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EJHaem Nov 2023
PubMed: 38024641
DOI: 10.1002/jha2.766 -
Biomedicine & Pharmacotherapy =... Dec 2023The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD)...
The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D-FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7-10 animals per group). After 6 weeks, D and D-FIN exhibited significantly elevated blood glucose levels (271.7 ± 67.1 mg/dl and 266.3 ± 46.8 mg/dl) as compared to C (110.3 ± 4.4 mg/dl; p < 0.05). D showed a 10-fold increase of kidney damage markers Kim-1 and Ngal which was significantly suppressed in D-FIN. Blood pressure, pulse wave velocity (PWV) and arterial collagen deposition were lower in D-FIN, associated to an improvement in endothelial function due to a reduction in pro-contractile prostaglandins, as well as reactive oxygen species (ROS) and inflammatory cytokines (IL-1, IL-6, TNFα and TGFβ) in perivascular and perirenal adipose tissue (PVAT and PRAT, respectively). In addition, FIN restored the imbalance observed in CKD between the procalcifying BMP-2 and the nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis.
Topics: Humans; Rats; Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Pulse Wave Analysis; Rats, Wistar; Kidney; Renal Insufficiency, Chronic
PubMed: 37832406
DOI: 10.1016/j.biopha.2023.115661 -
Heart International 2019Hypertension is a common health problem, which leads to a substantial mortality and morbidity burden, globally. The management of patients with high-risk and... (Review)
Review
Hypertension is a common health problem, which leads to a substantial mortality and morbidity burden, globally. The management of patients with high-risk and treatment-resistant hypertension remains a major clinical challenge to the treating physician. Renal denervation (RD) is an emerging technique, comprising modification of the renal sympathetic nerve supply which courses around the renal arteries. Endovascular access is obtained to the renal arteries, followed by delivery of heat energy to the peri-renal sympathetic nerves. This leads to the reduction of blood pressure with or without the addition of anti-hypertensive pharmacotherapy. Earlier trials led to clinical equipoise, but more recent trials (e.g. SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED and RADIANCE-HTN SOLO), which were designed to overcome the limitations of the initial studies, have provided support for the efficacy of RD in hypertension management. Evidence (from randomised, non-randomised, sham-controlled and non-sham-controlled trials) for the use of RD in the treatment of hypertension is reviewed in this article. Finally, the current clinical role, gaps in evidence, and the expected future evolution of RD are discussed.
PubMed: 36274824
DOI: 10.17925/HI.2019.13.2.12 -
Clinical Kidney Journal Jan 2024The prevalence of obesity has tripled over the past five decades. Obesity, especially visceral obesity, is closely related to hypertension, increasing the risk of... (Review)
Review
The prevalence of obesity has tripled over the past five decades. Obesity, especially visceral obesity, is closely related to hypertension, increasing the risk of primary (essential) hypertension by 65%-75%. Hypertension is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and its prevalence is rapidly increasing following the pandemic rise in obesity. Although the causal relationship between obesity and high blood pressure (BP) is well established, the detailed mechanisms for such association are still under research. For more than 30 years sympathetic nervous system (SNS) and kidney sodium reabsorption activation, secondary to insulin resistance and compensatory hyperinsulinemia, have been considered as primary mediators of elevated BP in obesity. However, experimental and clinical data show that severe insulin resistance and hyperinsulinemia can occur in the absence of elevated BP, challenging the causal relationship between insulin resistance and hyperinsulinemia as the key factor linking obesity to hypertension. The purpose of Part 1 of this review is to summarize the available data on recently emerging mechanisms believed to contribute to obesity-related hypertension through increased sodium reabsorption and volume expansion, such as: physical compression of the kidney by perirenal/intrarenal fat and overactivation of the systemic/renal SNS and the renin-angiotensin-aldosterone system. The role of hyperleptinemia, impaired chemoreceptor and baroreceptor reflexes, and increased perivascular fat is also discussed. Specifically targeting these mechanisms may pave the way for a new therapeutic intervention in the treatment of obesity-related hypertension in the context of 'precision medicine' principles, which will be discussed in Part 2.
PubMed: 38186879
DOI: 10.1093/ckj/sfad282 -
Urology Case Reports Jul 2022A real life-threatening emergency, Wunderlich syndrome (WS) is an interesting and unknown clinical condition characterised by intense beginning of spontaneous,...
A real life-threatening emergency, Wunderlich syndrome (WS) is an interesting and unknown clinical condition characterised by intense beginning of spontaneous, non-traumatic renal haemorrhage in the sub-capsular and perirenal space, with a typical clinical and radiological presentation [1] that allow the diagnosis. Although most cases are treated invasively either by surgery or embolization to control the bleeding, Fortunately our 66 year old patient admitted to the Mohammed V military hospital in Rabat benefited from a conservative treatment, which allowed him to avoid all the associated complications and to be discharged from hospital in less than 4 days.
