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World Journal of Nephrology Jan 2023Obstructive uropathy is an important cause of acute and chronic kidney disease. Decompression of the urinary tract is an essential aspect of treatment. The cause and... (Review)
Review
Obstructive uropathy is an important cause of acute and chronic kidney disease. Decompression of the urinary tract is an essential aspect of treatment. The cause and aetiology of obstruction typically determine the surgical approach. Acute relief of obstruction is frequently complicated by fluid and electrolyte imbalance. Standard therapeutic interventions for acute or chronic renal failure also apply for cases of obstructive uropathy. This narrative review summarises the early and long-term medical management of obstructive uropathy.
PubMed: 36704657
DOI: 10.5527/wjn.v12.i1.1 -
International Journal of Molecular... May 2021At the onset of diabetes, the kidney grows large and the glomerular filtration rate becomes abnormally high. These structural and hemodynamics changes affect kidney... (Review)
Review
At the onset of diabetes, the kidney grows large and the glomerular filtration rate becomes abnormally high. These structural and hemodynamics changes affect kidney function and may contribute to the development of chronic kidney disease. The goal of this study is to analyze how kidney function is altered in patients with diabetes and the renal effects of an anti-hyperglyceamic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules. To accomplish that goal, we have developed a computational model of kidney function in a patient with diabetes and conducted simulations to study the effects of diabetes and SGLT2 inhibition on solute and water transport along the nephrons. Simulation results indicate that diabetes-induced hyperfiltration and tubular hypertrophy enhances Na transport, especially along the proximal tubules and thick ascending limbs. These simulations suggest that SGLT2 inhibition may attenuate glomerular hyperfiltration by limiting Na-glucose transport, raising luminal [Cl] at the macula densa, restoring the tubuloglomerular feedback signal, thereby reducing single-nephron glomerular filtration rate.
Topics: Animals; Biological Transport; Biomarkers; Diabetes Mellitus; Diabetic Nephropathies; Disease Susceptibility; Humans; Kidney; Kidney Function Tests; Kidney Glomerulus; Kidney Tubules; Models, Biological; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 34072329
DOI: 10.3390/ijms22115819 -
International Journal of Nephrology and... 2019Glomerular filtration rate (GFR) and proteinuria-albuminuria are the renal functional parameters currently used to evaluate chronic kidney disease (CKD) severity.... (Review)
Review
Glomerular filtration rate (GFR) and proteinuria-albuminuria are the renal functional parameters currently used to evaluate chronic kidney disease (CKD) severity. However, tubular secretion is another important renal functional parameter to be taken into account since proximal tubule (PT) secretion, in particular, is a crucial renal mechanism for endogenous organic cations, anions and drug elimination. The residual diuresis is a relevant survival predictor in patients on dialysis, since their urine is produced by the glomerular and tubular functions. It has been hypothesized that drugs which up-regulate some renal tubular transporters could contribute to uremic toxin excretion, and nephroprevention. However, if tubular transporters' down-regulation observed in CKD patients and experimental models is a PT adaptation to avoid intracellular accumulation and damage from uremic toxins, consequently the increase of toxin removal by inducing tubular transporters' up-regulation could be deleterious to the kidney. Therefore, a deeper understanding of this phenomenon is currently needed. In conclusion, tubular function has an important role for endogenous organic cations, anions and drug excretion in CKD patients, and a deeper understanding of its multiple mechanisms could provide new therapeutic alternatives in this population.
PubMed: 31849512
DOI: 10.2147/IJNRD.S216673 -
JACC. Heart Failure Aug 2021Diabetes promotes the development of both heart failure with a reduced ejection fraction and heart failure with a preserved ejection fraction through diverse mechanisms,... (Review)
Review
Diabetes promotes the development of both heart failure with a reduced ejection fraction and heart failure with a preserved ejection fraction through diverse mechanisms, which are likely mediated through hyperinsulinemia rather than hyperglycemia. Diabetes promotes nutrient surplus signaling (through Akt and mammalian target of rapamycin complex 1) and inhibits nutrient deprivation signaling (through sirtuin-1 and its downstream effectors); this suppresses autophagy and promotes endoplasmic reticulum and oxidative stress and mitochondrial dysfunction, thereby undermining the health of diabetic cardiomyocytes. The hyperinsulinemia of diabetes may also activate sodium-hydrogen exchangers in cardiomyocytes (leading to injury and loss) and in the proximal renal tubules (leading to sodium retention). Diabetes may cause epicardial adipose tissue expansion, and the resulting secretion of proinflammatory adipocytokines onto the adjoining myocardium can lead to coronary microcirculatory dysfunction and myocardial inflammation and fibrosis. Interestingly, sodium-glucose cotransporter 2 (SGLT2) inhibitors-the only class of antidiabetic medication that reduces serious heart failure events-may act to mitigate each of these mechanisms. SGLT2 inhibitors up-regulate sirtuin-1 and its downstream effectors and autophagic flux, thus explaining the actions of these drugs to reduce oxidative stress, normalize mitochondrial structure and function, and mute proinflammatory pathways in the stressed myocardium. Inhibition of SGLT2 may also lead to a reduction in the activity of sodium-hydrogen exchangers in the kidney (leading to diuresis) and in the heart (attenuating the development of cardiac hypertrophy and systolic dysfunction). Finally, SGLT2 inhibitors reduce the mass and mute the adverse biology of epicardial adipose tissue (and reduce the secretion of leptin), thus explaining the capacity of these drugs to mitigate myocardial inflammation, microcirculatory dysfunction, and fibrosis, and improve ventricular filling dynamics. The pathophysiological mechanisms by which SGLT2 inhibitors may benefit heart failure likely differ depending on ejection fraction, but each represents interference with distinct pathways by which hyperinsulinemia may adversely affect cardiac structure and function.
