How to Choose the Right Treatment for Membranous Nephropathy.

Membranous nephropathy is an autoimmune disease affecting the glomeruli and is one of the most common causes of nephrotic syndrome. In the absence of any therapy, 35% of patients develop end-stage renal disease. The discovery of autoantibodies such as phospholipase A2 receptor 1, antithrombospondin and neural epidermal growth factor-like 1 protein has greatly helped us to understand the pathogenesis and enable the diagnosis of this disease and to guide its treatment. Depending on the complications of nephrotic syndrome, patients with this disease receive supportive treatment with diuretics, ACE inhibitors or angiotensin-receptor blockers, lipid-lowering agents and anticoagulants. After assessing the risk of progression of end-stage renal disease, patients receive immunosuppressive therapy with various drugs such as cyclophosphamide, steroids, calcineurin inhibitors or rituximab. Since immunosuppressive drugs can cause life-threatening side effects and up to 30% of patients do not respond to therapy, new therapeutic approaches with drugs such as adrenocorticotropic hormone, belimumab, anti-plasma cell antibodies or complement-guided drugs are currently being tested. However, special attention needs to be paid to the choice of therapy in secondary forms or in specific clinical contexts such as membranous disease in children, pregnant women and patients undergoing kidney transplantation.

Hyperphosphatemia in Chronic Kidney Disease: The Search for New Treatment Paradigms and the Role of Tenapanor.

Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular complications and mineral bone disorders. Traditional approaches to address hyperphosphataemia involve implementing dietary phosphate restrictions, administering phosphate binders, and, in cases of end-stage renal disease, resorting to dialysis. Unfortunately, these interventions frequently prove inadequate in maintaining phosphate levels within recommended ranges. Additionally, commonly employed pharmacological agents are not immune to eliciting adverse events, thereby limiting their prescription and therapeutic adherence. There is a growing focus on exploring novel therapeutic strategies in this context. The current discussion centres on tenapanor, a pharmacological agent predominantly acting as a selective inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3). Its mechanism of action involves modulating tight junctions, resulting in reduced sodium absorption and intestinal paracellular permeability to phosphate. Furthermore, tenapanor downregulates sodium-dependent phosphate 2b transport protein (NaPi2b) expression, thereby impeding active transcellular phosphate transport. Clinical trials have elucidated the efficacy and safety profile of tenapanor. This evidence hints at a potential paradigm shift in the management of hyperphosphataemia. However, the burgeoning optimism surrounding tenapanor warrants tempered enthusiasm, as further research remains indispensable. The imperative lies in meticulously delineating its efficacy and safety contours within the crucible of clinical practice. In this review, we synthesize the intricate interplay between hyperphosphataemia and Chronic Kidney Disease-Mineral Bone Disorder, and we discuss the existing pharmacological interventions for hyperphosphataemia and explore emerging treatment paradigms that offer novel perspectives in managing elevated phosphate levels in CKD patients.

Investigational new drugs for the treatment of chronic renal failure: an overview of the literature.

INTRODUCTION: Chronic kidney disease (CKD) is widespread throughout the world, with a high social and health impact. It is considered a 'silent killer' for its sudden onset without symptoms in the early stages of the disease. The main goal of nephrologists is to slow the progression of kidney disease and treat the associated symptoms with a range of new medications. AREAS COVERED: The aim of this systematic review is to analyze the new investigational drugs for the treatment of chronic renal failure. Data were obtained from the available scientific literature and from the ClinicalTrials.gov website. EXPERT OPINION: Among the drugs currently being researched, SGLT2 inhibitors appear to be the most promising drugs for the treatment of CKD, has they have slower progression of CKD and protection of cardiorenal function. An important role in the future of CKD treatment is played by autologous cell-therapy, which appears to be a new frontier in the treatment of CKD. Other therapeutic strategies are currently being investigated and have been shown to slow the progression of CKD. However, further studies are needed to determine whether these approaches may offer benefits in slowing the progression of CKD in the near future.

Pregnancy in Glomerular Disease: From Risk Identification to Counseling and Management.

