New Treatment Options for Hyperkalemia in Patients with Chronic Kidney Disease

Hyperkalemia may cause life-threatening cardiac and neuromuscular alterations, and it is associated with high mortality rates. Its treatment includes a multifaceted approach, guided by potassium levels and clinical presentation. In general, treatment of hyperkalemia may be directed towards stabilizing cell membrane potential, promoting transcellular potassium shift and lowering total K+ body content. The latter can be obtained by dialysis, or by increasing potassium elimination by urine or the gastrointestinal tract. Until recently, the only therapeutic option for increasing fecal K+ excretion was represented by the cation-exchanging resin sodium polystyrene sulfonate. However, despite its common use, the efficacy of this drug has been poorly studied in controlled studies, and concerns about its safety have been reported. Interestingly, new drugs, namely patiromer and sodium zirconium cyclosilicate, have been developed to treat hyperkalemia by increasing gastrointestinal potassium elimination. These medications have proved their efficacy and safety in large clinical trials, involving subjects at high risk of hyperkalemia, such as patients with heart failure and chronic kidney disease. In this review, we discuss the mechanisms of action and the updated data of patiromer and sodium zirconium cyclosilicate, considering that the availability of these new treatment options offers the possibility of improving the management of both acute and chronic hyperkalemia

Librarians into the mirror: meet the others to recognize ourselves

The paper revolves around the key issues of ‘multiplicity’ and ‘exchange’. Multiple are the training courses to become a librarian, and multiple are the disciplines involved, but the traditional skills of cataloguing, classifying and organizing resources are improved by historical and philological approaches: cataloging can thus become an opportunity for study and discovery. Multiple are the library resources, as well as the international library and cultural institutions networks connecting people who deal with cultural heritage. Several huge metadata sharing projects (HPB, CERL Thesaurus, Europeana) meet different librarians’ information needs, and some of them are dedicated to specific resources, such as incunabula (ISTC, GW, Text-Inc). Finally, the recent interest of libraries in Wikipedia (GLAM projects, #1Lib1Ref) proves that libraries are more and more interested in collaborating in non-traditional frameworks too.Thanks to the case study of the BEIC digital library, the authors show how participation in networks fosters perspective thinking: when the daily routine involves discussion and cooperation, it’s easier to get acknowledgment and visibility.Molteplicità e confronto sono i concetti da cui muove questo contributo. Molteplici sono i percorsi di formazione per diventare bibliotecario e diverse le discipline coinvolte, ma le competenze tradizionali per il trattamento delle risorse bibliografiche si integrano con gli approcci derivanti dalla ricerca storica e filologica, e la catalogazione può diventare un’opportunità di studio e di scoperta. Molteplici sono anche le risorse da gestire e valorizzare nel catalogo, così come lo sono le reti fra biblioteche e istituti culturali che collegano a livello internazionale chi si occupa del patrimonio culturale: le diverse esigenze informative dei bibliotecari trovano risposta in grandi progetti di condivisione dei metadati (HPB, CERL Thesaurus, Europeana), alcuni dei quali dedicati a risorse peculiari, come gli incunaboli (ISTC, GW, Text-Inc). Infine, la recente apertura delle biblioteche a Wikipedia esprime la volontà crescente di collaborare anche in contesti non tradizionali (progetti GLAM, #1Lib1Ref).Grazie al case study della biblioteca digitale BEIC, si dimostra quanto contribuire a una rete insegni a pensare in prospettiva: la routine quotidiana si svolge in un’ottica di confronto e cooperazione, al fine di ottenere risultati più autorevoli e visibili

Enhanced myostatin expression and signalling promote tubulointerstitial inflammation in diabetic nephropathy

open13Myostatin (MSTN), a family member of the transforming growth factor (TGF)-β super family, has been detected in the tubuli of pig kidney, but its role in the human kidney is not known. In this study we observed upregulation of MSTN mRNA (~8 to 10-fold increase) both in the glomeruli and tubulointerstitium in diabetic nephropathy (DN). In DN, immunoreactive MSTN was mainly localized in the tubuli and interstitium (∼4-8 fold increase), where it colocalized in CD45+ cells. MSTN was also upregulated in the glomeruli and the arterial vessels. Tubulointerstitial MSTN expression was directly related to interstitial fibrosis (r = 0.54, p < 0.01). In HK-2 tubular epithelial cells, both high (30 mmol) glucose and glycated albumin upregulated MSTN mRNA and its protein (p < 0.05-0.01). MSTN-treated HK-2 cells underwent decreased proliferation, together with NF-kB activation and CCL-2 and SMAD 2,3 overexpression. In addition, MSTN induced intracellular ROS release and upregulated NADPH oxidase, effects which were mediated by ERK activation. In conclusion, our data show that MSTN is expressed in the human kidney and overexpressed in DN, mainly in the tubulointerstitial compartment. Our results also show that MSTN is a strong inducer of proximal tubule activation and suggest that MSTN overexpression contributes to kidney interstitial fibrosis in DN.openVerzola, Daniela; Milanesi, Samantha; Viazzi, Francesca; Ansaldo, Francesca; Saio, Michela; Garibaldi, Silvano; Carta, Annalisa; Costigliolo, Francesca; Salvidio, Gennaro; Barisione, Chiara; Esposito, Pasquale; Garibotto, Giacomo; Picciotto, DanielaVerzola, Daniela; Milanesi, Samantha; Viazzi, Francesca; Ansaldo, Francesca; Saio, Michela; Garibaldi, Silvano; Carta, Annalisa; Costigliolo, Francesca; Salvidio, Gennaro; Barisione, Chiara; Esposito, Pasquale; Garibotto, Giacomo; Picciotto, Daniel

