Advances in chronic kidney disease最新文献

Over the past 2 decades, significant research and advancements have been made in oncology and its therapeutics. Thanks to novel diagnostic methods, treatments, and supportive measures, patients with cancer live longer and have a better quality of life. However, an unforeseen consequence of this progress has been increasing medical complications, including acute kidney injury. The purpose of this review is to provide an overview of the epidemiology and most common causes of acute kidney injury in patients with cancer unrelated to oncological treatment.

Tumor lysis syndrome (TLS) is an oncologic emergency due to massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation. Clinical presentation is characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia. Acute kidney injury due to tumor lysis is potentiated by the precipitation of uric acid and calcium phosphate as well as renal vasoconstriction. Early recognition of tumor lysis can help prevent cardiac arrhythmias, seizures, and death. Management includes intravenous hydration to maintain urine flow, medications targeting hyperuricemia including rasburicase and allopurinol and in severe cases renal replacement therapy may be required.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective in reducing glycemia in patients with type 2 diabetes (T2D). These medications effectively reduce cardiovascular (CV) risk in patients with T2D and established CV disease or with multiple risk factors. In addition, treatment with GLP-1 RA may exert protective effects on the diabetic kidney. Herein, we summarize the findings regarding the kidney safety and efficacy of GLP-1 RAs in patients with T2D. We review data from GLP-1 RAs phase 3 kidney studies, CV outcome trials, as well as real-world evidence. The accumulating data show that treatment with GLP-1 RAs is safe, well-tolerated, and effective in patients with different levels of kidney dysfunction. Furthermore, CV outcome trials suggest that GLP-1 RAs reduce albuminuria and may attenuate the decline in kidney function over time. The ongoing FLOW trial studying the effects of semaglutide in patients with diabetic kidney disease is expected to shed light on the effects of GLP-1 RAs on kidney outcomes and clarify their role in the management of patients with T2D and kidney disease.

Large-scale randomized trials have demonstrated the remarkable capacity of sodium-glucose cotransporter 2 inhibitors to reduce the risk of cardiovascular outcomes and kidney disease progression, irrespective of the presence or absence of type 2 diabetes mellitus. Although the results of these trials have transformed clinical practice guidelines, the mechanisms underpinning the wide-ranging benefits of this class of agents remain incompletely understood and subject to ongoing investigation. Improvements in cardiometabolic risk factors such as glucose, blood pressure, body weight, and albuminuria likely contribute. However, other direct effects on physiological and cellular function, such as restoration of tubuloglomerular feedback, improvements in kidney and cardiac oxygenation and energy efficiency, as well as restoration of normal autophagy are also likely to be important. This review summarizes the rationale and potential mechanisms for cardiorenal protection with sodium-glucose cotransporter 2 inhibitors in people with and without diabetes, their relative importance, and the experimental and clinical lines of evidence supporting these hypotheses.

Chronic low-grade inflammation, now coined by the new paradigm as “metaflammation” or “metainflammation”, has been linked to chronic kidney disease and its progression. In diabetes, altered metabolism denotes factors associated with the metabolic syndrome and hyperglycemia, among others. The interplay among hyperglycemia, oxidative stress, and inflammation in the pathogenesis of diabetic kidney disease (DKD) has been broadly explored. Identification of mediators of inflammatory processes involving macrophage infiltration, production of inflammasomes, release of cytokines, and activation of pertinent signaling pathways including mitogen-activated protein kinase, Jun N-terminal kinase, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway (JAK/STAT), and apoptosis signal-regulating kinase 1 signaling mechanisms have enabled the development of therapeutic agents for DKD. This review describes the evidence supporting the contribution of the inflammatory response and fibrotic changes and focuses on selected, novel, promising drugs as well as repurposed drugs that have made it to phase 2, 3, or 4 of clinical trials in adults with type 2 diabetes mellitus and their potential to become an important part of our armamentarium to improve the management of DKD. Importantly, drugs that solely target inflammatory processes may be insufficient to fully optimize care of patients with DKD because of the complex nature of the disease.

The area of aldosterone blockade has exploded in the last decade with the development of four new compounds of a different class referred to as nonsteroidal mineralocorticoid receptor antagonists (MRAs). Their chemistry and clinical charatcteristics are distinctly different from their steroidal cousins. Apart from blocking aldosterone activity, albeit in a different way than the steroidal MRAs, they have much less blood pressure (BP) effects and are better tolerated. The spectrum of nonsteroidal MRAs includes one agent with significant BP reduction, KBP-5074, to agents with minimal BP effects yet have demonstrated significant cardiorenal risk reduction in diabetic kidney disease, finerenone. The paper reviews the development and pharmacology of these different agents and tries to provide a perspective as to their place in the spectrum of aldosterone excess disorders.

Post-transplant diabetes mellitus is a frequent consequence of or a pre-existing comorbidity in solid organ transplantation (SOT) that is associated with greater morbidity and mortality. Novel glucose-lowering agents that have been shown to have cardiovascular morbidity/mortality benefit and renal protective effects such as sodium glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists are being incorporated into new standard of care for diabetes mellitus. There is a paucity of data regarding the use of these agents in SOT. In this article, we will aim to review available literature on newer glucose-lowering therapeutics in SOT, mainly sodium glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, their mechanism of action, benefits, risks, and safety profiles.

The pathobiology of diabetic kidney disease (DKD) involves an interplay between all the many different cell types that exist within the kidney and their shared and cumulative dysfunction in response to chronic hyperglycemia. DKD is characteriszed by morphological changes including tubular hypertrophy, podocyte dysfunction, mesangial expansion and mesangiolysis, endothelitis and capillary rarefaction, arteriolar hyalinosis, basement membrane thickening, and ultimately nephron dropout and tubulointerstitial fibrosis. These adaptive but ultimately maladaptive changes accelerate the progression of lesions in the diabetic kidney by increasing mechanical and oxidative stress, hypoxia, fibrogenesis, inflammation, senescence, and apoptosis. In particular, atrophy at the critical junction between Bowman's capsule and the proximal tubule likely represent the leading cause of nephron dropout and kidney function decline in DKD. Preventing, slowing, or reversing these changes should be the target of future “smart” therapies for patients with DKD, many of which are now under development.