Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge.

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Successful wound healing by autologous peripheral blood mononuclear cell therapy in a diabetic patient on hemodialysis with no-option critical limb ischemia: a case report.

Peripheral artery disease is a common condition in patients on chronic dialysis treatment, end-stage kidney failure itself being a risk factor. The most severe stage of peripheral artery disease, critical limb ischemia, causes marked chronic pain and is associated with risk of limb loss. Despite improvements in revascularization procedures, the results of limb salvage procedures among dialysis patients remains poor, and lower extremity amputation is associated with high mortality and grim socio-economic implications. We report on a limb salvage approach that was successfully employed in a 74-year-old woman on hemodialysis suffering from no-option critical limb ischemia complicated by diabetic foot infection, i.e. otherwise a candidate for major amputation. The approach consists in implanting in the wound bed of the affected limb a concentrate of autologous peripheral blood mononuclear cells collected from the peripheral blood of the patient using a selective filtration separation system. The procedure, performed by a vascular surgeon in an outpatient setting and sterile conditions, was repeated three times at intervals of 15 days, and was well tolerated; no adverse safety signals were observed. Complete wound healing was obtained, with successful limb rescue.

Treatment Options for Anemia in Kidney Transplant Patients: A Review.

Anemia is common after kidney transplantation. The etiology may be multifactorial, such as causes of anemia in the general population and causes that are unique to the kidney transplant setting. Posttransplant anemia, particularly when severe, may be associated with adverse effects such as graft failure, mortality, and a decline in kidney function. After careful investigation, that is, having excluded or treated reversible causes of anemia, treatment of anemia in patients with a kidney transplant is based on iron supplementation or erythropoiesis-stimulating agents (ESA), although there are no specific guidelines on anemia management in this patient population. Iron therapy is often needed, but optimal and safe iron-deficiency management strategies remain to be defined. Evidence suggests that ESAs are safe and potentially associated with favorable outcomes. Better graft function has been reported with ESA use targeting hemoglobin levels higher than those recommended in the general population with chronic kidney disease and with no apparent increased risk of cardiovascular events. These results require further investigation. Data on the use of hypoxia-inducible factor inhibitors are limited. Prevention and treatment of anemia in kidney transplantation can improve patients' quality of life, life expectancy, allograft function, and survival.

Independent Prognostic and Predictive Role of Interstitial Macrophages in Kidney Biopsies of IgA Nephropathy Patients.

A relevant percentage of IgAN patients experience a progressive decline in kidney function. According to the KDIGO guidelines, proteinuria and eGFR are the only validated prognostic markers. The role of interstitial macrophages in kidney biopsies of IgAN patients and the outcome of patients treated with renin-angiotensin system inhibitors (RASBs) alone or combined with glucocorticoids were evaluated. Clinical and laboratory records (age, gender, hypertension, hematuria, proteinuria, eGFR, serum creatinine, and therapy), MEST-C parameters of the Oxford classification, C4d deposition, peritubular capillaries, and glomerular and interstitial macrophages in 47 IgAN patients undergoing kidney biopsy consecutively between 2003 and 2016 were examined. A high number of interstitial macrophages significantly correlated with peritubular capillary rarefaction and impairment of kidney function. Cox's multivariable regression analysis revealed that a value > 19.5 macrophages/HPF behaved as an independent marker of an unfavorable outcome. Patients exhibiting > 19.5 macrophages/HPF treated at the time of diagnosis with RASBs combined with methylprednisolone had an estimated probability of a favorable outcome higher than patients treated with RASBs alone. Thus, a value > 19.5 macrophages/HPF in IgAN biopsies can predict an unfavorable outcome and endorse a well-timed administration of glucocorticoids. Studies evaluating urine biomarkers associated with peritubular capillary rarefaction in patients with marked macrophage infiltration may help personalized treatment decisions.

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study.

BACKGROUND: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. METHODS: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. RESULTS: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan-Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387-0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465-0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). CONCLUSIONS: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.

Biomarker-Development Proteomics in Kidney Transplantation: An Updated Review.

Kidney transplantation (KT) is the optimal therapeutic strategy for patients with end-stage renal disease. The key to post-transplantation management is careful surveillance of allograft function. Kidney injury may occur from several different causes that require different patient management approaches. However, routine clinical monitoring has several limitations and detects alterations only at a later stage of graft damage. Accurate new noninvasive biomarker molecules are clearly needed for continuous monitoring after KT in the hope that early diagnosis of allograft dysfunction will lead to an improvement in the clinical outcome. The advent of "omics sciences", and in particular of proteomic technologies, has revolutionized medical research. Proteomic technologies allow us to achieve the identification, quantification, and functional characterization of proteins/peptides in biological samples such as urine or blood through supervised or targeted analysis. Many studies have investigated proteomic techniques as potential molecular markers discriminating among or predicting allograft outcomes. Proteomic studies in KT have explored the whole transplant process: donor, organ procurement, preservation, and posttransplant surgery. The current article reviews the most recent findings on proteomic studies in the setting of renal transplantation in order to better understand the effective potential of this new diagnostic approach.

