Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia最新文献

Chronic Kidney Disease (CKD) provokes biochemical and systemic alterations, causing bone fragility with an increase in bone fracture risk, extraskeletal calcifications, increased morbidity, and cardiovascular mortality. The complex pathophysiological mechanism causes a syndrome called CKD-MBD (Chronic Kidney Disease - Mineral and Bone Disorders), which includes mineral and bone alterations leading to renal osteodystrophy (ROD). An early diagnosis is therefore essential to prevent the onset of more severe complications. A precise diagnosis of bone disorders and the subsequent administration of the best therapy is difficult without performing a bone biopsy. However, lately, the diagnostic focus is shifting to a series of molecules, the bone turnover markers (BTM), generated by the same bone tissue during the remodeling process, which is proving to be a useful diagnostic tool in the definition of ROD. BTMs are divided into bone formation molecules (amino-terminal propeptide of type 1 procollagen, P1NP; osteocalcin, OC; bone alkaline phosphatase, bALP) and bone resorption molecules (carboxy-terminal cross-linked telopeptide of type 1 collagen, CTX; isoform 5b tartrate-resistant acid phosphatase, TRAP-5b). There are also biomarkers of bone metabolism such as parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and sclerostin. Although PTH is one of the most used molecules, P1NP, bALP, CTX, and TRAP-5b have proven to be superior in the discrimination of low turnover pathologies. The diagnostic capability of these molecules and their potential still require further studies, but clinicians must include BTMs in the diagnostic process of CKD-MBD.

Anaemia is a frequent complication of chronic kidney disease; if severe and untreated, it leads to a worsening of quality of life and an increased risk of resorting to haemotransfusions. Beginning with studies in physio-pathology that began in the late 19th century and continued into the 20th century, the first step was the identification of erythropoietin, then its purification, identification of the gene involved and finally the synthesis of recombinant human erythropoietin and its 'long-acting' analogues. Today, therapy with erythropoiesis-stimulating agents (ESAs), often in combination with martial therapy, is the standard of care for patients with chronic kidney disease and anaemia. Recently, ESAs have been joined by HIF-PHD inhibitors. Unfortunately, both categories of drugs, although effective and well-tolerated in most cases, may be associated with a possible increased cardiovascular and thrombotic risk, especially in particular categories of patients. For this reason, the choice of therapy with ESA and HIF-PHD must be customised in terms of haemoglobin target, molecule type and dosage to be used.

Among the recent advancements in Peritoneal Dialysis, the guidelines on the prevention and treatment of peritonitis, published in March 2022 by the International Society for Peritoneal Dialysis (ISPD), are of particular importance. The ISPD periodically updates these guidelines, with the previous update dating back to 2016. Peritonitis, despite its decreased incidence, remains a significant challenge in PD as it continues to be a major cause of morbidity, mortality, and dropout from the modality. The 2022 ISPD guidelines update the previous recommendations and introduce new ones. These recommendations are evidence-based where evidence is available.

Numerous studies have shown that hyperuricemia (HU) is an independent risk factor for the development of chronic kidney disease (CKD) and cardiovascular events. However, while some evidence suggests that uric acid (UA) may play not only a predictive but also a causal role in these conditions, a robust and definitive demonstration of this is still lacking. Moreover, despite what appears to be a logical rationale supporting the use of so-called 'urate-lowering therapy' (ULT) for nephroprotection in hyperuricemic patients with CKD, studies and meta-analyses on this topic - sometimes burdened by limitations that may have affected their results - have so far provided highly divergent outcomes, leaving uncertainty about whether drug-induced reduction of uricemia can truly slow the progression of CKD and prevent its cardiovascular complications. This article summarizes current knowledge on UA metabolism and the drugs that interfere with it, discusses theories on the possible multiple pathogenic mechanisms underlying HU related kidney damage, and reviews the results and limitations of the most recent studies that have supported or refuted the nephroprotective role of ULT in CKD, fueling an ongoing scientific controversy.

Iron therapy in nephropathic patients can allow optimizing treatment with EPO identifying the minimum effective dose capable of improving the patient's quality of life. The most recent studies on iron metabolism and on the interference of iron deficiency syndrome on the performance of some organs, in particular the myocardium, suggest the need to intervene very early, especially in patients with cardiomyopathy and systolic deficit. Setting up an iron therapy in nephropathic patients requires a correct diagnosis. That is particularly difficult in comorbid and inflamed patients because of the poor diagnostic reliability of the main biomarkers (ferritin and transferrin saturation). We need to spread the use of biomarkers that are not influenced by the inflammatory state, not expensive and easily accessible: reticulocyte hemoglobin could meet these requirements. The Pivotal study has delineated the optimal iron treatment in incident hemodialysis patients, treated with EPO not inflamed with classical biomarkers. It is yet to be determined, however, whether the Pivotal results are reproducible in more comorbid patients, also considering new and different therapeutic scenarios that the use of hypoxia-inducible factor-prolyl hydroxyl inhibitors may determine.