Topics: Diabetes Mellitus; Heart Failure; Humans; Microcirculation; Myocytes, Cardiac; Stroke Volume
PubMed: 34325884
DOI: 10.1016/j.jchf.2021.05.019 -
Kidney360 Jun 2022
Topics: Creatinine; Glomerular Filtration Rate; Kidney Function Tests
PubMed: 35845325
DOI: 10.34067/KID.0002302022 -
Cardiovascular Diabetology May 2020Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal...
BACKGROUND
Glucagon-like peptide-1 (GLP-1) induces diuresis and natriuresis. Previously we have shown that GLP-1 activates afferent renal nerve to increase efferent renal sympathetic nerve activity that negates the diuresis and natriuresis as a negative feedback mechanism in normal rats. However, renal effects of GLP-1 in heart failure (HF) has not been elucidated. The present study was designed to assess GLP-1-induced diuresis and natriuresis in rats with HF and its interactions with renal nerve activity.
METHODS
HF was induced in rats by coronary artery ligation. The direct recording of afferent renal nerve activity (ARNA) with intrapelvic injection of GLP-1 and total renal sympathetic nerve activity (RSNA) with intravenous infusion of GLP-1 were performed. GLP-1 receptor expression in renal pelvis, densely innervated by afferent renal nerve, was assessed by real-time PCR and western blot analysis. In separate group of rats after coronary artery ligation selective afferent renal denervation (A-RDN) was performed by periaxonal application of capsaicin, then intravenous infusion of GLP-1-induced diuresis and natriuresis were evaluated.
RESULTS
In HF, compared to sham-operated control; (1) response of increase in ARNA to intrapelvic injection of GLP-1 was enhanced (3.7 ± 0.4 vs. 2.0 ± 0.4 µV s), (2) GLP-1 receptor expression was increased in renal pelvis, (3) response of increase in RSNA to intravenous infusion of GLP-1 was enhanced (132 ± 30% vs. 70 ± 16% of the baseline level), and (4) diuretic and natriuretic responses to intravenous infusion of GLP-1 were blunted (urine flow 53.4 ± 4.3 vs. 78.6 ± 4.4 µl/min/gkw, sodium excretion 7.4 ± 0.8 vs. 10.9 ± 1.0 µEq/min/gkw). A-RDN induced significant increases in diuretic and natriuretic responses to GLP-1 in HF (urine flow 96.0 ± 1.9 vs. 53.4 ± 4.3 µl/min/gkw, sodium excretion 13.6 ± 1.4 vs. 7.4 ± 0.8 µEq/min/gkw).
CONCLUSIONS
The excessive activation of neural circuitry involving afferent and efferent renal nerves suppresses diuretic and natriuretic responses to GLP-1 in HF. These pathophysiological responses to GLP-1 might be involved in the interaction between incretin-based medicines and established HF condition. RDN restores diuretic and natriuretic effects of GLP-1 and thus has potential beneficial therapeutic implication for diabetic HF patients.
Topics: Animals; Capsaicin; Disease Models, Animal; Diuresis; Diuretics; Glucagon-Like Peptide 1; Heart Failure; Infusions, Intravenous; Kidney; Male; Natriuresis; Rats, Sprague-Dawley; Sympathectomy, Chemical
PubMed: 32384887
DOI: 10.1186/s12933-020-01029-0 -
Journal of Clinical Medicine Mar 2024Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive... (Review)
Review
Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician's experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio-renal interactions, and HF phenotypes.
PubMed: 38541899
DOI: 10.3390/jcm13061674 -
Lakartidningen Jun 2020Right-sided heart failure is a common disease that leads to increased morbidity and mortality. Despite this it is ill understood. Echocardiography is currently the...
