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Objectives Obesity is an important risk factor for morbidity and mortality. Vitamin K2 is involved in the production of bone and matrix amino acid g-carboxy-glutamic acid (Gla) proteins (vitamin K-dependent proteins [VKDPs]), regulating bone and vascular calcification (VC). Bone Gla protein (BGP) is involved both in bone mineralization and VCs. We assessed the relationships between vitamin K levels and body mass index (BMI) according to the hypothesis that the impact of BMI on mortality is partly driven by low vitamin K levels. Methods The Vitamin K Italian (VIKI) study included 387 hemodialysis patients from 18 dialysis centers in Italy. We determined plasma levels of bone markers: vitamin K levels, VKDPs, vitamin 25(OH)D, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and routine biochemistry. BMI was classified into the following categories: underweight (BMI 2), normal weight (18.5 ≤ BMI 2), overweight (25 ≤ BMI 2) and obese (BMI ≥ 30 kg/m2). Results 45.2% of patients were overweight or obese. Stratification by BMI demonstrated lower median menaquinone-7 (MK7)/triglycerides levels in obese patients (0.42 ng/mg [0.19, 0.87], p = 0.005). BGP levels were lower in overweight and obese patients (152 mcg/L [83.2, 251] and 104 mcg/L [62.7, 230], p = Conclusions These data are the first to report an inverse relationship between Vitamin K2 levels and BMI in hemodialysis patients. Further studies are needed to confirm these findings and to determine if lower levels of Vitamin K are related to greater morbidity and mortality in this at-risk population.

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017–2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

The efficacy of antiplatelet treatment with aspirin in the primary prevention of major cardiovascular events was questioned during 2018, following a new series of trials that we summarize here in a quick synoptic overview. The three studies involved are the ASPREE trial, the ASCEND study and the ARRIVE trial. These studies all have a double-blind randomized design, and 100 mg/day aspirin was administered with an intention-to-treat approach and against placebo. Age of the enrolled patients, prevalence of diabetes mellitus and geographical location of other studies are just some of the elements analyzed here, in addition to the different problems of cardiovascular events. The ASPREE study observed a marginal reduction of cardiovascular events with the use of aspirin, by approximately 5% with a confidence interval at risk of insignificancy. On the other hand, the increased risk of a hemorrhagic event appeared to be rather robust, resulting between 18% and 62%. The ASCEND study observed a reduction in cardiovascular events of around 12%, offset by an increase in the risk of major bleeding between 9% and 52%. The ARRIVE study did not detect any incidence of major cardiovascular events, while the risk of major bleeding appeared to even double. The evidences of the current literature push us to review a widespread conviction among professionals who fight the war against cardiovascular disease every day: the prescription of aspirin in the primary prevention can no longer happen systematically, and every single prescription need care between benefits and dangers connected to the treatment.

The interactions and feedback mechanisms involved in heart and renal failure are more complex than previously thought and are grouped under the term “cardio-renal axis”. In the last decades, it has always been emphasized that renal dysfunction in patients with heart failure can be attributed exclusively to low renal plasma flow resulting from reduced cardiac output. In the last two decades cardiorenal syndrome has been established to set complex and close interactions between heart and kidney. Cardiologists and nephrologist should interact in their daily clinical practice to provide better patients’ management. In this review, we will point out main features of cardiorenal axis and cardiorenal syndrome to shift into specific sets of management in Italy starting by Guyton’s hypothesis till present days.

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K+) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin–angiotensin–aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K+ homeostasis, and we review the effects of dietary K+ on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K+ secretion in response to an exogenous load, particularly in the context of “occult” CKD, HF, and in patients taking RAASis and/or MRAs.

