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Autosomal dominant polycystic kidney disease (ADPKD) is the most common congenital kidney disorder, generally caused by mutations in the PKD1 and PKD2 genes, coding for polycystins 1 and 2. Its pathogenesis is accompanied by alterations of the cAMP, mTOR, MAPK/ERK, and JAK/STAT pathways. ADPKD is clinically characterized by the formation of many growing cysts with kidney enlargement and a progressive damage to the parenchyma, up to its complete loss of function, and the onset of end‐stage renal disease (ESRD). The current aim of ADPKD therapy is the inhibition of cyst development and retardation of chronic kidney disease progression. Several drugs have been recently included as potential therapies for ADPKD including metformin, the drug of choice for the treatment of type 2 diabetes mellitus, according to its potential inhibitory effects on cystogenesis. In this review, we summarize preclinical and clinical evidence endorsing or rejecting metformin administration in ADPKD evolution and pathological mechanisms. We explored the biology of APDKD and the role of metformin in slowing down cystogenesis searching PubMed and Clinical Trials to identify relevant data from the database inception to December 2020. From our research analysis, evidence for metformin as emerging cure for ADPKD mainly arise from preclinical studies. In fact, clinical studies are still scanty and stronger evidence is awaited. Its effects are likely mediated by inhibition of the ERK pathway and increase of AMPK levels, which are both linked to ADPKD pathogenesis. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is an increasing public health problem. Aging is one of the leading causes, particularly in Western countries, but several comorbidities, such as hypertension and diabetes are involved in its pathogenesis. Thus, the treatment of CKD patient is very complex and requires an integrated strategy. In this context, the holistic approach to the CKD patient and not to the disease itself should be the answer. General practitioners, specialists, voluntary associations, and nonprofit organizations, in addition to the family of the patient, all contribute to the patient care. Moreover, due to the low sensitivity of creatinine values in the early stages of renal failure, its diagnosis often occurs in the advanced phases of the disease. Therefore, the health costs for CKD patients are hardly sustainable by health systems. The reorganization of economic and epidemiological data through new models is necessary to allow the sustainability of the system and to ensure medical care for all patients. In this review, we aim to deal with all the issues about patient care, standards of care, and the impact of chronicity from a global perspective in light of the current state of the Italian healthcare system. [ABSTRACT FROM AUTHOR]

The mechanism of action of fibroblast growth factor‐23 (FGF23) is becoming increasingly clearer as a result of studies that have defined its structure and pleiotropic effects. Furthermore, data are emerging on the effects exerted on this hormone by iron administration. Ten main iron formulations are recognized (with clear differences in composition and possible reactions of intolerance and anaphylaxis), which are indicated for iron deficiency anemia, including nephropathic subjects, as suggested by medical guidelines. With some types of iron formulation (especially iron carboxymaltose) a particular side effect has been observed: hypophosphatemia, mediated by FGF23. This review aims to draw attention to this correlation and the contradiction represented by the presence of both positive and negative modulation by FGF23, with the effects induced by its increase even after long‐term treatment with iron formulation. However, more evidence is needed to understand the reasons for this differential stimulation. [ABSTRACT FROM AUTHOR]

In the general population and in heart disease, pulmonary hypertension (PH) is a strong and independent risk factor for mortality and adverse cardiovascular outcomes. We performed a systematic review and meta‐analysis of longitudinal cohort studies of individuals with chronic kidney disease (CKD) of any‐stage (also including end‐stage kidney disease and kidney transplantation) stratified according to presence/absence of PH. Eighteen eligible studies (10 740 participants) were retrieved. PH had an overall pooled prevalence of 33% (95% CI 28–42) and portended a higher risk of all‐cause mortality (RR 2.08; 1.06–4.08), cardiovascular mortality (RR 3.77; 2.46–5.78) and non‐fatal cardiovascular events (RR 1.60; 1.28–1.99). PH is highly prevalent in CKD and end‐stage kidney disease and may represent a novel factor for mortality and cardiovascular risk stratification, particularly in selected sub‐categories. Future high‐quality research is required to confirm the need for clinical attention on PH in the CKD setting. [ABSTRACT FROM AUTHOR]

Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia‐inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in‐depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis‐stimulating agents. [ABSTRACT FROM AUTHOR]

Hyperphosphatemia is common in patients with chronic renal failure. Phosphate binders are associated with gastric intolerance, representing the main reason of drug discontinuation. The aim of this study was to compare the effects in vitro and in vivo of sevelamer hydrochloride ( SH), sevelamer carbonate ( SC) and lanthanum carbonate ( LC) on gastric microenvironment. We have also evaluated the efficacy and tolerability of these drugs in hemodialysis ( HD) patients. In vitro analysis : Dissolution time, ability to uptake phosphorus, changes in pH starting from gastric milieu and the amount of carbon dioxide ( CO2) produced were the variables analyzed. In vivo analysis: 24-h esophago-gastric pH measurement was evaluated in 24 HD patients treated with phosphate binders and proton pump inhibitor ( PPI). In vitro: LC dissolved over a longer time compared with SC (58 ± 2.4 vs. 12 ± 0.6 min; P < 0.001) and SH (58 ± 2.4 vs. 10.3 ± 0.8 min; P < 0.001), determining the most alkaline pH. SC had the highest chelation power, binding 4.00 × 10−9 mol/L of phosphoric acid. CO2 volume released was increased in LC solution (53.2 ± 7.8) compared to SC (33.9 ± 6.2; P < 0.001) and SH (2.3 ± 1.8; P < 0.001). In vivo: gastric pH increased after administration of phosphate binder. The most alkaline pH was recorded in patients treated with SC. The alkalinization of the gastric environment was not prevented by PPI therapy. 424 episodes of esophageal reflux were registered, 74% of them were alkaline. The LC group was characterized by the highest number of episodes. Sevelamer carbonate had a greater capacity and rapidity to chelate phosphorus, with a mild tolerability, due to its low CO2 production. Sevelamer HCl was the most tolerated chelator because it did not produce CO2, while lanthanum carbonate was the least soluble. [ABSTRACT FROM AUTHOR]

Abnormalities in bone morphology that develop secondary to chronic kidney disease are defined as renal osteodystrophy and are identified by bone biopsy. As systematic and sequential bone biopsy is not practicable on a large number of patients, various chemical bone markers are commonly used to detect the bone remodeling status in chronic kidney disease and to grade bone disease in the clinical setting. Recent literature has considered the effect of absolute levels of parathyroid hormone (PTH) on clinical outcomes and not the measurement of their change over time, the PTH variability. In a retrospective observational study, we examined PTH variability parameters in a group of hemodialysis patients as independent risk factors for high vs. low turnover osteopathy, and investigated their usefulness with respect to commonly used markers of renal osteodystrophy. The study was conducted on 90 chronic hemodialysis patients undergoing regular treatment at the same dialysis centre (Catanzaro, Italy) with standard bicarbonate dialysis. Patients were classified into either high or medium-low turnover osteopathy for the diagnosis based on renal osteodystrophy using the following criteria: PTH ≥ 400 pg/mL associated with bone ALP ≥ 20 ng/mL. We used a regression-based measurement of PTH variability, which was characterized by different parameters: PTH-Res-SD, PTH-Slope, PTH-Intercept, PTH-Abs-Var, and PTH-Res-SD. In our analysis, these parameters of PTH variability were demonstrated to be good independent predictive factors for high turnover osteodystrophy, and they had a greater sensitivity than the use of a single and/or mean PTH measurements in renal osteodystrophy classification. [ABSTRACT FROM AUTHOR]