PubMed: 35520030
DOI: 10.1016/j.eucr.2022.102093 -
Adipocyte Dec 2022Brown adipose tissue (BAT) generates heat through non-shivering thermogenesis, and increasing BAT amounts or activity could facilitate obesity treatment and provide...
Brown adipose tissue (BAT) generates heat through non-shivering thermogenesis, and increasing BAT amounts or activity could facilitate obesity treatment and provide metabolic benefits. In mice, BAT has been reported in perirenal, thoracic and cranial sites. Here, we describe new pelvic and lower abdominal BAT depots located around the urethra, internal reproductive and urinary tract organs and major lower pelvic blood vessels, as well as between adjacent muscles where the upper hind leg meets the abdominal cavity. Immunohistochemical, western blot and PCR analyses revealed that these tissues expressed BAT markers such as uncoupling protein 1 (UCP1) and CIDEA, but not white adipose markers, and β3-adrenergic stimulation increased UCP1 amounts, a classic characteristic of BAT tissue. The newly identified BAT stores contained extensive sympathetic innervation with high mitochondrial density and multilocular lipid droplets similar to interscapular BAT. BAT repositories were present and functional neonatally, and showed developmental changes between the neonatal and adult periods. In summary, several new depots showing classical BAT characteristics are reported and characterized in the lower abdominal/pelvic region of mice. These BAT stores are likely significant metabolic regulators in the mouse and some data suggests that similar BAT depots may also exist in humans.
Topics: Animals; Mice; Adipose Tissue, Brown; Adrenergic Agents; Pelvis; Thermogenesis; Uncoupling Protein 1
PubMed: 36260113
DOI: 10.1080/21623945.2022.2133415 -
Cureus Jan 2022Background The incidence and consequences of the perirenal extravasation of the irrigation fluid during retrograde intrarenal surgery (RIRS) are not fully elucidated....
Background The incidence and consequences of the perirenal extravasation of the irrigation fluid during retrograde intrarenal surgery (RIRS) are not fully elucidated. The objective of this study was to assess the incidence, risk factors, and complications of perirenal extravasation of irrigation fluid during RIRS. Methods This prospective observational study was conducted in the Department of Urology, Bir Hospital, Kathmandu, Nepal, from January 2020 to March 2021. Patients undergoing RIRS for renal stones less than 2 cm in diameter were included in the study. Irrigation during the procedure was performed using isotonic normal saline under gravity at 50 cm from the symphysis pubis of patients with intermittent manual compression if required. Lithotripsy was performed with 120-Watt Ho:YAG laser using 200-micron laser fiber. Retrograde pyelogram was performed after the completion of lithotripsy to document the presence or absence of extravasation on fluoroscopic images. A double-J stent was placed at the end in all patients. Patients were observed for systemic inflammatory response syndrome (SIRS) features. Postoperative abdominal ultrasonography was performed on the first postoperative day to assess the perirenal collection together with complete blood count. The visual analogue scale (VAS) was used to assess pain in postoperative period. The preoperative patient's and stone characteristics, hydronephrosis, intraoperative characteristics, and postoperative findings were analyzed. Results A total of 71 patients who underwent RIRS during the study period were analyzed. The mean (SD) stone size was 13.19 (3.12) mm. Intraoperative perirenal extravasation of contrast was noted in eight (11.26%) patients; however, no patient had ipsilateral perirenal collection on ultrasonography obtained on the first postoperative day. No significant differences were observed among patients with or without perirenal extravasation in terms of mean stone size, laser settings, operative duration, and lasing duration. Use of ureteral access sheath (UAS) was associated with lower incidence of extravasation; however, it was not significant. SIRS was documented in eight patients overall, with none of the patients with extravasation having features of SIRS. Patients with extravasation experienced more postoperative flank pain (p<0.05). Conclusion Perirenal extravasation was common during RIRS and was associated with higher postoperative pain scores. Stone size, use of UAS, laser settings, operative duration, and lasing duration were not associated with an increased risk of extravasation. Extravasation was not associated with increased postoperative complications.
PubMed: 35186546
DOI: 10.7759/cureus.21283 -
Radiology Case Reports Jul 2024Renal cell carcinoma (RCC) is an extremely rare cancer in pediatric, accounting for 0.1% to 0.3% of all pediatric malignancies. Due to its low incidence in this age...
