The Serum Level of IL-31 in Patients with Chronic Kidney Disease-Associated Pruritus: What Can We Expect?

Chronic-kidney-disease-associated pruritus (CKD-aP) is one of the most common and burdensome dermatological symptoms affecting patients undergoing dialysis, and its etiopathogenesis has still not been fully discovered. This study was designed to investigate the possible contribution of interleukin-31 (IL-31) to the pathogenesis of itch in patients undergoing maintenance hemodialysis (HD). We evaluated the serum level of IL-31 in HD patients with pruritus, in HD patients without pruritus and in healthy controls, as well as its correlation to the severity of itch. The study enrolled 175 adult subjects. The participants were divided into three groups. Group A included 64 patients on maintenance HD with CKD-aP, Group B included 62 patients on maintenance HD not reporting CKD-aP and Group C included 49 healthy controls. Pruritus severity was assessed using the Numerical Rating Scale (NRS), and the serum levels of IL-31 were measured. The results showed that the IL-31 serum level was significantly higher in the itchy group (p < 0.001) in comparison to the patients free from pruritus. Moreover, a marginal trend towards significance (r = 0.242, p = 0.058) was observed between the IL-31 serum level and itch intensity. Our study supports earlier findings on the extended role of IL-31 in the development of CKD-aP.     

Hepatitis B virus infection as a risk factor for chronic kidney disease

ABSTRACT

Introduction: Hepatitis B virus is an important cause of liver disease and has numerous extra-hepatic manifestations. HBV leads to important morbidity and mortality in the general population and recent evidence suggests a role of HBV in the incidence and progression of chronic kidney disease.

Areas covered: The mechanisms underlying the link between HBV and CKD remain unclear. Nucleos(t)ide analogues for the antiviral treatment of HBV are currently available; these drugs are provided with high efficacy even in patients with CKD.

Expert opinion: A recent meta-analysis of clinical studies showed that HBV results in a greater risk of CKD in the general population. According to an updated review (studies were identified from PubMed, EMBASE, and the Cochrane database), we retrieved six clinical studies (n = 1,034,773 unique patients), adjusted RR, 1.41 (95% CI, 1.09; 1.82, P < 0.001). The significant heterogeneity observed precluded more definitive conclusions. Various mechanisms have been cited to explain the greater risk of CKD among HBsAg positive carriers. Novel evidence shows that untreated HBV and therapy with nucleos(t)ide analogues are associated with increased and decreased risk of end-stage renal disease in CKD population, respectively. We recommend that patients with HBV are assessed for kidney function and urinary changes at baseline and over the follow-up.     

Healthcare utilization and direct costs of non-infectious comorbidities in HIV-infected patients in the USA

Objective: To estimate the incremental healthcare utilization and costs associated with common non-infectious comorbid conditions among commercially and Medicaid-insured HIV-infected patients in the US.

Methods: US administrative claims were used to select adult HIV patients with chronic kidney disease (CKD), cardiovascular disease (CVD) events, or fracture/osteoporosis, three common comorbidities that have been associated with HIV and HIV treatment, between 1 January 2004 and 30 June 2013. Propensity score matched controls with no CKD, no CVD events, and no fracture/osteoporosis were identified for comparison. All-cause healthcare utilization and costs were reported as per patient per month (PPPM).

Results: The commercial cohort comprised 381 CKD patients, 624 patients with CVD events, and 774 fracture/osteoporosis patients, and 1013, 1710, and 2081 matched controls, respectively; while the Medicaid HIV cohort comprised 207 CKD and 271 CVD cases, and 516 and 735 matched controls, respectively. There was insufficient Medicaid data for fracture analyses. Across both payers, HIV patients with CKD or CVD events had significantly higher healthcare utilization and costs than controls. The average incremental PPPM costs in HIV patients with CKD were $1403 in the commercial cohort and $3051 in the Medicaid cohort. In those with CVD events, the incremental costs were $2655 (commercial) and $4959 (Medicaid) for HIV patients compared to controls (p?Conclusions: The results suggested a considerable increase in healthcare utilization and costs associated with CKD, CVD and fracture/osteoporosis comorbidities among HIV patients in the past decade. Because these conditions have been associated with treatment, it is critical to consider their impact on costs and outcomes when optimizing patient care.     