The renin-angiotensin-aldosterone (RAAS) system plays a significant role in renal and cardiovascular pathophysiology, since its increased activity is involved in arterial hypertension, heart failure, and kidney disease. ACEIs and ARBs are essential drugs for nephroprotection: they reduce blood pressure values and albuminuria, both related to cardiovascular damage and CKD progression. The nephroprotective effects are evident in both diabetes mellitus and non-diabetic renal disease, and the initial eGFR fall, if not more than 30%, should be considered as a marker of long-term success of renal protection. To optimize the RAAS inhibition salt intake should be strictly controlled, moreover the effective antiproteinuric dose can often be higher than that used as an antihypertensive. In selected and closely monitored cases, it is also possible to consider dual RAAS blockade. Finally, it should be noted that in patients with advanced CKD RAAS inhibition should not be discontinued, either because it does not give any benefit on GFR or because it increases cardiovascular risk.

Despite the advances in the immunosuppressive therapies and improvements in short term allograft survival, Antibody-mediated rejection (AMR) still represents the leading cause of late allograft failure in kidney transplant recipients. We present an insidious case of late active AMR that evolved into a severe chronic active antibody-mediated rejection, that we treated with a multidrug approach. Then, we review the current literature on the pathogenesis, diagnosis and treatment of AMR. Antibody-mediated rejection (AMR) typically occurs when anti-HLA donor-specific antibodies (DSA) bind to vascular endothelial cells of the kidney graft. DSAs may preexist to transplantation (preformed DSA) or develop after transplantation (de novo DSA). Pathogenetic mechanisms of AMR involve complement-dependent, and -independent inflammatory pathways that are variably activated depending on antigen and antibody characteristics, or on whether rejection develops early (0-6 months) or late (beyond 6 months) post-transplantation. The Banff classification system categorizes AMR rejection into active antibody-mediated rejection, chronic active antibody-mediated rejection, and chronic (inactive) antibody-mediated rejection. Currently, there are no approved therapies, treatment guidelines being based on low-quality evidence. Therefore, standard of care therapy is consensus-based. In early rejection, it is usually based on plasma exchange, intravenous immune globulin, anti-CD20 antibodies, while complement-inhibitor eculizumab is used in severe and/or refractory cases, treatments with. Recent evidence suggests that late AMR may be effectively treated with anti-CD38 therapy, which targets long lived plasma cells and NK cells.

A growing body of experimental and clinical evidence confirms that aldosterone contributes, independently from its classical homeostatic effects, to the pathogenesis and progression of chronic kidney disease (CKD). In fact, the activation of the mineralocorticoid receptor (MR) in the kidney, present at the podocyte, mesangial, endothelial as well as at the tubulointerstitial levels, has been linked to podocyte damage and consequent apoptosis, proliferation of mesangial cells, inflammation of the tubulointerstitial compartment and, more generally, to the final outcome of interstitial fibrosis and glomerular sclerosis. Therefore, blockade of the MR may represent an effective treatment of CKD. Today, within the class of mineralocorticoid receptor antagonists (MRA), several molecules are available, with different pharmacokinetic and pharmacodynamic characteristics. In this brief review we will focus on the characteristics of these molecules and in particular on Finerenone, a new generation, non-steroidal MRA, characterized by minimal side effects and high pharmacological efficacy.

In recent years, the prevalence of chronic kidney disease (CKD) has significantly increased, with an estimated 843.6 million individuals affected in 2017 [1]. This rise is closely linked to the growing incidence of risk factors such as diabetes mellitus and obesity. Patients with diabetic kidney disease (DKD), one of the most common complications of diabetes, are characterized by high cardiovascular morbidity and mortality. Recent evidence indicates that sodium-glucose cotransporter 2 inhibitors (SGLT2i) play a crucial role in reducing the progression of both DKD and CKD, thanks to its nephroprotective and cardioprotective effects. SGLT2i work by decreasing glomerular hyperfiltration, improving tubulo-glomerular feedback, and reducing blood glucose levels.

Anemia is a major complication of chronic kidney disease (CKD). Its prevalence increases with advancing age and progression of kidney disease. The main cause of anemia linked to CKD is represented by the reduction erythropoietin secretion. The increase in cardiovascular risk and mortality is strongly associated with the presence of anemia, and grows with the severity of the anemia, as described in numerous studies. The main therapies for the control of anemia have so far been represented by iron supplementation, the use of synthetic erythropoietin and blood transfusions. Despite the availability of adequate therapies, the prevalence of anemia in CKD continues to be significant. Drugs that inhibit the enzyme prolyl hydroxylase of hypoxia inducible factor (HIF-PHi) are able to mimic a condition of hypoxia and increase the production of endogenous erythropoietin. HIF-PHi therefore represents an important therapeutic alternative for the control of anemia linked to CKD. Numerous studies have confirmed the ability of HIF-PHi to correct anemia and maintain hemoglobin at adequate values; they also highlighted other potential beneficial pleiotropic factors on cholesterol control and iron homeostasis. Further studies are needed to confirm the safety of the drug, especially regarding cardiovascular risk, vascular thrombosis and neoplastic growth. This document highlights the mechanism of action, effects and pharmacological characteristics of HIF-PHi.