to CKD.

ABCs of hemodiafiltration prescription: The Pisa style.

In end-stage kidney disease patients, hemodiafiltration, a mixed diffusive-convective technique, has shown beneficial effects in terms of improvement of anemia, inflammation, mineral bone disorders, malnutrition and cardiovascular stability. Greater convective volume exchange was also associated with improved overall and cardiovascular survival. However, absolute target threshold volume would be difficult to define and achieve in daily clinical practice, mainly because of differences in patient size. Convective volumes standardized for body surface area would appear to be the simplest approach in clinical practice. Several factors can affect achievement of optimal convective volume, with vascular access being the main limiting factor. Based on our own clinical experience, hemodiafiltration is a more effective and preferable dialysis technique but only when a target convective volume greater than 20 L can be achieved. Conversely, standard high flux hemodialysis or expanded hemodialysis may be helpful and valuable alternative dialysis techniques.

Diagnosis, Prevalence and Significance of Obesity in a Cohort of CKD Patients.

BACKGROUND: data regarding the association between obesity and morbidity/mortality in patients with chronic kidney disease (CKD) are uncertain and sometimes contradictory. The aims of our study were to determine the associations among different measures of obesity and adiposity, and the risk of all-cause mortality or dialysis entry in stage 3-5 CKD patients. MATERIALS: this observational cohort study included 178 CKD patients followed for a median of 71 months. Biochemistry, anthropometric measures such as body mass index (BMI), waist-to-hip ratio, mid-arm muscle circumference (MAMC) and body composition by bioimpedance analysis were evaluated. RESULTS: we found a weak agreement between BMI and other measures of adiposity. In multivariable regression analysis, all measures of obesity such as BMI, waist circumference and waist-to-height ratio were not associated with dialysis entry and/or mortality. Instead, MAMC was associated with dialysis entry HR 0.82 [95% CI: 0.75-0.89] and high FM% with mortality HR 2.08 [95% CI: 1.04-4.18]. CONCLUSIONS: in our CKD population, lower MAMC was predictive of dialysis commencing, while a higher percentage of fatty mass was a predictor of mortality. Instead, obesity, as defined by BMI, is not associated with dialysis commencing or all-cause mortality.

Nutritional Treatment as a Synergic Intervention to Pharmacological Therapy in CKD Patients.

Nutritional and pharmacological therapies represent the basis for non-dialysis management of CKD patients. Both kinds of treatments have specific and unchangeable features and, in certain cases, they also have a synergic action. For instance, dietary sodium restriction enhances the anti-proteinuric and anti-hypertensive effects of RAAS inhibitors, low protein intake reduces insulin resistance and enhances responsiveness to epoetin therapy, and phosphate restriction cooperates with phosphate binders to reduce the net phosphate intake and its consequences on mineral metabolism. It can also be speculated that a reduction in either protein or salt intake can potentially amplify the anti-proteinuric and reno-protective effects of SGLT2 inhibitors. Therefore, the synergic use of nutritional therapy and medications optimizes CKD treatment. Quality of care management is improved and becomes more effective when compared to either treatment alone, with lower costs and fewer risks of unwanted side effects. This narrative review summarizes the established evidence of the synergistic action carried out by the combination of nutritional and pharmacological treatments, underlying how they are not alternative but complementary in CKD patient care.

RAASi Therapy Attenuates the Association between 24-h Urinary Potassium Excretion and Dietary Potassium Intake in CKD Patients.

The aim of this study was to evaluate urinary potassium (K) excretion as a reliable marker of dietary K intake, in a cohort of CKD patients with or without Renin-Angiotensin-Aldosterone System (RAAS) inhibitor therapy. One hundred and thirty-eight consecutive out-patients (51 f and 87 m) aged 60 ± 13 years and affected by CKD stage 3-4, who were metabolically and nutritionally stable, entered the study between November 2021 and October 2022. No difference was observed between patients with (n = 85) or without (n = 53) RAAS inhibitor therapy, regarding dietary intakes, blood biochemistry, and 24-h urine excretion parameters. Considering all patients, urinary K showed a weak relationship with eGFR (r = 0.243, p < 0.01), and with dietary K intake (r = 0.184, p < 0.05). Serum K was not associated with dietary K intake, but an inverse relationship was observed with eGFR (r = -0.269, p < 0.01). When patients were examined depending on whether they were receiving RAAS inhibitor therapy, the weak inverse relationship between serum K and eGFR was maintained in both groups. Conversely, urinary K excretion remained positively associated with dietary K intake only in the no RAAS inhibitor group. In conclusion, 24-h urine K excretion may be used as a surrogate of K intake, but RAAS inhibitor therapy reduces the association between 24-h urine K excretion and dietary K intake in CKD patients.