From the Gastrointestinal Tract (GIT) to the Kidneys: Live Bacterial Cultures (Probiotics) Mediating Reductions of Uremic Toxin Levels via Free Radical Signaling

A host of compounds are retained in the body of uremic patients, as a consequence of progressive renal failure. Hundreds of compounds have been reported to be retention solutes and many have been proven to have adverse biological activity, and recognized as uremic toxins. The major mechanistic overview considered to contribute to uremic toxin overload implicates glucotoxicity, lipotoxicity, hexosamine, increased polyol pathway activity and the accumulation of advanced glycation end-products (AGEs). Until recently, the gastrointestinal tract (GIT) and its associated micro-biometabolome was a neglected factor in chronic disease development. A systematic underestimation has been to undervalue the contribution of GIT dysbiosis (a gut barrier-associated abnormality) whereby low-level pro-inflammatory processes contribute to chronic kidney disease (CKD) development. Gut dysbiosis provides a plausible clue to the origin of systemic uremic toxin loads encountered in clinical practice and may explain the increasing occurrence of CKD. In this review, we further expand a hypothesis that posits that environmentally triggered and maintained microbiome perturbations drive GIT dysbiosis with resultant uremia. These subtle adaptation responses by the GIT microbiome can be significantly influenced by probiotics with specific metabolic properties, thereby reducing uremic toxins in the gut. The benefit translates to a useful clinical treatment approach for patients diagnosed with CKD. Furthermore, the role of reactive oxygen species (ROS) in different anatomical locales is highlighted as a positive process. Production of ROS in the GIT by the epithelial lining and the commensal microbe cohort is a regulated process, leading to the formation of hydrogen peroxide which acts as an essential second messenger required for normal cellular homeostasis and physiological function. Whilst this critical review has focused on end-stage CKD (type 5), our aim was to build a plausible hypothesis for the administration of probiotics with or without prebiotics for the early treatment of kidney disease. We postulate that targeting healthy ROS production in the gut with probiotics may be more beneficial than any systemic antioxidant therapy (that is proposed to nullify ROS) for the prevention of kidney disease progression. The study and understanding of health-promoting probiotic bacteria is in its infancy; it is complex and intellectually and experimentally challenging.     

Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity.     

CE-MS-Based Identification of Uremic Solutes Specific to Hemodialysis Patients

Uremic toxins are suggested to be involved in the pathophysiology of hemodialysis (HD) patients. However, the profile of uremic solutes in HD patients has not been fully elucidated. In this study using capillary electrophoresis mass spectrometry (CE-MS), we comprehensively quantified the serum concentrations of 122 ionic solutes before and after HD in 11 patients. In addition, we compared the results with those in non-HD patients with chronic kidney disease (CKD) to identify HD patient-specific solutes. We identified 38 solutes whose concentrations were higher in pre-HD than in CKD stage G5. Ten solutes among them did not significantly accumulate in non-HD CKD patients, suggesting that these solutes accumulate specifically in HD patients. We also identified 23 solutes whose concentrations were lower in both pre- and post-HD than in CKD stage G5. The serum levels of 14 solutes among them were not affected by renal function in non-HD patients, suggesting that these solutes tend to be lost specifically in HD patients. Our data demonstrate that HD patients have a markedly different profile of serum uremic solute levels compared to that in non-HD CKD patients. The solutes identified in our study may contribute to the pathophysiology of HD patients.     

Association between Free Light Chain Levels,and Disease Progression and Mortality in Chronic Kidney Disease

Immunoglobulin free light chains (FLCs) form part of the middle molecule group of uremic toxins. Accumulation of FLCs has been observed in patients with chronic kidney disease (CKD). The aim of the present study was to measure FLC levels in patients at different CKD stages and to assess putative associations between FLC levels on one hand and biochemical/clinical parameters and mortality on the other. One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry assays and assays for FLC kappa (κ) and lambda (λ) and other uremic toxins were performed. Vascular calcification was evaluated using radiological techniques. The enrolled patients were prospectively monitored for mortality. Free light chain κ and λ levels were found to be elevated in CKD patients (especially in those on hemodialysis). Furthermore, FLC κ and λ levels were positively correlated with inflammation, aortic calcification and the levels of various uremic toxins levels. A multivariate linear regression analysis indicated that FLC κ and λ levels were independently associated with CKD stages and β2 microglobulin levels. Elevated FLC κ and λ levels appeared to be associated with mortality. However, this association disappeared after adjustment for a propensity score including age, CKD stage and aortic calcification. In conclusion, our results indicate that FLC κ and λ levels are elevated in CKD patients and are associated with inflammation, vascular calcification and levels of other uremic toxins. The observed link between elevated FLC levels and mortality appears to depend on other well-known factors.     