Background: Pregnancy involves complex hemodynamic and immune adaptations to support the developing fetus. The kidney assumes a pivotal role in orchestrating these mechanisms. However, renal disease poses a potential risk for adverse maternal-fetal outcomes. While kidney function, hypertension, and proteinuria are recognized as key influencers of risk, the mere presence of glomerular disease, independent of these factors, may wield significant impact. Methods: A brief review of the existing literature was conducted to synthesize current knowledge regarding the interplay between glomerulonephritis and pregnancy. Results: The review underscores the centrality of the kidney in the context of pregnancy and highlights the role of glomerular disease, particularly when active. It emphasizes multifaceted risk modulators, including kidney function, hypertension, and proteinuria. Conclusion: Understanding the dynamics between pregnancy and glomerulonephritis is crucial for optimizing maternal and fetal outcomes. Preconception counseling and collaborative nephro-gynecological management emerge as pivotal components in addressing the unique challenges posed by this medical interplay.

Autoimmunity and Infection in Glomerular Disease.

The ongoing glomerular damage of infections is not limited to the most widely known form of post-streptococcal glomerulonephritis, which is today less common in the Western world; other forms of glomerulonephritis are associated with several bacterial, viral and parasitic pathogens. The mechanisms responsible range from the direct damage of glomerular cells to the formation and deposition of immunocomplexes to molecular mimicry to the secretion of superantigens. Similarly, in the course of glomerular disease, infections are more frequent than in the general population due to the loss of immunoglobulins in urine and the immunosuppressive agents used to treat the autoimmune disease that decrease the activity of the immune system. Recognizing this two-way link, understanding its pathogenetic mechanism, and identifying the most appropriate therapeutic choice are essential for the personalized management of patients. In this continuously developing field, this short review summarizes the current state of the art as support for physicians, who are increasingly involved in managing patients with glomerular disease and infections.

Potential Role of Copper in Diabetes and Diabetic Kidney Disease.

Copper is a fundamental element for the homeostasis of the body. It is the third most abundant essential transition metal in humans. Changes in the concentration of copper in the blood are responsible for numerous diseases affecting various organs, including the heart, brain, kidneys, and liver. Even small copper deficiencies can lead to the development and progression of several pathologies. On the other hand, excessive exposure to copper can cause toxicity in many human organs, leading to various systemic alterations. In the kidney, increased copper concentration in the blood can cause deposition of this element in the kidneys, leading to nephrotoxicity. One of the most interesting aspects of copper balance is its influence on diabetes and the progression of its complications, such as Diabetic Kidney Disease (DKD). Several studies have shown a close relationship between copper serum levels and altered glycemic control. An imbalance of copper can lead to the progression of diabetes-related complications and impaired antioxidant homeostasis. A high Zinc/Copper (Zn/Cu) ratio is associated with improved renal function and reduced risk of poor glycemic control in patients with type two diabetes mellitus (T2DM). Furthermore, the progression of DKD appears to be related to the extent of urinary copper excretion, while regulation of adequate serum copper concentration appears to prevent and treat DKD. The aim of this review is to evaluate the possible role of copper in DKD patients.

Role of Zinc in Diabetic Kidney Disease.

Diabetic Kidney Disease (DKD) represents the most common cause of Chronic Kidney Disease (CKD) in developed countries. Approximately 30% to 40% of diabetes mellitus (DM) subjects develop DKD, and its presence significantly increases the risk for morbidity and mortality. In this context, Zinc seems to have a potential role in kidney and body homeostasis in diabetic individuals as well as in patients at a high risk of developing this condition. This essential element has functions that may counteract diabetes-related risk factors and complications, which include stabilization of insulin hexamers and pancreatic insulin storage and improved glycemic control. In our review, we analyzed the current knowledge on the role of zinc in the management of renal impairment in course of DM. Several studies underline the critical role of zinc in reducing oxidative stress levels, which is considered the common denominator of the mechanisms responsible for the progression of kidney disease. Reaching and maintaining a proper serum zinc level could represent a valuable target to reduce symptoms related to DM complications and contrast the progression of kidney impairment in patients with the high risk of developing end-stage renal disease. In conclusion, analyzing the beneficial role of zinc in this review would advance our knowledge on the possible strategies of DM and DKD treatment.