Chyloperitoneum in Peritoneal Dialysis Secondary to Calcium Channel Blocker Use: Case Series and Literature Review.

Chyloperitoneum (chylous ascites) is a rare complication of peritoneal dialysis (PD). Its causes may be traumatic and nontraumatic, associated with neoplastic disease, autoimmune disease, retroperitoneal fibrosis, or rarely calcium antagonist use. We describe six cases of chyloperitoneum occurring in patients on PD as a sequel to calcium channel blocker use. The dialysis modality was automated PD (two patients) and continuous ambulatory PD (the rest of the patients). The duration of PD ranged from a few days to 8 years. All patients had a cloudy peritoneal dialysate, characterized by a negative leukocyte count and sterile culture tests for common germs and fungi. Except for in one case, the cloudy peritoneal dialysate appeared shortly after the initiation of calcium channel blockers (manidipine, n = 2; lercanidipine, n = 4), and cleared up within 24-72 h after withdrawal of the drug. In one case in which treatment with manidipine was resumed, peritoneal dialysate clouding reappeared. Though turbidity of PD effluent is due in most cases to infectious peritonitis, there are other differential causes including chyloperitoneum. Although uncommon, chyloperitoneum in these patients may be secondary to the use of calcium channel blockers. Being aware of this association can lead to prompt resolution by suspension of the potentially offending drug, avoiding stressful situations for the patient such as hospitalization and invasive diagnostic procedures.

Post-dialysis fatigue: Comparison of bicarbonate hemodialysis and online hemodiafiltration.

INTRODUCTION: The present cross-sectional study aimed to compare the prevalence, the characteristics of post-dialysis fatigue and the length of recovery time after hemodialysis in prevalent end-stage renal disease patients (ESRD) receiving bicarbonate hemodialysis (HD) or hemodiafiltration (HDF). METHODS: Patients were suffering from post-dialysis fatigue if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Moreover, each patient was invited to rate the intensity, duration, and frequency of post-dialysis fatigue from 1 to 5. In order to assess RECOVERY TIME AFTER DIALYSIS, patients were invited to answer to the following single open-ended question: "How long does it take you to recover from a dialysis session?" FINDINGS: We included 335 patients: 252 received HD and 83 received HDF. Post-dialysis fatigue was present in 204 patients (60.9%). Prevalence of post-dialysis fatigue did not differ significantly between patients on HD (62.3%) and on HDF (56.6%; p = 0.430). Median recovery time after dialysis was 180 min [180-240] and did not differ significantly between the two subgroups (180 min [130-240] and 240 min [120-332] p = 0.671, respectively). Median post-dialysis fatigue intensity, duration, and frequency were 3 [1-5], 3 [1-5], and 4 [1-5] and did not differ significantly between patients on HD and on HDF. At the multivariate analysis, age, ADL and hemoglobin levels were the independent predictors of the HDF treatment. DISCUSSION: Prevalence and characteristics of post-dialysis fatigue do not differ significantly between patients receiving bicarbonate HD or HDF.

Efficacy of hemoperfusion with Seraph-100 in series with single pass albumin dialysis in acute hepatitis B infection: A case report.

Acute and acute-on-chronic liver failure is a cause of death in patients suffering from viral hepatitis, and many cases need liver transplantation. Infection from hepatitis B virus may range from asymptomatic to severe acute and fulminant hepatitis. In this setting, treatment is mainly supportive as there is no consensus on antiviral therapy based on non-nucleoside reverse transcriptase inhibitors. Single-pass albumin dialysis is a liver-support technique for patients suffering from liver failure, that has shown effectiveness in the removal of both water-soluble and albumin-bound toxins, which accumulate due to impairment of the liver's cleansing function. We report here the case of a 62-year-old male who presented with a severe acute hepatitis B infection, liver failure, and marked hyperbilirubinemia. Treatment with single-pass albumin dialysis combined with a hemoperfusion device was successful in improving clinical, physiological, and laboratory parameters.

Successful use of single-pass albumin dialysis in the correction of severe hyperbilirubinemia in a case of acute hepatitis E.