Background: Vascular calcification (VC) is a marker of cardiovascular (CV) disease and various methods allow for presence and extension assessment in different arterial districts. Nevertheless, it is currently unclear which one of these methods for VC evaluation best predict outcome and if this piece of information adds to the predictive value of traditional CV risk factors in patients receiving hemodialysis (HD). Methods: data of 184 of the 466 patients followed in the Independent study (NCT00710788) were post hoc examined to assess the association three concurrent measures of vascular calcification and all-cause survival. Specifically, coronary artery calcification (CAC) was determined by the Agatston and the volume score while abdominal aorta calcification was determined by plain X-ray of the lumbar spine (Kauppila score (KS)). Survival and regression models as well as metrics of risk recalculation were used to test the association of VC and outcome beyond the Framingham risk score. Results: Middle-age (62.6(15.8) years) men (51%) and women (49%) starting HD were analyzed. Over 36 (median 36, interquartile range: 8&ndash, 36) months of follow-up 69 patients expired. Each measure of VC (CAC or KS) predicted all-cause mortality independently factors commonly associated with all-cause survival (p &lt, 0.001). Far more importantly, each measurement of VC significantly improved risk prediction and patient reclassification (p &lt, 0.001) beyond traditional cardiovascular risk factors. Conclusions: Overall, presence and extension of VC, irrespective of the arterial site, predict risk of all-cause of death in patients starting hemodialysis. Of note, both CAC and KS increase risk stratification beyond traditional CV risk factors. However, future efforts are needed to assess whether a risk-based approach encompassing VC screening to guide HD patient management improves survival.

Background: It is estimated that chronic kidney disease (CKD) accounts globally for 5 to 10 million deaths annually, mainly due to cardiovascular (CV) diseases. Traditional as well as non-traditional CV risk factors such as vascular calcification are believed to drive this disproportionate risk burden. We aimed to investigate the association of coronary artery calcification (CAC) progression with all-cause mortality in patients new to hemodialysis (HD). Methods: Post hoc analysis of the Independent study (NCT00710788). At study inception and after 12 months of follow-up, 414 patients underwent computed tomography imaging for quantification of CAC via the Agatston methods. The square root method was used to assess CAC progression (CACP), and survival analyses were used to test its association with mortality. Results: Over a median follow-up of 36 months, 106 patients died from all causes. Expired patients were older, more likely to be diabetic or to have experienced an atherosclerotic CV event, and exhibited a significantly greater CAC burden (p = 0.002). Survival analyses confirmed an independent association of CAC burden (hazard ratio: 1.29, 95% confidence interval: 1.17–1.44) and CACP (HR: 5.16, 2.61–10.21) with all-cause mortality. CACP mitigated the risk associated with CAC burden (p = 0.002), and adjustment for calcium-free phosphate binder attenuated the strength of the link between CACP and mortality. Conclusions: CAC burden and CACP predict mortality in incident to dialysis patients. However, CACP reduced the risk associated with baseline CAC, and calcium-free phosphate binders attenuated the association of CACP and outcomes, suggesting that CACP modulation may improve survival in this population. Future endeavors are needed to confirm whether drugs or kidney transplantation may attenuate CACP and improve survival in HD patients.

Cardio-renal anemia syndrome. Third part: TherapyIn the previous sections of this chapter the clinical, epidemiological, pathophysiological and diagnostic aspects of cardiorenal anemia syndrome (CR...

Disphosphonates and renal impairmentOsteoporosis and chronic kidney disease (CKD) are two frequent pathological conditions in the adult and geriatric population and often coexist. These conditions ...

Anemia is a common complication associated with congestive heart failure (CHF) and chronic kidney disease (CKD), and is often reported as a component of the cardiorenal syndrome (CRS). The triad an...

Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization. Serum phosphate levels influence fibroblast growth factor 23 (FGF-23) production, a phosphatonin that modulates serum phosphate reabsorption, PTH synthesis, and vitamin D production. Current therapeutic approaches consist of 1) phosphate intake control by diet or phosphate binders, 2) vitamin D by VDR activation, and 3) calcimimetic agents that activate CaSR. Recently, a new long-acting peptide (etelcalcetide) belonging to the calcimimetics class was approved for intravenous use in hemodialysis patients with SHPT. Etelcalcetide binds directly to CaSR, by a sulfide bond, inhibiting the production and secretion of PTH by parathyroid glands. After intravenous administration in rats, etelcalcetide is quickly distributed to the tissues and eliminated by kidneys, while in uremic animals the nonrenal excretion is only 1.2%. In hemodialysis patients, the treatment itself is the main route of elimination. Etelcalcetide in hemodialysis patients with SHPT was more effective than placebo and cinacalcet, with a PTH reduction of >30% in 76% of patients with etelcalcetide versus 10% with placebo. Particular attention was paid to the safety of the drug; the most common adverse event was asymptomatic blood calcium reduction, similar to cinacalcet, while gastrointestinal symptoms were less frequent. This promising new drug available for better control of SHPT will, together with drugs already in use, optimize the treatment to normalize the biochemical parameters.

Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide efficacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in &ldquo, real world&rdquo, setting that is different from randomized controlled trials (RCTs) to (1) evaluate the effectiveness of etelcalcetide in SHPT, (2) to assess calcium, phosphorus, alkaline phosphatase changes, (3) to register gastrointestinal side effects. Data were collected from twenty-three dialysis units with n = 1190 patients on the charge. From this cohort, n = 168 (14%) patients were on treatment with etelcalcetide, and they were evaluated for statistics. A median weekly dose of etelcalcetide was 15 mg (7.5&ndash, 45 mg). Patients were either na&iuml, ve (33%) or switched from cinacalcet to obtain better control of SHPT with reduced side effects or pills burden. Serum parathyroid hormone (PTH) declined over time from a median value of 636 pg/mL to 357 pg/mL. The median time for responders (intact PTH (iPTH) range: two to nine times the upper normal limit) was 53 days, the percentage of responders increased (from baseline 27% to 63%) being similar in switched-patients and na&iuml, ve-patients. Few patients had symptomatic hypocalcemia requiring etelcalcetide withdrawal (four cases (3%) at 30-day control, two cases (2%) at 60-day, one case (1%) at 90-day control). Side effects with etelcalcetide were lower (3&ndash, 4%) than that registered during cinacalcet treatment (53%). Etelcalcetide is a new therapeutic option for SHPT with low side effects and pills burden. Etelcalcetide may improve adherence to therapy, avoiding unremitting SHP. It remains to be assessed whether etelcalcetide may reduce parathyroidectomy, vascular calcification, or mortality. Being etelcalcetide very potent in suppressing PTH levels, even in severe SHPT, future studies should evaluate the potential risk of more adynamic bone disease during long-term therapy.

Background: The perturbation of phosphate homeostasis portends unfavorable outcomes in chronic kidney disease (CKD). However, the absence of randomized clinical trials (RCT) fuels the discussion of whether phosphate or some other phosphorous-related factor(s) such as fibroblast growth factor 23 (FGF-23) mediates the cardiovascular and systemic toxicity. We herein test whether the fractional excretion of phosphate (FeP) as a marker of renal stress to excrete phosphorous predicts unfavorable outcomes in CKD patients. Methods: Retrospective, cross-sectional observational study. For current analysis, an historical cohort of 407 records of CKD stage 3b-5 patients attending between January 2010 and October 2015 at the Nephrology Unit of Solofra (AV), Italy were utilized. Demographic, clinical, laboratory, and outcome data were identified through the subjects&rsquo, medical records. We tested whether quartiles of FeP are associated with the risk of CKD progression or all causes of death. Parametric as well as non-parametric tests, linear and logistic regression, as well as survival analysis were utilized. Results: Overall, we investigated middle-age (mean 66.0, standard deviation 12.3 years) men and women (male 43%) with CKD stage 3b to 5 (creatinine clearance 32.0 (13.3) mL/min). Older age, lower diastolic blood pressure, poor renal function, as well as higher serum phosphate were associated with FeP. Patients with higher FeP were at an increased risk of starting dialysis or dying (hazard ratio 2.40, 95% confidence interval (1.44, 3.99)). Notably, when the two endpoints were analyzed separately, FeP was associated with renal but not all-cause survival. Conclusion: FeP is associated with ESRD, but not all-cause mortality risk in a large cohort of moderate to advanced CKD patients. Future efforts are required to validate FeP as a marker of nephron stress and risk factor for CKD progression in this high-risk population.

Congestion represents a crucial clinical component of both heart failure and cardiorenal syndrome and it has been postulated to modulate heart and kidney cross-link. Diuretic therapy is a corner stone in the treatment patients with heart failure, and renal replacement therapies are mainly used for patients with refractory heart failure who have not reached the worst stages of renal disfunction. Peritoneal dialysis is a home-based therapeutic modality providing both solute clearance and ultrafiltration, together with relief from congestion in decompensated heart failure patients. The following review will focus on sodium removal in refractory decompensated heart failure patients undergoing peritoneal dialysis. (Cardionephrology)