Protein-energy wasting significantly increases healthcare utilization and costs among patients with chronic kidney disease: a propensity-score matched cohort study

Background: Disease-related malnutrition is highly prevalent, and has prognostic implications for patients with chronic kidney disease (CKD); however, few studies have investigated the impact of malnutrition, or protein-energy wasting (PEW), on healthcare utilization and medical expenditure among CKD patients.

Methods: Using claim data from the National Health Insurance in Taiwan, this study identified patients with CKD between 2009–2013 and categorized them into those with mild, moderate, or severe CKD. Cases with PEW after CKD was diagnosed were propensity-score matched with controls in a 1:4 ratio. Healthcare resource utilization metrics were compared, including outpatient and emergency department visits, frequency and duration of hospitalization, and the cumulative costs associated with different CKD severity.

Results: From among 347,501 CKD patients, eligible cohorts of 66,872 with mild CKD (49.2%), 27,122 with moderate CKD (19.9%), and 42,013 with severe CKD (30.9%) were selected. Malnourished CKD patients had significantly higher rates of hospitalization (p?p?=?.015 for mild CKD, p?=?.002 for severe CKD) than non-malnourished controls. Cumulative medical costs for outpatient and emergency visits, and hospitalization, were significantly higher among all malnourished CKD patients than non-malnourished ones (p?p?Conclusions: In a nationally-representative cohort, CKD patients with PEW had significantly more healthcare resource utilization and higher aggregate medical costs than those without, across the spectrum of CKD: preventing PEW in CKD patients should receive high priority if we would like to reduce medical costs.     

Optimising the treatment of hyperphosphatemia and vascular calcification in chronic kidney disease

Accelerated atherosclerosis and vascular calcifications (VC) play a central role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD) patients. Mineral metabolism disorders and increased serum calcium-phosphate product have been recently investigated as inducing factors of cardiovascular calcification. In fact, cardiovascular disease in renal failure appears greatly associated with bone metabolism alterations. Recently, the treatment of hyperphosphatemia in CKD patients changed from either calcium- or aluminium-based phosphate-binders to new free-calcium and aluminium phosphate binders, such as sevelamer hydrochloride and lanthanum carbonate. Therefore, control of serum phosphate in CKD patients becomes crucial in preventing increases in calcium-phosphate product, secondary hyperparathyroidism and ultimately VC.     

Darbepoetin alfa for anemia in chronic kidney disease

Anemia of chronic kidney disease (CKD) is common, yet it is often under-recognized and undertreated, with serious adverse consequences. It is highly responsive to treatment with erythropoiesis-stimulating agents (ESAs). Darbepoetin alfa is a hyperglycosylated ESA that has a lower affinity to the erythropoietin receptor but a longer half-life than recombinant human erythropoietin, irrespective of administration by a subcutaneous or intravenous route. Owing to its pharmacokinetic characteristics, darbepoetin alfa has been used in extended dosing intervals ranging from once every week to once every 4 weeks in CKD patients on dialysis, as well as in CKD patients not on dialysis. Darbepoetin alfa has been shown to be safe and effective in clinical trials. The safety profile of darbepoetin alfa is similar to that of recombinant human erythropoietin. While target hemoglobin levels in CKD anemia remain debatable, treatment of anemia with ESAs has the proven benefits of reducing transfusions and improving quality of life. Darbepoetin alfa has the potential to simplify the treatment of CKD anemia with many advantages, including infrequent dosing, improved patient convenience and compliance, and decreased healthcare resource utilization.     

The smell of renal protection against chronic kidney disease: Hydrogen sulfide offers a potential stinky remedy

Chronic kidney disease (CKD) is a common global health challenge characterized by irreversible pathological processes that reduce kidney function and culminates in development of end-stage renal disease. It is associated with increased morbidity and mortality in addition to increased caregiver burden and higher financial cost. A central player in CKD pathogenesis and progression is renal hypoxia. Renal hypoxia stimulates induction of oxidative and endoplasmic reticulum stress, inflammation and tubulointerstitial fibrosis, which in turn, promote cellular susceptibility and further aggravate hypoxia, thus forming a pathological vicious cycle in CKD progression. Although the importance of CKD is widely appreciated, including improvements in the quality of existing therapies such as dialysis and transplantation, new therapeutic options are limited, as there is still increased morbidity, mortality and poor quality of life among CKD patients. Growing evidence indicates that hydrogen sulfide (H₂S), a small gaseous signaling molecule with an obnoxious smell, accumulates in the renal medulla under hypoxic conditions, and functions as an oxygen sensor that restores oxygen balance and increases medullary flow. Moreover, plasma H₂S level has been recently reported to be markedly reduced in CKD patients and animal models. Also, H₂S has been established to possess potent antioxidant, anti-inflammatory, and anti-fibrotic properties in several experimental models of kidney diseases, suggesting that its supplementation could protect against CKD and retard its progression. The purpose of this review is to discuss current clinical and experimental developments regarding CKD, its pathophysiology, and potential cellular and molecular mechanisms of protection by H₂S in experimental models of CKD.     