Right-sided heart failure is a common disease that leads to increased morbidity and mortality. Despite this it is ill understood. Echocardiography is currently the primary mode for diagnosis and tricuspid annular plane systolic excursion and fractional area change are good measurements to use for assessment. Volume management is central in treatment of both acute and chronic right-sided heart failure. In acute failure achieving effective diuresis is often more important than the addition of fluids. In the treatment of chronic heart failure, no strong evidence supports the use of RAAS-blockers, beta-blockers, aldosterone antagonists or digoxin. In the case of right-sided heart failure caused by pulmonary arterial hypertension vasodilator therapy may be of use, but not in cases of other forms of pulmonary hypertension.
Topics: Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 32542616
DOI: No ID Found -
Heliyon Dec 2023Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the...
BACKGROUND
Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the world including Asia, Tropical Africa, Western Gulf and Mediterranean countries. It has nutritional value, containing 4 % lipids, 23 % proteins, 28 % carbohydrates, 4 % fibers, vitamin E and several minerals. Traditionally, this plant has been used by several communities for pain, different inflammatory and kidney disorders. Ethno-botanical studies have reported the use of in nephrolithiasis kidney disorders and induction of diuresis, which requires a detailed pharmacological study to validate the folkloric use of as diuretic.
METHODS
The 70 % methanolic (Lp.Cr) extract was prepared and qualitatively checked for the presence of various phytochemicals. Phenolic, flavonoid, tannin and saponin contents were quantified. GC-MS analysis of Lp.Cr was also performed. Antioxidant potential of Lp.Cr was evaluated by DPPH, ABTS and nitrite radical scavenging assays. CUPRAC and FRAP assay described the reducing potential of Lp.Cr. Diuretic activity was performed in both acute and prolonged models at different doses followed by the estimation of electrolytes, urea and creatinine levels. The mechanism of diuresis was described by pre-treatment with atropine, l-NAME, indomethacin and carbonic anhydrase inhibition.
RESULTS
Lp.Cr. indicated high phenolic and flavonoid contents which correlated with good antioxidant activity. GC-MS analysis showed the presence of 104 compounds from different phytochemical classes. Diuretic activity was performed at 10-300 mg/kg concentrations where the dose of 100 and 300 mg/kg showed good diuretic and saluretic activity comparable to furosemide. Lp.Cr exhibited diuresis both in acute and prolonged study protocols which can be attributed to carbonic anhydrase inhibition, effect on prostaglandins and cholinergic pathways.
CONCLUSION
contained several phytochemicals and exhibited good antioxidant activity. It induced diuresis and saluretic activity which was comparable to furosemide at higher doses. Diuretic activity can be attributed to carbonic anhydrase inhibition, prostaglandin synthesis and cholinergic pathways.
PubMed: 38076186
DOI: 10.1016/j.heliyon.2023.e22485 -
Expert Review of Cardiovascular Therapy Jan 2022Torsemide is a loop diuretic that inhibits the Na+/K+/2Cl- cotransporter type 2 in the thick ascending loop of Henle, leading to increased excretion of urinary sodium... (Review)
Review
INTRODUCTION
Torsemide is a loop diuretic that inhibits the Na+/K+/2Cl- cotransporter type 2 in the thick ascending loop of Henle, leading to increased excretion of urinary sodium and chloride and associated diuresis. While furosemide remains the dominant diuretic utilized in current practice, increasing evidence supports potential advantages of torsemide in heart failure (HF) and/or renal disease.
AREAS COVERED
This narrative review covers the evidence for use of torsemide in HF and renal disease. Comparative effectiveness with regards to clinical outcomes is reviewed, as well as the ongoing multicenter trial, TRANSFORM-HF, comparing the effect of torsemide versus furosemide among patients with HF.
EXPERT OPINION
Compared with furosemide, torsemide has favorable pharmacodynamics/pharmacokinetics including higher bioavailability, longer duration of effect, minor renal excretion, decreased kaliuresis, and enhanced natriuresis/diuresis. These properties may be further supported by differential effects on RAAS regulation and fibrosis modulation as compared with other diuretics. The limited current body of evidence indicates that torsemide may be superior to furosemide with respect to improving HF functional status and reducing HF hospitalization, and there are mixed data regarding effect on reducing overall cardiovascular hospitalizations/mortality. Further, randomized data are necessary to definitively determine if torsemide can reduce risk of mortality and hospitalization among patients with HF.
Topics: Diuretics; Furosemide; Heart Failure; Humans; Multicenter Studies as Topic; Sodium Potassium Chloride Symporter Inhibitors; Torsemide
PubMed: 34936522
DOI: 10.1080/14779072.2022.2022474