Use of nutritional therapy (NT) in chronic kidney disease (CKD) patients is still debated among nephrologists, but it represents a fundamental point in the conservative treatment of CKD. It has been used for years and it has new goals today, such as (1) the reduction of edema, diuretics, and blood pressure values with a low sodium-content diet; (2) the dose reduction of phosphate levels and phosphate binders; (3) the administration of bicarbonate with vegetables in order to correct metabolic acidosis and delay CKD progression; (4) the reduction of the number and the doses of drugs and chemical substances; and (5) the lowering of urea levels, the cure of intestinal microbioma, and the reduction of cyanates levels (such as indoxyl-sulphate and p-cresol sulphate), which are the most recent known advantages achievable with NT. In conclusion, NT and especially very low protein diet (VLPD) have several beneficial effects in CKD patients and slows the progression of CKD.

Galectin-3 is a 32- to 35-kDa member of the galectin family of b-galactoside-binding lectins, which is characterized by a carbohydrate recognition domain. Through its carbohydrate-binding function, it regulates cell growth, differentiation, and inflammation. It also plays a complex, context-dependent role in the kidneys. During the development, it promotes nephrogenesis and is strongly expressed in the ureteric bud and its derivatives. An increase in the concentration of galectin-3 has been reported to be associated with fibrosis of the kidneys. Elevated levels of plasma galectin-3 are also associated with increased risks of rapid renal function decline, incident chronic kidney disease, and progressive renal impairment, and also with cardiovascular endpoints, infection, and all-cause mortality in patients with renal function impairment. This review discusses a general survey on galectin-3 expressions in nephrogenesis, kidney injury in animal models, clinical renal diseases, and renal transplantation and t...

In this review we analyze the cardiorenal effects of hyperuricemia and try to answer the eternal question of whether it is or is not to be considered a true risk factor in addition to a well-established marker of cardiovascular, cerebrovascular and renal risk.

Traditionally computed tomography (CT) and more recently magnetic resonance (MR) are the imaging modalities of choice for the evaluation of peritoneum and peritoneal cavity in primary and secondary...

Vitamin D represents the precursor of calcitriol, crucial for bone and mineral metabolism. The high prevalence of vitamin D deficiency and the detection of vitamin D receptor (VDR) both in the heart and vessels have focused the interest on potential cardiovascular effects of vitamin D.Although several experimental data showed the protective role of vitamin D, on the other hand vitamin D “overdose” can contribute to heart and vascular calcification.Meta-analyses of randomized-controlled trials (RCTs) underlined the association of vitamin D deficiency and increased cardiovascular morbidity and mortality but no significant improvements on cardiovascular outcomes are provided by the supplementation of vitamin D.The following review provides an update on pathophysiology of vitamin D and vitamin D receptor (VDR) discussing on the association with cardiovascular risk factors and disease and on the role of vitamin D supplementation in preventing cardiovascular disease in chronic kidney disease (CKD) patients.

Cardiovascular disease (CV) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). The increase in cardiac complications in patients with CKD has encouraged ...

Atrial fibrillation (AF) and chronic kidney disease (CKD) are strictly related; several independent risk factors of AF are often frequent in CKD patients. AF prevalence is very common among these patients, ranging between 15% and 20% in advanced stages of CKD. Moreover, the results of several studies showed that AF patients with end stage renal disease (ESRD) have a higher mortality rate than patients with preserved renal function due to an increased incidence of stroke and an unpredicted elevated hemorrhagic risk. Direct oral anticoagulants (DOACs) are currently contraindicated in patients with ESRD and vitamin K antagonists (VKAs), remaining the only drugs allowed, although they show numerous critical issues such as a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. The purpose of this review is to shed light on the applications of DOAC therapy in CKD patients, especially in ESRD patients.

Patients with acute or chronic decompensated heart failure (ADHF) present with various degrees of heart and kidney dysfunction characterizing cardiorenal syndrome (CRS). CRS can be generally defined as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of 1 organ may induce acute or chronic dysfunction of the other. ADHF is a challenge in the management of heart failure. This review provides an overview the pathophysiology of type 1 CRS together with new approaches to treatment in patients with heart failure with worsening renal function or acute kidney disease.

Chronic hyperkalemia in cardiorenal patients: Q&A for the cardio-nephrologists.Chronic hyperkalemia is a serious medical condition often present in patients with chronic kidney disease (CKD) and he...