The Organ Handling of Soluble Klotho in Humans

Chronic kidney disease (CKD) reduces both Klotho expression and its shedding into circulation, an effect that accelerates progression and cardiovascular complications. However, the mechanisms that regulate Klotho release by the human kidney are still unknown. Methods: We measured plasma Klotho across the kidney, splanchnic organs and lung in 22 patients (71 \ub1 2 years, estimated glomerular filtration rate [eGFR] 60 \ub1 5.4 mL/min 1.73 m2) during elective diagnostic cardiac catheterizations. Results: Although the Klotho average renal vein concentrations were remarkably higher (by ~9%) than arterial values, the kidney removed Klotho (or was at zero balance) in 7 subjects, indicating that the kidney contribution to systemic Klotho is not constant. Klotho fractional enrichment across the kidney was inversely related to plasma sodium (r = 0.43, p = 0.045) and acid uric acid levels (r = 0.38, p = 0.084) and directly, to renal oxygen extraction (r = 0.56, p = 0.006). In multivariate analysis, renal oxygen extraction was the only predictor of the enrichment of Klotho across the kidney, suggesting the dependence of renal Klotho release on tubular hypoxia or oxidative metabolism. Klotho balance was neutral across the lung. In patients with eGFR <60 mL/min, Klotho was also removed by splanchnic organs (single pass fractional extraction ~11%). Conclusions: The present study identifies kidney oxygen uptake as a predictor of Klotho release, and splanchnic organs as a site for Klotho removal. This study provides new understanding of kidney Klotho release and suggests that modulating kidney oxygen metabolism could increase Klotho delivery, as an option to slow disease progression and blunt organ damage

Antihypertensive Treatment in Diabetic Kidney Disease: The Need for a Patient-Centered Approach

Diabetic kidney disease affects up to forty percent of patients with diabetes during their lifespan. Prevention and treatment of diabetic kidney disease is currently based on optimal glucose and blood pressure control. Renin-angiotensin aldosterone inhibitors are considered the mainstay treatment for hypertension in diabetic patients, especially in the presence of albuminuria. Whether strict blood pressure reduction entails a favorable renal outcome also in non-albuminuric patients is at present unclear. Results of several clinical trials suggest that an overly aggressive blood pressure reduction, especially in the context of profound pharmacologic inhibition of the renin-angiotensin-aldosterone system may result in a paradoxical worsening of renal function. On the basis of this evidence, it is proposed that blood pressure reduction should be tailored in each individual patient according to renal phenotype

Peripheral artery disease and blood pressure profile abnormalities in hemodialysis patients

Patients undergoing chronic hemodialysis (HD) are at increased risk for peripheral artery disease (PAD). Both ankle-brachial index (ABI) and ambulatory blood pressure monitoring (ABPM) in the interdialytic period have been shown to be strong predictors of all-cause mortality

Resistant Hypertension, Time-Updated Blood Pressure Values and Renal Outcome in Type 2 Diabetes Mellitus

BACKGROUND: Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long-term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real-life clinical practice.METHODS AND RESULTS: Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4-year follow-up, were retrieved and analyzed. The association between time-updated BP control (ie, 75% of visits with BP <140/90 mm Hg) and the occurrence of estimated glomerular filtration rate <60 and/or a reduction 6530% from baseline was assessed. At baseline, 17% of patients had aTRH. Over the 4-year follow-up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction 6530% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; P<0.001 respectively), as compared with those with non-aTRH. No association was found between BP control and renal outcomes in non-aTRH, whereas in aTRH, BP control was associated with a 30% (P=0.036) greater risk of developing the renal end points.CONCLUSIONS: ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more-favorable renal outcome in aTRH. The relationship between time-updated BP and renal function seems to be J-shaped, with optimal systolic BP values between 120 and 140 mm Hg

Effects of Late Conversion from Twice-Daily to Once-Daily Slow Release Tacrolimus on the Insulin Resistance Indexes in Kidney Transplant Patients

The use of tacrolimus (Tac) may be involved in the development of new-onset diabetes after transplantation (NODAT) in a dose-related manner. This study aimed to evaluate the effects of a standard twice-daily formulation of Tac (TacBID) vs. the once-daily slow-release formulation (TacOD) on the basal insulin resistance indexes (Homa and McAuley), and related metabolic parameters, in a cohort of kidney transplant patients. We retrospectively evaluated 20 stable renal transplant recipients who were switched from TacBID to TacOD. Blood levels of Tac were analyzed at one-month intervals from 6 months before to 8 months after conversion. Moreover, Homa and McAuley indexes, C-peptide, insulin, HbA1c, uric acid, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol serum levels and their associations with Tac levels were evaluated. We observed a significant decrease in Tac exposure (8.5 ± 2 ng/mL, CV 0.23 vs. 6.1 ± 1.9 ng/mL, CV 0.31, TacBID vs. TacOD periods, p 0.05) and McAuley indexes (7.12 ± 1 vs. 7.58 ± 1.4, p > 0.05). Similarly, blood levels of glucose, insulin, HbA1c, lipids, and uric acid were unchanged between the two periods, while C-peptide resulted significantly lower after conversion to TacOD. These data suggest that in kidney transplant recipients, reduced Tac exposure has no significant effects on basal insulin sensitivity indexes and metabolic parameters