ANTONIO CARLOS SEGURO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina - Líder
4 resultados
Resultados de Busca
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- Paracrine and endocrine regulation of renal K+ secretion(2022) POLIDORO, Juliano Z.; LUCHI, Weverton M.; SEGURO, Antonio Carlos; MALNIC, Gerhard; GIRARDI, Adriana C. C.The seminal studies conducted by Giebisch and coworkers in the 1960s paved the way for understanding the renal mechanisms involved in K+ homeostasis. It was demonstrated that differential handling of K+ in the distal segments of the nephron is crucial for proper K+ balance. Although aldosterone had been classically ascribed as the major ion transport regulator in the distal nephron, thereby contributing to K+ homeostasis, it became clear that aldosterone per se could not explain the ability of the kidney to modulate kaliuresis in both acute and chronic settings. The existence of alternative kaliuretic and antikaliuretic mechanisms was suggested by physiological studies in the 1980s but only gained form and shape with the advent of molecular biology. It is now established that the kidneys recruit several endocrine and paracrine mechanisms for adequate kaliuretic response. These mechanisms include the direct effects of peritubular K+, a gut-kidney regulatory axis sensing dietary K+ levels, the kidney secretion of kallikrein during postprandial periods, the upregulation of angiotensin II receptors in the distal nephron during chronic changes in K+ diet, and the local increase of prostaglandins by low-K(+ )diet. This review discusses recent advances in the understanding of endocrine and paracrine mechanisms underlying the modulation of K+ secretion and how these mechanisms impact kaliuresis and K+ balance. We also highlight important unknowns about the regulation of renal K+ excretion under physiological circumstances.
- Administration of a single dose of lithium ameliorates rhabdomyolysis-associated acute kidney injury in rats(2023) SHIMIZU, Maria Heloisa Massola; VOLPINI, Rildo Aparecido; BRAGANCA, Ana Carolina de; NASCIMENTO, Mariana Moura; BERNARDO, Desiree Rita Denelle; SEGURO, Antonio Carlos; CANALE, DanieleRhabdomyolysis is characterized by muscle damage and leads to acute kidney injury (AKI). Clinical and experimental studies suggest that glycogen synthase kinase 3 beta (GSK3 beta) inhibition protects against AKI basically through its critical role in tubular epithelial cell apoptosis, inflammation and fibrosis. Treatment with a single dose of lithium, an inhibitor of GSK3 beta, accelerated recovery of renal function in cisplatin and ischemic/reperfusion-induced AKI models. We aimed to evaluate the efficacy of a single dose of lithium in the treatment of rhabdomyolysis-induced AKI. Male Wistar rats were allocated to four groups: Sham, received saline 0.9% intraperitoneally (IP); lithium (Li), received a single IP injection of lithium chloride (LiCl) 80 mg/kg body weight (BW); glycerol (Gly), received a single dose of glycerol 50% 5 mL/kg BW intramuscular (IM); glycerol plus lithium (Gly+Li), received a single dose of glycerol 50% IM plus LiCl IP injected 2 hours after glycerol administration. After 24 hours, we performed inulin clearance experiments and collected blood / kidney / muscle samples. Gly rats exhibited renal function impairment accompanied by kidney injury, inflammation and alterations in signaling pathways for apoptosis and redox state balance. Gly+Li rats showed a remarkable improvement in renal function as well as kidney injury score, diminished CPK levels and an overstated decrease of renal and muscle GSK3 beta protein expression. Furthermore, administration of lithium lowered the amount of macrophage infiltrate, reduced NF kappa B and caspase renal protein expression and increased the antioxidant component MnSOD. Lithium treatment attenuated renal dysfunction in rhabdomyolysis-associated AKI by improving inulin clearance and reducing CPK levels, inflammation, apoptosis and oxidative stress. These therapeutic effects were due to the inhibition of GSK3 beta and possibly associated with a decrease in muscle injury.
- The association between obesity and vitamin D deficiency modifies the progression of kidney disease after ischemia/reperfusion injury(2022) BERNARDO, Desiree Rita Denelle; CANALE, Daniele; NASCIMENTO, Mariana Moura; SHIMIZU, Maria Heloisa Massola; SEGURO, Antonio Carlos; BRAGANCA, Ana Carolina de; VOLPINI, Rildo AparecidoAcute kidney injury (AKI) alters renal hemodynamics, leading to tubular injury, activating pathways of inflammation, proliferation, and cell death. The initial damage caused to renal tissue after an ischemia/reperfusion (I/R) injury exerts an important role in the pathogenesis of the course of AKI, as well as in the predisposition to chronic kidney disease. Vitamin D deficiency has been considered a risk factor for kidney disease and it is associated with tubulointerstitial damage, contributing to the progression of kidney disease. Obesity is directly related to diabetes mellitus and hypertension, the main metabolic disorders responsible for the progression of kidney disease. Furthermore, the expansion of adipose tissue is described as an important factor for increased secretion of pro-inflammatory cytokines and their respective influence on the progression of kidney disease. We aimed to investigate the influence of vitamin D deficiency and obesity on the progression of renal disease in a murine model of renal I/R. Male Wistar rats underwent renal I/R surgery on day 45 and followed until day 90 of the protocol. We allocated the animals to four groups according to each diet received: standard (SD), vitamin D-depleted (VDD), high fat (HFD), or high fat vitamin D-depleted (HFDV). At the end of 90 days, we observed almost undetectable levels of vitamin D in the VDD and HFDV groups. In addition, HFD and HFDV groups presented alterations in the anthropometric and metabolic profile. The combination of vitamin D deficiency and obesity contributed to alterations of functional and hemodynamic parameters observed in the HFDV group. Moreover, this combination favored the exacerbation of the inflammatory process and the renal expression of extracellular matrix proteins and phenotypic alteration markers, resulting in an enlargement of the tubulointerstitial compartment. All these changes were associated with an increased renal expression of transforming growth factor beta and reduced expression of the vitamin D receptor. Our results show that the synergistic effect of obesity and vitamin D deficiency exacerbated the hemodynamic and morphological changes present in the evolution of renal disease induced by I/R.
- Is It Time for a Requiem for Creatine Supplementation-Induced Kidney Failure? A Narrative Review(2023) LONGOBARDI, Igor; GUALANO, Bruno; SEGURO, Antonio Carlos; ROSCHEL, HamiltonCreatine has become one of the most popular dietary supplements among a wide range of healthy and clinical populations. However, its potential adverse effects on kidney health are still a matter of concern. This is a narrative review of the effects of creatine supplementation on kidney function. Despite a few case reports and animal studies suggesting that creatine may impair kidney function, clinical trials with controlled designs do not support this claim. Creatine supplementation may increase serum creatinine (Crn) concentration for some individuals, but it does not necessarily indicate kidney dysfunction, as creatine is spontaneously converted into Crn. Based on studies assessing kidney function using reliable methods, creatine supplements have been shown to be safe for human consumption. Further studies with people who have pre-existing kidney disease remain necessary.