The authors wish to make the following corrections to the previous publication [...]

In Part One of this two-part series, the clinical and epidemiological aspects of the cardiorenal anemia syndrome (CRAS) were discussed. Anemia is a complication frequently associated with chronic heart failure (CHF) and chronic kidney disease (CKD). Part Two of this review focuses on the diagnostic elements of anemia in cardiorenal syndrome (CRS). Bone marrow biopsy remains the gold standard for the assessment of iron (Fe) stores. However, many other laboratory tests are available, both biochemical and hematological, that are less invasive, more practical and useful for the diagnosis and gradation of iron deficiency (ID). Biochemical tests are based on Fe metabolism and allow the identification of ID before the onset of anemia. Hematologic examinations, on the other hand, based on the morphologic characteristics of the red blood cells are more readily available. New tests are currently available for ID diagnosis before anemia is present. All of these tests are used to determine the type and cause of anemia in a patient with CRS. Unfortunately, there is no single test capable of establishing the diagnosis of ID with or without anemia, but it is necessary to resort to a combination of assessments adapted to the patient’s specific clinical situation. Indeed, every assessment aimed at evaluating the iron profile expresses a different aspect of each compartment of the total body Fe (deposit, transport, metabolic-functional, etc.). Using the various available tests improves diagnostic specificity and enhances differential diagnosis. (Cardionephrology)

Is peritoneal ultrafiltration a useful therapeutic alternative in diuretic resistant heart failure, even in patients with preserved glomerular filtration rate?Some recent clinical trials, here briefly analysed, reported the positive effects of peritoneal ultrafiltration on NYHA class, hospitalization rates and quality of life of decompensated patients.Why this technique has so little fortune among Nephrologists?

Several abnormalities in chronic kidney disease-related mineral and bone disease (CKD-MBD) have emerged as novel risk factors in excess cardiovascular mortality in patients with CKD and end-stage renal disease (ESRD). Hyperphosphatemia, vascular calcifications development, and decreased active vitamin D production, leading to activation of the renin angiotensin system (RAS), have been identified as the primary cause of CKD-MBD-associated mortality in CKD.Recently, the fibroblast growth factor-23 (FGF-23), a newly discovered hormone produced in the bone that regulates phosphate and vitamin D metabolism by the kidney, has been reported as a strong predictor of adverse cardiovascular outcomes in patients with CKD and ESRD.The main physiological functions of FGF-23 are mediated by the activation of the FGF receptor/α-klotho co-receptor complexes in target tissues. Elevated FGF-23 has been associated with left ventricular hypertrophy (LVH), and it has been suggested that FGF-23 may induce myocardial hypertroph...

The autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder in nephrology. Two genes have been implicated in the development of the disease: PKD1 on chromosome 16 (85%) and PKD2 on chromosome 4 (15%). ADPKD is clinically characterized by renal and extrarenal involvement indicated by the onset of cystic and non-cystic manifestations. Since cardiovascular complications are a leading cause of morbidity and mortality, this review aims to analyze cardiac and vascular involvement in ADPKD.Hypertension is a common early symptom, and occurs in approximately 60% of patients before renal dysfunction. The effect of hypertension on the progression to end-stage renal disease makes it the main potentially treatable risk factor in ADPKD.Also, left ventricular hypertrophy occurs frequently in these patients representing another powerful and independent risk factor for cardiovascular morbidity and mortality in ADPKD.Other abnormalities, such as biventricular diastolic dysfunction, endothel...

Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias, and sudden cardiac death represent main causes of morbidity and mortality in patients with chronic kidney disease (CKD). Their pathogenesis relates to the close linkage between heart and kidneys and involves both traditional and non-traditional risk factors. According to the well-established classification of cardio-renal syndrome, the cardiovascular involvement in chronic kidney disease is known as “type 4 cardiorenal syndrome” (chronic renocardiac syndrome).Uremic cardiopathy is mainly characterized by both left ventricular systolic and diastolic impairment, often associated to right heart dysfunction due to the presence of a vascular access for hemodialysis.The typical clinical picture is represented by left ventricular hypertrophy (LVH), the pathogenesis of which is multifactorial and closely linked to elevated blood pressure, vascular stiffness and atherosclerosis.The diagnosis is mainly made by ultrasound...