Evaluation of the impact of pharmaceutical care service on hospitalized patients with chronic kidney disease in Jordan

Objectives The primary goal of the present study was to implement and evaluate the impact of pharmaceutical care service for hospitalized chronic kidney disease (CKD) patients in Jordan. Setting Nephrology wards of one of the largest general hospitals in Jordan. Methods All patients who were previously diagnosed with CKD by their physician were eligible for inclusion in the study. Recruited patients were fully assessed for treatment related problems (TRPs) by a clinical pharmacist. Pharmaceutical care service was assessed through a systematic, prospective before–after design. Chi Square test was used to investigate association between categorical variables. P value <0.05 was considered to be statistically significant. Main outcome measures Study outcomes included: Process outcomes (prevalence and nature of identified TRPs, clinical significance of TRPs, associated diseases and drugs), General clinical outcomes (Therapeutic outcomes of TRPs) and CKD specific clinical outcomes (Change from baseline in the number of patients receiving appropriate progression modifying therapy and appropriate management of complications). Results 130 patients were included in the study. The average number of the identified TRPs was 5.31. Eighty-six percent of the recommendations were accepted by physicians. Efficacy related problems were the most common TRP category. Seventeen percent of all TRPs were resolved, 5.5 % were improved, and 37.4 % were prevented through the clinical pharmacist interventions. Conclusions The current study indicated that hospitalized patients with CKD suffer from multiple TRPs mostly related to efficacy of medications and patients monitoring. Clinical pharmacists substantially contributed towards the care of hospitalized CKD patients through optimizing progression modifying therapies, medications safety and management of CKD complications. Based on this study it is strongly recommended to implement pharmaceutical care services for hospitalized CKD patients.     

Targeting Uremic Toxins to Prevent Peripheral Vascular Complications in Chronic Kidney Disease

Chronic kidney disease (CKD) exhibits progressive kidney dysfunction and leads to disturbed homeostasis, including accumulation of uremic toxins, activated renin-angiotensin system, and increased oxidative stress and proinflammatory cytokines. Patients with CKD are prone to developing the peripheral vascular disease (PVD), leading to poorer outcomes than those without CKD. Cumulative evidence has showed that the synergy of uremic milieu and PVD could exaggerate vascular complications such as limb ischemia, amputation, stenosis, or thrombosis of a dialysis vascular access, and increase mortality risk. The role of uremic toxins in the pathogenesis of vascular dysfunction in CKD has been investigated. Moreover, growing evidence has shown the promising role of uremic toxins as a therapeutic target for PVD in CKD. This review focused on uremic toxins in the pathophysiology, in vitro and animal models, and current novel clinical approaches in reducing the uremic toxin to prevent peripheral vascular complications in CKD patients.     

Type I IFNs and their role in the development of autoimmune diseases

Background: Since their initial use in the 1980s, IFNs have become an essential component of the therapy for many diseases such as hepatitis and multiple sclerosis. Although they have been extremely useful in conditions that pose therapeutic challenges, complications associated with their use have been widely reported including emerging reports of several autoimmune diseases. Many of these reports have shed light on the pathogenesis of autoimmune disorders and helped to highlight not only the critical role of type I IFNs in defense against viral infections but also the pivotal role they occupy in the interface between innate and adaptive immunity. Many patients with autoimmune disease have increased responsiveness to type I IFNs (α/β), and therapy with these cytokines has induced or unmasked autoimmune disease in many additional patients. Objective: The objective of this paper is to discuss the role of type I IFNs in autoimmunity. Methods: The literature regarding type I IFNs and autoimmunity was reviewed using the Medline database from 1950 to 2009. Search terms included ‘interferon alpha’ and ‘autoimmune disease’ and ‘interferon beta’ and ‘autoimmune disease’. Case reports, case series, reviews and prospective studies were included in the analysis. Results/conclusions: In the literature a variety of autoimmune disorders have reportedly been induced by the use of type I IFNs, being used, although these are primarily in the form of case reports and case series. Nevertheless, there is a growing body of molecular evidence to support the clinical association. The role of IFNs in the induction of autoimmunity is complex with interplay of many genetic and environmental factors that influence the balance between normal and aberrant immune responsiveness, ultimately leading to the observed clinical manifestations.     