Vitamin D and Calcium Supplementation and Urolithiasis: A Controversial and Multifaceted Relationship.

Patients with urolithiasis, and particularly those with hypercalciuria, frequently have a marked reduction of bone mineral content up to the levels of osteoporosis, with a significant increase in bone fracture risk. For these reasons, the indication to prescribe vitamin D and/or calcium supplementations is very frequent in such patients. On the other hand, both calcium supplementation, and even more vitamin D therapy, can worsen the risk of developing urolithiasis by increasing calcium, phosphate, and oxalate urinary excretion. Despite the clinical and practical relevance of this issue, the evidence on this topic is scarce and contradictory. Therefore, some concerns exist about how and whether to prescribe such supplements to a patient with a history of kidney stones. In this narrative review, we resume some pivotal pathophysiological concepts strictly related to the dealt topic, and we draw some considerations and personal opinions on the pros and cons of such prescriptions. Finally, we share with the reader our pragmatic algorithm for handling the urolithiasis risk in patients who have strong indications to be prescribed vitamin D and calcium supplementations.

Kidney Stone Prevention: Is There a Role for Complementary and Alternative Medicine?

Complementary and alternative medicine (CAM) is often implemented in kidney stone patients. It consists of preparations including different ingredients, such as herbs, probiotics, and vitamins, often together with alkali, that are classified within the dietary supplementation category. The majority of dietary supplements claiming to treat or prevent kidney stones contain ingredients with conflicting or no scientific evidence to support their claims. Clinicians should advise stone formers that the effects of most supplements are unknown or unstudied in humans and that the absence of evidence does not imply absence of potential harm. Unfortunately, the CAM preparation consists of a mix of different molecules, often including alkali, with different potential mechanisms of action and, even when favorable results are reported, the role of the single molecules cannot be assessed. Despite all these concerns, CAM products remain quite popular among kidney stone patients. The scarce knowledge in this field prevents one from recommending CAM products in daily clinical practice; only a weak suggestion for their use in kidney stone patients may be reasonable.

Nutritional knowledge in hemodialysis patients and nurses: focus on phosphorus.

OBJECTIVE: To assess the knowledge of adult hemodialysis patients and nurses working in dialysis units, specifically with regard to knowledge of phosphorus and other nutrients related to dietary management of end-stage renal disease. DESIGN: Cross-sectional cohort study. SETTING: Hemodialysis unit. SUBJECTS: One hundred ninety-one hemodialysis patients and 105 dialysis nurses, as well as 86 control hospital employees who are not health professionals. INTERVENTION: Nutritional knowledge was assessed by a 25-item chronic kidney disease knowledge assessment tool for nutrition, which includes 15 questions on phosphorus and 10 questions on protein, sodium, and potassium knowledge. RESULTS: The scores obtained by patients were much lower than those of nurses (11.6 ± 3.9 vs. 16.0 ± 2.2, P < .001) but slightly higher than those of controls (10.6 ± 3.2, P < .05). Patients with phosphorus serum level >5.5 mg/dL showed chronic kidney disease knowledge assessment tool for nutrition scores similar to those of patients with a serum phosphorus level <5.5 mg/dL. The prevalence of right answers to questions regarding knowledge of phosphorus was lower than that regarding knowledge of the other nutrients, both for patients (38.4% ± 17.8% vs. 57.3% ± 19.9%, P < .001) and nurses (55.6% ± 11.1% vs. 74.8% ± 11.7%, P < .001) as well as for controls (30.7% ± 14.5% vs. 60.1% ± 17.4%, P < .001). CONCLUSIONS: Our study suggests that nutritional knowledge of hemodialysis patients, although higher than the general population, is lower for phosphorus with respect to the other nutrients, such as protein, sodium, and potassium. This occurs even in patients with hyperphosphatemia or those taking phosphate binder medications. Nurses showed the best scores; however, improvement is necessary, especially with regard to knowledge of phosphorus. Training programs on nutrition for nurses and on information for patients should be implemented. They can contribute to achievement of a more effective control of phosphate balance, reduction of costs, and improvement of the quality of care for hemodialysis patients.