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Journal of Cardiovascular Magnetic...Percutaneous-transluminal renal angioplasty (PTRA) and stenting aim to halt the progression of kidney disease in patients with renal artery stenosis (RAS), but its...
BACKGROUND
Percutaneous-transluminal renal angioplasty (PTRA) and stenting aim to halt the progression of kidney disease in patients with renal artery stenosis (RAS), but its outcome is often suboptimal. We hypothesized that a model incorporating markers of renal function and oxygenation extracted using radiomics analysis of blood oxygenation-level dependent (BOLD)-MRI images may predict renal response to PTRA in swine RAS.
MATERIALS AND METHODS
Twenty domestic pigs with RAS were scanned with CT and BOLD MRI before and 4 weeks after PTRA. Stenotic (STK) and contralateral (CLK) kidney volume, blood flow (RBF), and glomerular filtration rate (GFR) were determined, and BOLD-MRI R2 * maps were generated before and after administration of furosemide, a tubular reabsorption inhibitor. Radiomics features were extracted from pre-PTRA BOLD maps and Robust features were determined by Intraclass correlation coefficients (ICC). Prognostic models were developed to predict post-PTRA renal function based on the baseline functional and BOLD-radiomics features, using Lasso-regression for training, and testing with resampling.
RESULTS
Twenty-six radiomics features passed the robustness test. STK oxygenation distribution pattern did not respond to furosemide, whereas in the CLK radiomics features sensitive to oxygenation heterogeneity declined. Radiomics-based model predictions of post-PTRA GFR (r = 0.58, p = 0.007) and RBF (r = 0.68; p = 0.001) correlated with actual measurements with sensitivity and specificity of 92% and 67%, respectively. Models were unsuccessful in predicting post-PTRA systemic measures of renal function.
CONCLUSIONS
Several radiomics features are sensitive to cortical oxygenation patterns and permit estimation of post-PTRA renal function, thereby distinguishing subjects likely to respond to PTRA and stenting.
Topics: Renal Artery Obstruction; Animals; Stents; Predictive Value of Tests; Glomerular Filtration Rate; Disease Models, Animal; Renal Circulation; Sus scrofa; Magnetic Resonance Imaging; Oxygen; Time Factors; Kidney Cortex; Furosemide; Angioplasty, Balloon; Renal Artery; Female; Male; Diuretics; Image Interpretation, Computer-Assisted; Treatment Outcome; Radiomics
PubMed: 38218433
DOI: 10.1016/j.jocmr.2024.100993 -
Diagnostics (Basel, Switzerland) Dec 2023Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the...
Post-Coronary Artery Bypass Grafting Outcomes of Patients with/without Type-2 Diabetes Mellitus and Chronic Kidney Disease Treated with SGLT2 Inhibitor Dapagliflozin: A Single-Center Experience Analysis.
INTRODUCTION
Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease.
AIM
Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD.
MATERIALS AND METHODS
One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM-CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD-CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated.
RESULTS
One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL ( = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L ( = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, = 0.000) and in patients without T2DM (by 73,294 ng/L, = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% ( = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01-6.08% ( = 0.000), T2DM-CKD 7.08-6.04% ( = 0.000), PreD+CKD 5.66-4.98% ( = 0.014), and PreD-CKD 6.03-4.94% ( = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15-87.07%, = 0.000) in the presence of established diabetes and 14.89 (64.75-79.64%, = 0.000) in the prediabetes group.
CONCLUSIONS
Regarding the patients' cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation.
