No abstract

Myostatin (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.Myostatin (MSTN), a family member of the transforming growth factor (TGF)-β super family, is a major effector of muscle atrophy in several chronic diseases, including chronic kidney disease (CKD) 1-5 . MSTN has many similarities to TGF-β in structure, signaling pathway and functions 4,5 . After the cleavage of its mature COOH-terminus domain, MSTN binds to the activin-type II receptor B (Act RIIB), and to activin-type II receptor A (Act RIIA) with lower affinity, while recruiting both Activin-type I receptors, ALK4 and ALK5 1,6 . The binding of MSTN and activin to the Act RIIA/B receptor complex activates SMAD2,3-mediated transcription, which accelerates protein breakdown and inhibits protein synthesis 6,7 . By activating SMAD2,3 MSTN also causes fibrosis, since it stimulates fibroblast proliferation and induces its differentiation into myofibroblasts. In addition, MSTN shares with TGF-β1 a positive feed-back loop, with TGF-β1 stimulating MSTN expression, and, conversely, MSTN inducing TGF-β1 secretion 8 .MSTN expression is not only limited to skeletal muscle; low levels of MSTN mRNA are reported in several other types of human tissues, including smooth muscle, cardiac muscle, adipose tissue, the brain, the spleen and circulating leucocytes 1 . MSTN has also been detected in the tubular compartment of the kidney of the pig 9 a species that is anatomically and physiologically comparable to humans 10 , suggesting that MSTN may have functions also in the human kidney.In addition to its influences on protein metabolism, MSTN has many effects on glucose metabolism, and may participate in the pathophysiology of diabetes mellitus. MSTN deficiency protects against high-fat diet-induced obesi...

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.

Pregnancy in women affected by chronic kidney disease (CKD) has become more common in recent years, probably as a consequence of increased CKD prevalence and improvements in the care provided to these patients. Management of this condition requires careful attention since many clinical aspects have to be taken into consideration, including the reciprocal influence of the renal disease and pregnancy, the need for adjustment of the medical treatments and the high risk of maternal and obstetric complications. Nutrition assessment and management is a crucial step in this process, since nutritional status may affect both maternal and fetal health, with potential effects also on the future development of adult diseases in the offspring. Nevertheless, few data are available on the nutritional management of pregnant women with CKD and the main clinical indications are based on small case series or are extrapolated from the general recommendations for non-pregnant CKD patients. In this review, we discuss the main issues regarding the nutritional management of pregnant women with renal diseases, including CKD patients on conservative treatment, patients on dialysis and kidney transplant patients, focusing on their relevance on fetal outcomes and considering the peculiarities of this population and the approaches that could be implemented into clinical practice.