Cardiorenal syndrome (CRS) includes a broad spectrum of diseases within which both the heart and kidneys are involved, acutely or chronically. An effective classification of CRS in 2008 essentially divides CRS in two main groups, cardiorenal and renocardiac CRS, based on primum movens of disease (cardiac or renal); both cardiorenal and renocardiac CRS are then divided into acute and chronic, according to onset of disease. The fifth type of CRS integrates all cardiorenal involvement induced by systemic disease. This article addresses the pathophysiology, diagnosis, treatment, and outcomes of the 5 distinct types of CRS.

Numerous observations suggest that chronic kidney disease (CKD) is an epidemic condition [...]

Antiretroviral therapy (ART) has significantly improved life expectancy of infected subjects, generating a new epidemiological setting of people aging withHuman Immunodeficiency Virus (HIV). People living with HIV (PLWH), having longer life expectancy, now face several age-related conditions as well as side effects of long-term exposure of ART. Chronic kidney disease (CKD) is a common comorbidity in this population. CKD is a relentlessly progressive disease that may evolve toward end-stage renal disease (ESRD) and significantly affect quality of life and risk of death. Herein, we review current understanding of renal involvement in PLWH, mechanisms and risk factors for CKD as well as strategies for early recognition of renal dysfunction and best care of CKD.

La fibrillazione atriale (FA) rappresenta la più comune forma di aritmia riscontrabile nella pratica clinica quotidiana, soprattutto nei pazienti affetti da cardiopatia ischemica cronica e da malattia renale cronica (CKD), ed è spesso correlata all’età avanzata e alla presenza di altre comorbidità, come ipertensione arteriosa, diabete mellito e vasculopatia polidistrettuale. Negli ultimi 20 anni si è assistito a un progressivo incremento dell’incidenza della fibrillazione atriale nei pazienti affetti da malattia renale cronica, soprattutto nei pazienti sottoposti al trattamento sostitutivo della funzione renale. (Cardionephrology)

Type 5 cardiorenal syndrome (CRS) is a recently defined clinical syndrome for which complete epidemiological data is still missing. Type 5 CRS occurs when heart and kidneys are involved at once. The pathophysiology of type 5 CRS depends on the underlying disease. Acute type 5 CRS results from systemic processes, e.g. sepsis, infections, drugs, toxins, and connective tissue disorders such as lupus, Wegener's granulomatosis, and sarcoidosis. By contrast, the chronic type 5 CRS (i.e. cirrhotic liver disease) has a more insidious onset, as the kidney and cardiac dysfunction may develop slowly until reaching a crucial point leading to full decompensation. Diagnosis is based both on serological (biomarkers of acute cardiorenal disease, creatinine, and GFR levels) and imaging methods (echocardiography and abdominal ultrasound). Therapy is based on management of the underlying disease and treatment of cardiorenal complications (fluid therapy, drugs, and renal replacement therapy devices).

Worldwide, an estimated 200 million people have chronic kidney disease (CKD), whose most common causes include hypertension, arteriosclerosis, and diabetes. About 40% of patients with diabetes develop CKD and intensive blood glucose control through pharmacological intervention can delay CKD progression. Standard therapies for the treatment of type 2 diabetes mellitus include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2–5) and without dose adjustment. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment.

Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers,Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C.Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300-815 mg), which induced a urine output of 8425 mL (interquartile range, 6341-10 528 mL) over the 72-hour intervention period. Levels ofKidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

Ivabradine, heart failure and chronic kidney diseaseIncidence and prevalence of congestive heart failure are raising, especially in western countries. In Europe and in the United States it represents a disabling clinical disease for all injured people and it's accountable for the increase of hospitalization and sanitary costs.European guidelines have underlined the importance of the optimization of pharmacological treatment to improve both patients' outcomes and quality of life.SHIFT trial's results, based on the evaluation of ivabradine's efficacy if added to conventional congestive heart failure's therapy, seem to proceed in that direction.

The association between physical exercise (fitness) and mortality is a definite certainty in the scientific literature.Objective of this review is to analyse in depth the existing evidence of the association between fitness and tendency to develop chronic non-fatal kidney and heart events.While it is undisputed that cardio-respiratory functional capacity is to some extent correlated to physical activity throughout life, can one postulate that a similar reasoning also applies to renal function?