Novel drugs and intervention strategies for the treatment of chronic kidney disease

Chronic kidney disease (CKD) is a worldwide health problem. The disease is most often progressive of nature with a high impact on patients and society. It is increasingly recognized that CKD can be detected in the early stages and should be managed as early as possible. Treatment of the cause, but in particular control of the main risk markers, such as high blood pressure, glucose and albuminuria, has been instrumental in delaying the progression to end-stage renal disease (ESRD). However, despite the state of the art therapy, the absolute risk of renal and cardiovascular morbidity and mortality in CKD patients remains devastatingly high. Novel drugs are therefore highly desirable to halt effectively the progressive renal (and cardiovascular) function loss. Recently, several novel strategies have been tested targeting traditional risk factors such as blood pressure (combination therapy of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) and novel mineralocorticoid receptor antagonists) as well as dyslipidaemia (statins) with surprising results. In addition, drug targets specifically related to the kidney, such as vitamin D, uric acid, erythropoietin and phosphate, have been the subject of clinical trials, in some instances with unexpected results. Finally, novel targets including endothelin receptors and inflammatory pathways are increasingly explored as potential avenues to improve renal and cardiovascular protection, albeit that the drugs tested have not been unequivocally successful. In this article we review novel drugs or intervention strategies for the management of CKD, we try to provide explanations for the failure of some promising drugs and hypothesize on the potential success of new strategies.     

Role of Uremic Toxins in Early Vascular Ageing and Calcification

In patients with advanced chronic kidney disease (CKD), the accumulation of uremic toxins, caused by a combination of decreased excretion secondary to reduced kidney function and increased generation secondary to aberrant expression of metabolite genes, interferes with different biological functions of cells and organs, contributing to a state of chronic inflammation and other adverse biologic effects that may cause tissue damage. Several uremic toxins have been implicated in severe vascular smooth muscle cells (VSMCs) changes and other alterations leading to vascular calcification (VC) and early vascular ageing (EVA). The above mentioned are predominant clinical features of patients with CKD, contributing to their exceptionally high cardiovascular mortality. Herein, we present an update on pathophysiological processes and mediators underlying VC and EVA induced by uremic toxins. Moreover, we discuss their clinical impact, and possible therapeutic targets aiming at preventing or ameliorating the harmful effects of uremic toxins on the vasculature.     

Review article: pruritus in cholestatic and other liver diseases

Pruritus is often the most troublesome symptom in patients with chronic liver disease, particularly when cholestasis is a prominent feature. The exact pathogenesis is unknown, but empirical treatment, such as cholestyramine, based on a liver-based origin of pruritus, has been used for many years. Recently, evidence for a central mechanism for pruritus has been obtained and opioid antagonists have been tried clinically with some benefit, but their use is not widespread. In addition, the pruritus associated with intrahepatic cholestasis of pregnancy can now be alleviated in many cases by ursodeoxycholic acid. As it also improves foetal outcome, this should become first-line therapy. We review the pathogenesis and therapy of pruritus, highlighting practical aspects to help with patients with seemingly intractable pruritus.     

Outcomes of secondary hyperparathyroidism in chronic kidney disease and the direct costs of treatment

