BackgroundMetabolic acidosis is associated with accelerated progression of chronic kidney disease (CKD). Whether treatment of metabolic acidosis with sodium bicarbonate improves kidney and patient survival in CKD is unclear.MethodsWe conducted a randomized (ratio 1:1). open-label, controlled trial (NCT number: NCT01640119. www.clinicaltrials.gov) to determine the effect in patients with CKD stage 3–5 of treatment of metabolic acidosis with sodium bicarbonate (SB) on creatinine doubling (primary endpoint), all-cause mortality and time to renal replacement therapy compared to standard care (SC) over 36-months. Parametric, non-parametric tests and survival analyses were used to assess the effect of SB on these outcomes.ResultsA total of 376 and 364 individuals with mean (SD) age 67.8 (14.9) years, creatinine clearance 30 (12) ml/min, and serum bicarbonate 21.5 (2.4) mmol/l were enrolled in SB and SC, respectively. Mean (SD) follow-up was 29.6 (9.8) vs 30.3 (10.7) months in SC and SB. respectively. The mean (SD) daily doses of SB was 1.13 (0.10). 1.12 (0.11). and 1.09 (0.12) mmol/kg*bw/day in the first, second and third year of follow-up, respectively. A total of 87 participants reached the primary endpoint [62 (17.0%) in SC vs 25 (6.6%) in SB, p < 0.001). Similarly, 71 participants [45 (12.3%) in SC and 26 (6.9%) in SB, p = 0.016] started dialysis while 37 participants [25 (6.8%) in SC and 12 (3.1%) in SB, p = 0.004] died. There were no significant effect of SB on blood pressure, total body weight or hospitalizations.ConclusionIn persons with CKD 3–5 without advanced stages of chronic heart failure, treatment of metabolic acidosis with sodium bicarbonate is safe and improves kidney and patient survival.Electronic supplementary materialThe online version of this article (10.1007/s40620-019-00656-5) contains supplementary material, which is available to authorized users.

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The Bardet Biedl syndrome (BBS) is a rare inherited disorder considered a model of non-motile ciliopathy. It is in fact caused by mutations of genes encoding for proteins mainly localized to the base of the cilium. Clinical features of BBS patients are widely shared with patients suffering from other ciliopathies, especially autosomal recessive syndromic disorders; moreover, mutations in cilia-related genes can cause different clinical ciliopathy entities. Besides the best-known clinical features, as retinal degeneration, learning disabilities, polydactyly, obesity and renal defects, several additional clinical signs have been reported in BBS, expanding our understanding of the complexity of its clinical spectrum. The present review aims to describe the current knowledge of BBS i) pathophysiology, ii) clinical manifestations, highlighting both the most common and the less described features, iii) current and future perspective for treatment.

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

Thyroid hormones affect the functions of several organs including the heart and kidney. Using isolated left papillary muscles we have investigated the action of thyroid hormones on the mechanical and electrical properties of the heart. We found that pure hypothyroidism causes a depression in contractile and electrical parameters, but we noticed that superimposed hypoparathyroidism accounts for the marked prolongation in contractile kinetics and action potential duration. At kidney level we have shown that thyroid hormones affect proximal tubular sodium transport and this effect is only partially mediated by the action of thyroid hormones on Na-K-ATPase activity. Using the micropuncture technique, we hypothesized that the early effect of thyroid hormone action is on the potassium permeability of proximal tubular cell membrane. This latter effect would explain the increase in isotonic fluid reabsorption through an increase in the driving force for sodium. Finally, hypothyroid patients have a decrease in glomerular filtration rate and renal plasma flow that are completely reversed by thyroxine administration. On the other hand, hyperthyroid subjects exhibit a significant increase in both parameters.

Administration of rMnSOD prevents CsA-mediated impairment of the GFR along with morphological alteration. This effect could be related to the inhibition of ROS.

H2S is the third endogenous gaseous mediator, after nitric oxide and carbon monoxide, possessing pleiotropic effects, including cytoprotection and anti-inflammatory action. We analyzed, in an in vitro model entailing monocyte adhesion to an endothelial monolayer, the changes induced by H2S on various potential targets, including cytokines, chemokines, and proteases, playing a crucial role in inflammation and cell adhesion. Results show that H2S prevents the increase in monocyte adhesion induced by tumor necrosis factor-α (TNF-α). Under these conditions, downregulation of monocyte chemoattractant protein-1 (MCP-1), chemokine C-C motif receptor 2, and increase of cluster of differentiation 36 could be detected in monocytes. In endothelial cells, H2 S treatment reduces the increase in MCP-1, inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, and of a disintegrin and metalloproteinase metallopeptidase domain 17 (ADAM17), both at the gene expression and protein levels. Cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase, the major H2S forming enzymes, are downregulated in endothelial cells. In addition, H2S significantly reduces activation of ADAM17 by PMA in endothelial cells, with consequent reduction of both ADAM17-dependent TNF-α ectodomain shedding and MCP-1 release. In conclusion, H2S is able to prevent endothelial activation by hampering endothelial activation, triggered by TNF-α. The mechanism of this protective effect is mainly mediated by down-modulation of ADAM17-dependent TNF-converting enzyme (TACE) activity with consequent inhibition of soluble TNF-α shedding and its relevant MCP-1 release in the medium. These results are discussed in the light of the potential protective role of H2S in pro-inflammatory and pro-atherogenic processes, such as chronic renal failure.