Hemodialysis patients were found to have increased levels of circulating NGAL; levels fell with dialysis and this correlated with Kt/V. Neutrophil gelatinase-associated lipocalin (NGAL), a small 25 kDa protein strongly induced in injured renal tubular cells, represents an interesting emerging biomarker in the field of clinical nephrology. The aim of the present pilot study was to analyze circulating NGAL levels in a small cohort of 30 patients on chronic haemodialysis (HD), in order to assess any relationships with different laboratory and clinical parameters. Pre- and post-HD levels were higher in patients than in healthy subjects (485.2 ± 49.7 vs 51.2 ± 4.6 ng/mL; P < 0.001; and 167.4 ± 48.0 vs 51.2 ± 4.6 ng/mL; P = 0.01). Furthermore, a single HD session decreased NGAL levels by approximately fourfold (485.2 ± 49.7 vs 167.4 ± 48.0 ng/mL; p:0.01), with a reduction ratio of 73 ± 14%. At baseline, direct and independent correlations were found between NGAL and, respectively, high-sensitivity C-reactive protein (β = 0.34; P = 0.03) and spKt/V (β = 0.35; P = 0.02). The findings showed that HD patients have chronically increased levels of circulating NGAL. However, with a single HD session, a marked reduction was achieved in circulating NGAL values, probably as a result of an important dialytic removal, similar to that observed for other cytokines. Finally, the direct independent correlation found between NGAL and spKt/V raises the question of whether, in the future, NGAL may also become a useful tool in predicting the adequacy of dialysis and in guiding the management of dialysis prescriptions. [ABSTRACT FROM AUTHOR]

Renal damage, which can be caused by gestational anomalies such as pre-eclampsia, carries a risk of gestational complications; the greatest risk being in women who become pregnant while on hemodialysis or peritoneal dialysis. If this rare event occurs, there is a marked increase in the risk of pre-eclampsia, early uterine contractions and hydramnios, hypertensive crisis, preterm delivery and intrauterine growth retard. Furthermore, newborns are almost always of low birthweight. Patients who undergo renal transplantation are another high-risk category. In such cases, the pregnancy itself can compromise the success of the transplant and the immunosuppressive therapy correlated to it can become a threat to the course of the pregnancy and normal fetal growth. Therefore, in view of the lack of appropriate guidelines for the best possible approach to the treatment of women on dialysis or of those with a renal transplantation, it is best to advise these patients against becoming pregnant and/or to provide a valid counselling service illustrating the extreme difficulties and dangers involved in becoming pregnant. [ABSTRACT FROM AUTHOR]

Dramatic removal of potassium during hemodialysis sessions can induce changes in the electrical properties of nerve cells or muscle fibers, which may underlie neuromuscular symptoms referred by end-stage renal disease patients. The primary aim of our study was to investigate the effects of acetate-free biofiltration (AFB) on the amplitude of compound motor action potential (cMAP) obtained after stimulation of the ulnar nerve at the wrist. The secondary aim was to compare the effect of two different potassium removal modalities on cMAP amplitude and to analyze the effects on muscular force by specific dynamometric tests. Twenty-eight patients received dialysis for 4 h, 3 times per week, first with standard AFB with constant potassium (AFB) and then with AFB with a variable concentration of potassium in the dialysis bath (AFBK). The amplitude of cMAP was determined after ulnar nerve stimulation at the wrist at different time intervals: at the start of dialysis; at 15, 45, 90, and 120 min after beginning the session; and at the end of treatment. At the same time intervals, muscle force generation was determined using a dynamometer. Finally, we measured plasma electrolytes, intraerythrocytic potassium, and the electrical membrane potential at rest (REMP) of the erythrocytic membrane. The main finding of this study was a significant reduction of cMAP amplitude in the first 45 min after AFB, which paralleled the reduction in serum potassium levels. Moreover, there was a reduction of muscular strength determined with dynamometric measurements. Potassium removal induced by the two different modalities of AFB may significantly affect myocardial and fibromuscular cells by modulating the electrochemical balance of cell membranes. The transient alteration of the electrical properties on voluntary striated muscle fibers may contribute to the brief reduction in muscular strength we detected in patients who underwent AFB. AFBK can minimize the negative effects of standard AFB treatment on neuromuscular excitability, most likely through a more gentle variation of potassium levels during dialysis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of a 32-year-old woman with antineutrophil cytoplasmic antibody (p-ANCA) associated vasculitis who achieved a successful conception and pregnancy in course of treatment with renal replacement therapy and immunosuppressive drugs.

A letter to the editor is presented about an article on circulating endothelial progenitor cell mobilization in centenarians.