INTRODUCTION: Acute liver failure (ALF) is a rare syndrome defined by the rapid loss of liver function in the absence of pre-existing liver disease, which may be secondary to hepatitis A virus, hepatitis E virus (HEV), or to drugs in about 50% of cases. Extracorporeal albumin dialysis enables the elimination of albumin-bound toxins that accumulate in liver failure. METHODS: We report a case of ALF secondary to HEV associated with severe hyperbilirubinemia. Patient was treated with four consecutive sessions of single-pass albumin dialysis (SPAD) carried out setting the following parameters: time: 300 min, Qb: 60 mL/min, Qd: 800-1000 mL/min, dialysate containing 4% albumin, citrate: 3-4 mmol/L. RESULT: SPAD documented good support of liver function. Bilirubin levels were reduced from 22 to 14 g/dL after four treatments. Pruritus was the first clinical sign of improvement. CONCLUSION: SPAD system can represent a safe and effective therapeutic option.

The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

Fibrosis of Peritoneal Membrane as Target of New Therapies in Peritoneal Dialysis.

Peritoneal dialysis (PD) is an efficient renal replacement therapy for patients with end-stage renal disease. Even if it ensures an outcome equivalent to hemodialysis and a better quality of life, in the long-term, PD is associated with the development of peritoneal fibrosis and the consequents patient morbidity and PD technique failure. This unfavorable effect is mostly due to the bio-incompatibility of PD solution (mainly based on high glucose concentration). In the present review, we described the mechanisms and the signaling pathway that governs peritoneal fibrosis, epithelial to mesenchymal transition of mesothelial cells, and angiogenesis. Lastly, we summarize the present and future strategies for developing more biocompatible PD solutions.

Vitamin E (Alpha-Tocopherol) Metabolism and Nutrition in Chronic Kidney Disease.

Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation. This vitamin has also important protein function and gene modulation effects. The metabolism of vitamin E depends on hepatic binding proteins that selectively retain food alpha-tocopherol for incorporation into nascent VLDL and tissue distribution together with esterified cholesterol and triglycerides. Chronic kidney disease (CKD) is a condition of oxidative stress and increased lipid peroxidation, that are associated with alterations of alpha-tocopherol metabolism and function. Specific changes have been reported for the levels of its enzymatic metabolites, including both short-chain and long-chain metabolites, the latter being endowed with regulatory functions on enzymatic and gene expression processes important for the metabolism of lipids and xenobiotics detoxification, as well as for the control of immune and inflammatory processes. Vitamin E therapy has been investigated in CKD using both oral vitamin E protocols and vitamin E-coated hemodialyzers, showing promising results in the secondary prevention of cardiovascular disease, as well as of immune and hematological complications. These therapeutic approaches are reviewed in the present article, together with a narrative excursus on the main findings indicating CKD as a condition of relative deficiency and impaired metabolism of vitamin E.

Biocompatibility of Surface-Modified Membranes for Chronic Hemodialysis Therapy.

Hemodialysis is a life-sustaining therapy for millions of people worldwide. However, despite considerable technical and scientific improvements, results are still not fully satisfactory in terms of morbidity and mortality. The membrane contained in the hemodialyzer is undoubtedly the main determinant of the success and quality of hemodialysis therapy. Membrane properties influence solute removal and the interactions with blood components that define the membrane's biocompatibility. Bioincompatibility is considered a potential contributor to several uremic complications. Thus, the development of more biocompatible polymers used as hemodialyzer membrane is of utmost importance for improving results and clinical patient outcomes. Many different surface-modified membranes for hemodialysis have been manufactured over recent years by varying approaches in the attempt to minimize blood incompatibility. Their main characteristics and clinical results in hemodialysis patients were reviewed in the present article.

[Psychological evaluation of patient on chronic dialysis treatment: comparison between home and hospital replacement techniques].

The psychologist's work at the Nephrology and Dialysis Unit of SS. Annunziata Hospital in Chieti begins at the early stages of chronic kidney disease and continues in pre-dialysis and after renal replacement therapy begins. Psychological intervention aims to provide support to patients and caregivers facing a chronic organ disease, as well as to the health personnel constantly exposed to chronic patients. The perceptual and emotional experience of dialysis changes according to the different modalities of renal replacement therapy: hospital or home hemodialysis, peritoneal dialysis. These different emotional and perceptive experiences seem to emerge while the patient prepares for dialysis and influence the process of accepting and adapting to the disease and its therapy.

[Which future solutions for peritoneal dialysis?]