PubMed: 38201325
DOI: 10.3390/diagnostics14010016 -
Cells Dec 2023Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and air. Most cells in the body will assimilate Cd, as its charge and ionic radius... (Review)
Review
Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and air. Most cells in the body will assimilate Cd, as its charge and ionic radius are similar to the essential metals, iron, zinc, and calcium (Fe, Zn, and Ca). Cd preferentially accumulates in the proximal tubular epithelium of the kidney, and is excreted in urine when these cells die. Thus, excretion of Cd reflects renal accumulation (body burden) and the current toxicity of Cd. The kidney is the only organ other than liver that produces and releases glucose into the circulation. Also, the kidney is responsible for filtration and the re-absorption of glucose. Cd is the least recognized diabetogenic substance although research performed in the 1980s demonstrated the diabetogenic effects of chronic oral Cd administration in neonatal rats. Approximately 10% of the global population are now living with diabetes and over 80% of these are overweight or obese. This association has fueled an intense search for any exogenous chemicals and lifestyle factors that could induce excessive weight gain. However, whilst epidemiological studies have clearly linked diabetes to Cd exposure, this appears to be independent of adiposity. This review highlights Cd exposure sources and levels associated with diabetes type 2 and the mechanisms by which Cd disrupts glucose metabolism. Special emphasis is on roles of the liver and kidney, and cellular stress responses and defenses, involving heme oxygenase-1 and -2 (HO-1 and HO-2). From heme degradation, both HO-1 and HO-2 release Fe, carbon monoxide, and a precursor substrate for producing a potent antioxidant, bilirubin. HO-2 appears to have also anti-diabetic and anti-obese actions. In old age, HO-2 deficient mice display a symptomatic spectrum of human diabetes, including hyperglycemia, insulin resistance, increased fat deposition, and hypertension.
Topics: Humans; Animals; Mice; Rats; Cadmium; Obesity; Diabetes Mellitus, Type 2; Hyperglycemia; Glucose
PubMed: 38201287
DOI: 10.3390/cells13010083 -
Pflugers Archiv : European Journal of... Apr 2024The kidney plays a crucial role in acid-base homeostasis. In the distal nephron, α-intercalated cells contribute to urinary acid (H) secretion and β-intercalated cells... (Review)
Review
The kidney plays a crucial role in acid-base homeostasis. In the distal nephron, α-intercalated cells contribute to urinary acid (H) secretion and β-intercalated cells accomplish urinary base (HCO) secretion. β-intercalated cells regulate the acid base status through modulation of the apical Cl/HCO exchanger pendrin (SLC26A4) activity. In this review, we summarize and discuss our current knowledge of the physiological role of the renal transporter AE4 (SLC4A9). The AE4, as cation-dependent Cl/HCO exchanger, is exclusively expressed in the basolateral membrane of β-intercalated cells and is essential for the sensing of metabolic acid-base disturbances in mice, but not for renal sodium reabsorption and plasma volume control. Potential intracellular signaling pathways are discussed that might link basolateral acid-base sensing through the AE4 to apical pendrin activity.
Topics: Animals; Mice; Chloride-Bicarbonate Antiporters; Kidney; Kidney Tubules, Collecting
PubMed: 38195948
DOI: 10.1007/s00424-023-02899-5 -
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 -
Communications Biology Jan 2024Torpor and arousal cycles, both daily and seasonal (e.g. hibernation), are crucial for small mammals, including bats, to maintain the energy and water balance. The...
Torpor and arousal cycles, both daily and seasonal (e.g. hibernation), are crucial for small mammals, including bats, to maintain the energy and water balance. The alternation between torpor and arousal leads to metabolic changes, leaving traceable evidence of metabolic wastes in urine. In this study we investigated urinary creatinine and acetoacetate (a ketone body) in the Eastern bent-wing bat (Miniopterus fuliginosus) in Mungyeong, South Korea. We found an increase in urinary creatinine during torpor in summer, indicating changes in renal water reabsorption rates during the active season. Although we could not confirm ketonuria in hibernating bats due to a methodological limitation caused by the small amount of urine, we verified an increase in urinary creatinine concentration during hibernation. This finding suggests that managing water stress resulting from evaporative water loss is one of key reasons for arousal during hibernation in Eastern bent-wing bats.
Topics: Animals; Hibernation; Chiroptera; Creatinine; Torpor; Republic of Korea
PubMed: 38182741
DOI: 10.1038/s42003-023-05713-1 -
Uptake of Fluorescein via a pH-Dependent Monocarboxylate Transporter by Human Kidney 2 (HK-2) Cells.Biological & Pharmaceutical Bulletin 2024Herein, we investigated whether a fluorescent probe for an organic anion transporter (OAT), fluorescein (FLS), could be accumulated by human kidney 2 (HK-2) cells...