Calciphylaxis, better described as “Calcific uremic arteriolopathy” (CUA), involves about 1–4% of hemodialysis patients all around the world with high mortality rates. We describe a rare clinical case of CUA in peritoneal dialysis patient associated with urological disease. Penile calciphylaxis represents rare clinical complication, and an early diagnosis and multidisciplinary approach are requested. Pathogenesis is still unclear, and therapeutic approaches need more long-term clinical trials to test their efficacy and safety.

Cardiorenal syndromes (CRS) involve disorders of the heart or kidney whereby one organ dysfunction leads to the dysfunction of another. Five types of CRS are defined. While the first 4 types describe acute/chronic cardiorenal or renocardiac syndromes, type-5 CRS refers to secondary CRS or cardiorenal involvement in systemic conditions and describes the concomitant presence of renal and cardiovascular dysfunction. Type-5 CRS is a recently defined clinical syndrome and complete epidemiological data on this entity are still lacking. In the following review, epidemiological, pathophysiological, clinical, and therapeutic approaches to type-5 CRS will be discussed according to more recent findings.

Tricuspid annular plane excursion (TAPSE) measurement in echocardiography is a measure of heart diastolic distensibility: a low TAPSE indicates reduced ventricular distensibility leading to diastolic dysfunction. It is a good prognostic index for cardiac mortality risk in congestive heart failure patients, adding significant prognostic information to the NYHA clinical classification. Our study was designed to evaluate the effect of a single hemodialysis (HD) session on diastolic function and TAPSE, focusing on the effects of vascular access typology. Twenty chronically uremic patients (age 51 ± 10 years, dialytic age 24 ± 8 months), without overt heart disease, underwent conventional two-dimensional and Doppler echocardiography immediately before starting and 15 min after ending a mid-week HD session. Ten patients had distal radiocephalic arterovenous fistula (AVF), and 10 had permanent central venous catheters (CVC). The amount of fluid removed by HD was 2,706 ± 1,047 g/session. HD led to a reduction in TAPSE, left ventricle end-diastole volume, left ventricle end-systole volume, right ventricle end-diastole diameter, peak early transmitral flow velocity, and the ratio of early to late Doppler velocities of diastolic mitral flow. AVF patients showed greater right ventricle diameters versus CVC patients, while TAPSE appeared higher in the latter. Only the AVF patient group showed TAPSE values

This issue of cardionephrology is based on report from 1st Meeting of Cardionephrology Study Group held in Rome last April 2013.Meeting was characterized by multiple multidisciplinary sessions on h...

Purpose The purpose of this study was to assess whether granulocytopenia observed in 3 of 38 patients with essential mixed cryoglobulinemia who were treated with low-dose interferon was due to the underlying disease or to synergistic toxicity of interferon with other drugs. Patients and methods Adverse effects of interferon therapy were monitored in 38 patients affected with type II essential mixed cryoglobulinemia. Patients were treated with 3 million units (MU), daily or on alternate days, of recombinant interferon-alpha 2a (35 patients) or with natural interferon-beta (3 patients). The duration of treatment ranged between 6 and 15 months; the total duration of follow-up, including after therapy, ranged between 8 and 93 months. Results None of 35 patients treated with interferon alone developed significant hematologic alterations. In addition, none of 7 patients treated with angiotensin-converting enzyme (ACE) inhibitors alone showed hematologic toxicity. Three patients who were treated with a combination of interferon and ACE inhibitors developed severe granulocytopenia a few days after starting treatment. Granulocytopenia subsided within 1 to 2 weeks after suspending therapy. Resumption of treatment with this drug combination produced a granulocytopenia relapse in 1 patient. In these 3 patients, interferon treatment alone, or ACE inhibitor monotherapy, was not followed by granulocytopenia. Conclusion Although severe hematologic toxicity rarely develops in patients treated with low-dose interferon, granulocytopenia occurred in all 3 of our patients with mixed cryoglobulinemia who were treated with a combination of low-dose interferon-alpha 2a and ACE inhibitors. Neither drug alone was toxic in any of our cryoglobulinemic patients, indicating a high risk of severe hematologic toxicity for this drug combination, at least in patients with this disease. Physicians should be aware of this danger when using interferon treatment in patients with this, or possibly other, disorder(s) that also require antihypertensive therapy.