Peritoneal dialysis is an efficient renal replacement therapy for uremic patients but is currently under-prescribed. This is partly due to the unfavorable effects on peritoneal morphology and function (bioincompatibility) of current glucose-based solutions. Use of standard solutions can cause several peritoneal alterations including inflammation, mesothelial to mesenchymal transition, and neo-angiogenesis. The final step is fibrosis, which reduces the peritoneal filtration capacity and can lead to ultrafiltration failure and transfer of the patient to hemodialysis. Bioincompatibility can be local (peritoneum) but also systemic, due to the excessive absorption of glucose from the dialysate. Several strategies have been adopted to improve the biocompatibility of peritoneal dialysis solutions, based on the alleged causal factors. Some new solutions available on the market contain low glucose degradation products and neutral pH, others contain icodextrin or aminoacids. Clinical benefits have been associated with the use of these solutions, which however have some limitations and a debated biocompatibility profile. More recent strategies include the use of cytoprotective agents or osmo-metabolic agents in the dialysate. In this article, we review the different approaches currently under development to improve the biocompatibility of peritoneal dialysis solution and hence the clinical outcome and the viability of the technique.

How to Improve the Biocompatibility of Peritoneal Dialysis Solutions (without Jeopardizing the Patient's Health).

Peritoneal dialysis (PD) is an important, if underprescribed, modality for the treatment of patients with end-stage kidney disease. Among the barriers to its wider use are the deleterious effects of currently commercially available glucose-based PD solutions on the morphological integrity and function of the peritoneal membrane due to fibrosis. This is primarily driven by hyperglycaemia due to its effects, through multiple cytokine and transcription factor signalling-and their metabolic sequelae-on the synthesis of collagen and other extracellular membrane components. In this review, we outline these interactions and explore how novel PD solution formulations are aimed at utilizing this knowledge to minimise the complications associated with fibrosis, while maintaining adequate rates of ultrafiltration across the peritoneal membrane and preservation of patient urinary volumes. We discuss the development of a new generation of reduced-glucose PD solutions that employ a variety of osmotically active constituents and highlight the biochemical rationale underlying optimization of oxidative metabolism within the peritoneal membrane. They are aimed at achieving optimal clinical outcomes and improving the whole-body metabolic profile of patients, particularly those who are glucose-intolerant, insulin-resistant, or diabetic, and for whom daily exposure to high doses of glucose is contraindicated.

Insulin resistance in cardiovascular disease, uremia, and peritoneal dialysis.

Diabetic nephropathy is highly correlated with the occurrence of other complications of type 1 diabetes (T1D) and type 2 diabetes (T2D) mellitus; for example, hypertension with cardiovascular disease (CVD) being the most frequent cause of death in patients with end-stage renal disease and undergoing renal dialysis. Hyperglycemia and insulin resistance (IR) are responsible for the micro- and macrovascular complications of diabetes through different mechanisms. In particular, IR plays a key role in the etiology of atherosclerosis in both diabetic and non-diabetic patients. IR - exacerbated by organ-level selectivity - is more important than glycemic control per se in determining cardiovascular outcomes. This may be exacerbated by the fact that IR is organ and pathway specific due to the only selective loss of sensitivity to insulin action of specific pathways/processes. Therefore, it is counterintuitive that the use of peritoneal dialysis (PD) in (frequently) diabetic renal disease patients should involve their exposure to high daily doses of glucose peritoneally. In view of the controversy about the causal association between glucose load and CVD in PD patients, we discuss the role that selective IR may play in the progression of CVD in diabetic renal end-stage patients. In discussing these associations, we propose that reducing glucose exposure in PD solutions may be beneficial especially if coupled with strategies that address IR directly, and the avoidance of excessive use of insulin treatment in T2D.

Biological Effects of XyloCore, a Glucose Sparing PD Solution, on Mesothelial Cells: Focus on Mesothelial-Mesenchymal Transition, Inflammation and Angiogenesis.

Glucose-based solutions remain the most used osmotic agents in peritoneal dialysis (PD), but unavoidably they contribute to the loss of peritoneal filtration capacity. Here, we evaluated at a molecular level the effects of XyloCore, a new PD solution with a low glucose content, in mesothelial and endothelial cells. Cell viability, integrity of mesothelial and endothelial cell membrane, activation of mesothelial and endothelial to mesenchymal transition programs, inflammation, and angiogenesis were evaluated by several techniques. Results showed that XyloCore preserves mesothelial and endothelial cell viability and membrane integrity. Moreover XyloCore, unlike glucose-based solutions, does not exert pro-fibrotic, -inflammatory, and -angiogenic effects. Overall, the in vitro evidence suggests that XyloCore could represent a potential biocompatible solution promising better outcomes in clinical practice.