Renal cell carcinoma (RCC) is an extremely rare cancer in pediatric, accounting for 0.1% to 0.3% of all pediatric malignancies. Due to its low incidence in this age group, literature on pediatric RCC is limited. We present a case of localized RCC in pediatric patient treated with nephroureterectomy and lymphadenectomy. A 14-year-old girl with a 2-year history of red urine, blood clots, and left flank pain underwent physical examination, revealing left flank tenderness. Laboratory results showed anemia, leukocytosis, elevated LDH, and erythrocytes in urine. Imaging revealed a hyperechoic area in the left kidney's lower pole (4.0 × 2.8 cm). Contrast abdominal CT scan indicated a solid mass (5.4 × 3.8 × 3.2 cm) in left renal pelvis extending to the minor calyx and severe hydronephrosis. The patient was diagnosed with suspected cT3N0M0 left upper tract urothelial carcinoma and underwent cystoscopy, bladder cuff excision, and left radical nephroureterectomy with paraaortic lymph node dissection. Pathological analysis revealed clear cell type renal cell carcinoma, WHO ISUP grade IV, extending to the perirenal fat, with tumor-free ureteral resection margins, and no paraaortic lymph node metastasis. Follow-up on postoperative period showed a satisfactory outcome. In cases of pediatric localized RCC, surgical therapy, including radical nephrectomy or nephron-sparing surgery (NSS), can be a preferred treatment for small tumor volumes. This approach preserves kidney function and is generally considered safe for achieving tumor-free margins.
PubMed: 38721391
DOI: 10.1016/j.radcr.2024.03.022 -
Animals : An Open Access Journal From... Jun 2023The objective of this study was to determine the effects of exogenous glucocorticoid administration on leptin concentrations and brain development markers, such as...
The objective of this study was to determine the effects of exogenous glucocorticoid administration on leptin concentrations and brain development markers, such as protein and hypothalamic gene expression, in dairy bull calves. Within 4 h of parturition, Holstein bulls were intravenously infused with either a low cortisol dose (LC; = 9, 3.5 µg/kg of body weight (BW)), high cortisol dose (HC; = 9, 7.0 µg/kg BW), or control (CON; = 9, saline) dose, with a 2nd infusion 24 h postpartum. Jugular blood was collected prior to infusion and daily until the calves were euthanized (day 5). Cerebrospinal fluid (CSF) from the third ventricle and adipose (omental, perirenal, and mesenteric) and hypothalamic tissue were collected. The blood and CSF samples were analyzed for leptin concentrations. The data were analyzed using SAS. Serum ( = 0.013) and CSF ( = 0.005) leptin concentrations in HC- and LC-treated calves were decreased compared with CON-treated calves. Leptin protein expression was decreased ( < 0.044) in perirenal and omental adipose tissue of LC-treated calves compared with CON-treated calves. Gene abundance of brain-derived neurotrophic factor and fibroblast growth factors 1 and 2 were decreased ( < 0.006) in HC- and LC-treated calves compared with CON-treated calves. In summary, cortisol administered to dairy bull calves reduced leptin concentrations, decreased leptin protein expression in perirenal and omental adipose tissue, and altered gene expression in hypothalamic tissue.
PubMed: 37370490
DOI: 10.3390/ani13121980 -
Physiology & Behavior Oct 2019Glucocorticoids (GC) increase food intake and body weight in humans and rodents and chronic stress and GC treatment-induced enhancement of the plasma concentration of GC...
Glucocorticoids (GC) increase food intake and body weight in humans and rodents and chronic stress and GC treatment-induced enhancement of the plasma concentration of GC lead to obesity and metabolic changes. In response to hypercaloric treatment, males were shown to be more susceptible to obesity than females, demonstrating that sex differences may affect energy homeostasis. The objective of the current study was to evaluate the effects of prolonged (28 days) treatment with dexamethasone or corticosterone on food intake and body weight gain in intact rats, both male and female. Also examined were Lee index, weights and area of adipocytes of retroperitoneal and perigonadal+perirenal adipose tissues, glucose tolerance test (GTT) and plasma concentrations of free fatty acids, cholesterol and triglycerides. Treatment with dexamethasone was able to increase body weight, food intake, area of adipocytes and weight of retroperitoneal adipose tissue in males. Prolonged treatment with corticosterone also stimulated body weight gain and food intake in males. In addition, it induced an increase in the area of adipocytes and weight of perirenal+perigonadal adipose tissue and higher glycemia after GTT in these animals, without changes on Lee index and plasma parameters after both GC treatments. No parameter was changed by dexamethasone or corticosterone treatment in female rats. Thus, it can be concluded that male rats are more susceptible to the anabolic effects of glucocorticoids than female rats, and these responses can be due to the protective effects of circulating estrogens in females, and/or the difference between males and females in the expression/activity of corticosteroids receptors.
Topics: Adipocytes; Adipose Tissue; Adipose Tissue, White; Anabolic Agents; Animals; Corticosterone; Dexamethasone; Eating; Female; Glucocorticoids; Glucose Tolerance Test; Lipids; Male; Rats; Rats, Wistar; Sex Characteristics; Weight Gain
PubMed: 31247241
DOI: 10.1016/j.physbeh.2019.112587