BACKGROUND: There has been an emphasis over the last several years to identify and treat chronic kidney disease (CKD) and its complications as they evolve rather than waiting until the patient reaches end-stage renal disease (ESRD), also known as CKD stage 5. The number of patients who will be identified and prescribed therapies for complications such as secondary hyperparathyroidism (SHPT) is greater than initially proposed. OBJECTIVE: To review the pathways, complications, management, and estimated treatment costs of CKD-related SHPT. METHODS: An electronic literature search of MEDLINE (January 1980 through January 2007) was conducted for English-language publications using the base search term secondary hyperparathyroidism. To refine subsequent searches, the authors added Boolean operators to the following secondary and tertiary search terms: parathyroid hormone, chronic kidney disease, renal osteodystrophy, adynamic bone disease, vascular calcification, cardiovascular disease, vitamin D, vitamin D analogs, hypercalcemia, hyperphosphatemia, calcimimetics, costs, prevalence, and economics. RESULTS: The initial MEDLINE search produced 278 relevant articles. After refining the search terms, the authors triaged the results for English-language publications relevant to the discussion of SHPT and its complications in CKD, eliminating 149 publications. The remaining 129 publications were accepted for review. These articles represent a growing body of primarily observational evidence that demonstrates that elevated intact parathyroid hormone (PTH) levels cause deleterious physiological results across a variety of organ systems, including the cardiovascular and skeletal systems. Specific complications associated with SHPT are left ventricular hypertrophy (LVH), renal osteodystrophy (ROD), and extraskeletal calcification. Medical management of the PTH/vitamin D/calcium and phosphorus imbalances in SHPT focus on regulating PTH levels via vitamin D therapy. The class of calcimimetics is a newer treatment modality that has favorable effects on biochemical laboratory values, such as serum calcium and phosphorus levels, but current data do not show differences on hard endpoint patient-oriented outcomes compared with standard generic agents. The direct drug costs in April 2007 U.S. dollars of treating CKD-associated elevations in PTH in predialysis patients range from $8.40 per patient per week ($437 per year) for oral generic calcitriol to $88.90 per patient per week ($4,623 per year) for oral paricalcitol (expressed as 85% of average wholesale price [AWP] for brand drugs or 70% of AWP for generic drugs). The direct drug costs of treating SHPT in hemodialysis patients range from $80.20 per patient per week ($4,170 per year) for generic calcitriol (IV) to $278.46 per patient per week ($14,480 per year) for oral cinacalcet. CONCLUSIONS: SHPT causes skeletal and cardiovascular complications in CKD patients. Calcitriol therapy is effective in managing PTH levels, but efforts to reduce the associated hypercalcemia and hyperphosphatemia have led to the development of newer, yet more expensive, vitamin D analogs. With the lack of evidence to support comparative superior outcomes in end-organ disease among SHPT therapy alternatives, future research is still needed to clearly identify which newer agents are most competitive with the historical gold standard of calcitriol therapy.     

Angiotensin receptor blockers: RAAS blockade and renoprotection

ABSTRACT

Introduction: Chronic kidney disease (CKD) is an increasingly prevalent public health concern and is associated with a high risk of adverse cardiovascular outcomes. Renal impairment is frequently associated with hypertension and there is compelling evidence of the benefits of antihypertensive therapy for reducing progression of kidney disease. The central role of the renin-angiotensin-aldosterone system (RAAS) in hypertension and renal disease has led to interest in the ability of RAAS-blocking agents to provide benefits beyond blood pressure control.

Scope: This review explores the mechanisms involved in CKD development, assesses markers of CKD progression, explores the role of the RAAS in renal disease, and examines RAAS blockade as a therapeutic option for renoprotection. For this purpose, a non-systematic literature review was conducted using the Medline database.

Findings: Studies in patients with diabetic renal disease have shown that RAAS blockade with angiotensin converting enzyme (ACE)-inhibitors or angiotensin receptor blockers (ARBs) reduces progression of renal disease. Similarly, several studies have demonstrated the benefits of ACE inhibitors in non-diabetic renal disease, although few studies have been conducted with ARBs in this setting. At present, there is little evidence to determine the relative merits of ARBs and ACE inhibitors in terms of clinical outcomes, although ARBs appear to have advantages in terms of renal haemodynamics and measures of renal function.

Conclusions: The beneficial effects of ARBs, which result from a combination of antihypertensive, haemodynamic, antiproteinuric and pleiotropic mechanisms, provide a strong rationale for considering the use of these agents in the treatment of high-risk patients.     

Expanded Haemodialysis as a Current Strategy to Remove Uremic Toxins

Chronic kidney disease (CKD) is characterized by the retention of solutes named uremic toxins, which strongly associate with high morbidity and mortality. Mounting evidence suggests that targeting uremic toxins and/or their pathways may decrease the risk of cardiovascular disease in CKD patients. Dialysis therapies have been developed to improve removal of uremic toxins. Advances in our understanding of uremic retention solutes as well as improvements in dialysis membranes and techniques (HDx, Expanded Hemodialysis) will offer the opportunity to ameliorate clinical symptoms and outcomes, facilitate personalized and targeted dialysis treatment, and improve quality of life, morbidity and mortality.