Herein, we investigated whether a fluorescent probe for an organic anion transporter (OAT), fluorescein (FLS), could be accumulated by human kidney 2 (HK-2) cells derived from human kidney proximal tubular epithelia. HK-2 cells took up FLS in a pH-dependent and concentration-dependent manner. FLS accumulation by HK-2 cells was inhibited by monocarboxylic acids, ibuprofen, rosuvastatin, and indoleacetic acid but not by typical substrates for OATs. A typical protonophore, carbonyl cyanide p-trichloromethoxyphenylhydrazone completely abolished FLS accumulation by HK-2 cells. The FLS efflux process from the preloaded HK-2 cells exhibited substantial trans-stimulation by the excess amount of extracellular FLS transport inhibitable monocarboxylate compounds such as 2,4-dichloro phenoxyacetic acid, fluvastatin, ibuprofen, indoleacetic acid, salicylic acid and rosuvastatin, indicating that the FLS transporter can recognize and accumulate them into the cells in a pH-dependent manner. The involvement of the FLS transporter in the reabsorption of monocarboxylic compounds was indicated by demonstrating that the pH-dependent FLS uptake is inhibited by various monocarboxylates in rabbit renal brush border membrane vesicles. pH-dependent FLS uptake was trans-stimulated by the inhibitable monocarboxylates. Collectively, the present data indicate that the pH-dependent transporters expressed in HK-2 cells are involved in the reabsorption of monocarboxylates from the urinary fluid into the tubular epithelia.
Topics: Animals; Humans; Rabbits; Fluorescein; Ibuprofen; Rosuvastatin Calcium; Monocarboxylic Acid Transporters; Kidney; Biological Transport; Indoleacetic Acids; Hydrogen-Ion Concentration
PubMed: 38171781
DOI: 10.1248/bpb.b23-00570 -
Endocrinology and Metabolism (Seoul,... Feb 2024Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for...
BACKGRUOUND
Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states.
METHODS
Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco's modified Eagle's medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours.
RESULTS
SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation.
CONCLUSION
These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.
Topics: Humans; AMP-Activated Protein Kinases; Diabetes Mellitus, Type 2; Gluconeogenesis; Glucose; Phosphoenolpyruvate Carboxykinase (ATP); Proto-Oncogene Proteins c-akt; RNA, Small Interfering; Signal Transduction; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38171209
DOI: 10.3803/EnM.2023.1786 -
The Journal of Physiological Sciences :... Jan 2024In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney is tightly regulated by reabsorption and secretion. At least eleven...
In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney is tightly regulated by reabsorption and secretion. At least eleven genes have been identified as human renal urate transporters. However, it remains unclear whether all renal tubular cells express the same set of urate transporters. Here, we show renal tubular cells are divided into three distinct cell populations for urate handling. Analysis of healthy human kidneys at single-cell resolution revealed that not all tubular cells expressed the same set of urate transporters. Only 32% of tubular cells were related to both reabsorption and secretion, while the remaining tubular cells were related to either reabsorption or secretion at 5% and 63%, respectively. These results provide physiological insight into the molecular function of the transporters and renal urate handling on single-cell units. Our findings suggest that three different cell populations cooperate to regulate urate excretion from the human kidney, and our proposed framework is a step forward in broadening the view from the molecular to the cellular level of transport capacity.
Topics: Humans; Uric Acid; Kidney; Biological Transport
PubMed: 38166558
DOI: 10.1186/s12576-023-00894-0 -
British Journal of Hospital Medicine... Dec 2023Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect...
Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, leading to hypocalciuria. The effect that thiazide diuretics exert on parathyroid hormone secretion is controversial. Some studies found parathyroid hormone levels were suppressed with the use of thiazide diuretics, while others found that thiazides were associated with initial parathyroid hormone suppression followed by raised parathyroid hormone levels. This makes the relationship between thiazide diuretics and primary hyperparathyroidism interesting. If a patient is taking thiazide diuretics, this may make it harder to establish the aetiology of hypercalcaemia and may unmask normocalcaemic or mild primary hyperparathyroidism. Thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism. In addition, thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery.
Topics: Humans; Sodium Chloride Symporter Inhibitors; Calcium; Hyperparathyroidism, Primary; Hypercalciuria; Diuretics; Parathyroid Hormone
PubMed: 38153014
DOI: 10.12968/hmed.2023.0228