Kidney International Supplements最新文献

Over the past 30 years there have been many complementary therapies developed to achieve glycemic control and have an impact on cardiovascular outcomes, as well as reduce the risk of microvascular disease. The 2 most notable new entries have been the sodium–glucose cotransporter 2 (SGLT2) inhibitors and the glucagon-like peptide-1 (GLP-1) agonists. Both these classes of agents have demonstrated reductions in cardiovascular event rates as well as reductions in blood pressure and weight. Moreover, while both have demonstrated a benefit in slowing nephropathy progression, the SGLT2 inhibitors appear to have a significantly greater effect compared with the GLP-1 agents. There is an ongoing trial specifically powered for renal disease progression, CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy). Additionally, there are 2 other classes of agents being tested to slow nephropathy progression, a selective endothelin-1 receptor antagonist, atrasantan, in the SONAR (Study of Diabetic Nephropathy With Atrasentan) trial and a nonsteroidal mineralocorticoid receptor antagonist, finerenone, in the FIDELIO (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus) trial. These and other studies are discussed.

Approximately 20% to 40% of patients with type 1 or type 2 diabetes mellitus develop diabetic kidney disease. This is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h, or > 300 mg/g creatinine), a relentless decline in glomerular filtration rate (GFR), raised arterial blood pressure, and enhanced cardiovascular morbidity and mortality. There is a characteristic histopathology. In classical diabetic nephropathy, the first clinical sign is moderately increased urine albumin excretion (microalbuminuria: 30–300 mg/24 h, or 30–300 mg/g creatinine; albuminuria grade A2). Untreated microalbuminuria will gradually worsen, reaching clinical proteinuria or severely increased albuminuria (albuminuria grade A3) over 5 to 15 years. The GFR then begins to decline, and without treatment, end-stage renal failure is likely to result in 5 to 7 years. Although albuminuria is the first sign of diabetic nephropathy, the first symptom is usually peripheral edema, which occurs at a very late stage. Regular, systematic screening for diabetic kidney disease is needed in order to identify patients at risk of or with presymptomatic diabetic kidney disease. Annual monitoring of urinary albumin-to-creatinine ratio, estimated GFR, and blood pressure is recommended. Several new biomarkers or profiles of biomarkers have been investigated to improve prognostic and diagnostic precision, but none have yet been implemented in routine clinical care. In the future such techniques may pave the way for personalized treatment.

Anemia is a common complication of chronic kidney disease. Use of erythropoiesis-stimulating agents (ESA) has been a mainstay of treatment since 1990. A series of large trials demonstrated that ESAs have serious safety problems, including increasing cardiovascular and thrombotic events, and death. Analyses suggest high pharmacologic doses of ESAs, rather than the highly achieved hemoglobin, may mediate harm. Hypoxia-inducible factor (HIF) activators stimulate endogenous erythropoietin production and enhance iron availability. In early clinical trials, these oral agents appear to be capable of replacing ESA therapy and minimizing the need for i.v. iron therapy for chronic kidney disease–related anemia, while having other potentially advantageous actions. Large phase 3 trials are underway with several HIF activators. This commentary reviews trends in anemia management, the safety issues related to our present therapies, the role of HIF in regulating erythropoiesis, and the diverse actions of HIF activators.

Hyperkalemia is a frequently detected electrolyte abnormality that can cause life-threatening complications. Hyperkalemia is most often the result of intrinsic (decreased glomerular filtration rate; selective reduction in distal tubule secretory function; impaired mineralocorticoid activity; and metabolic disturbances, such as acidemia and hyperglycemia) and extrinsic factors (e.g., drugs, such as renin-angiotensin-aldosterone system inhibitors, and potassium intake). The frequent use of renin-angiotensin-aldosterone system inhibitors in patients who are already susceptible to hyperkalemia (e.g., patients with chronic kidney disease, diabetes mellitus, or congestive heart failure) contributes to the high incidence of hyperkalemia. There is a need to understand the causes of hyperkalemia and to be aware of strategies addressing the disorder in a way that provides the most optimal outcome for affected patients. The recent development of 2 new oral potassium-binding agents has led to the emergence of a new paradigm in the treatment of hyperkalemia.